Flow dependence of forearm noradrenaline overflow, as assessed during mental stress and sodium nitroprusside infusion.

PubMed

Lindqvist, M; Melcher, A; Hjemdahl, P

1999-01-01

To evaluate the influence of blood flow on measurements of regional sympathetic nerve activity by radiotracer methodology ([3H]noradrenaline). Ten healthy men were studied under two conditions of elevated forearm blood flow: mental stress (Stroop colour word conflict test) and an intra-arterial infusion of sodium nitroprusside. Arterial blood pressure was measured invasively and forearm blood flow with strain-gauge plethysmography. Arterial and venous plasma adrenaline and noradrenaline were measured with high-performance liquid chromatography, and regional and total noradrenaline spillover were calculated. During mental stress, mean arterial pressure increased by 17%, heart rate by 16 beats/min, forearm blood flow by 117%, while forearm vascular resistance decreased by 44% (P < 0.001 for all). Sodium nitroprusside increased forearm blood flow dose-dependently, but elicited only minor effects on systemic haemodynamics. Mental stress increased arterial plasma noradrenaline by 52% (P < 0.001), and total body noradrenaline spillover by 75% (P < 0.001). During sodium nitroprusside infusion, arterial plasma noradrenaline increased only slightly and total body noradrenaline spillover was unaffected Forearm noradrenaline overflow increased from 5.4 +/- 0.9 to 16.9 +/- 2.6 pmol/min per I (P < 0.001) during mental stress and from 6.6 +/- 0.8 to 16.9 +/- 3.7 pmol/min per I (P < 0.001) during the second dose-step of sodium nitroprusside infusion. By intra-individual comparisons of forearm noradrenaline overflow increases during mental stress and during sodium nitroprusside infusion, with similar forearm blood flow increases, the flow dependence of forearm noradrenaline overflow was estimated. During mental stress, about 60% (median value, range 29-112%) of the increase in forearm noradrenaline overflow was attributed to the increase in forearm blood flow, whereas 40% was considered to reflect increased sympathetic nerve activity. There seems to be a considerable flow dependence of the regional overflow of noradrenaline, that is, a component of simple wash-out of noradrenaline from the forearm tissues during vasodilation. However, the present results still indicate that sympathetic nerve activity in the forearm is increased during mental stress, justifying the radiotracer technique for semiquantitative measurements, also during vasodilation.

Afferent vagal stimulation, vasopressin, and nitroprusside alter cerebrospinal fluid kinin.

PubMed

Thomas, G R; Thibodeaux, H; Margolius, H S; Webb, J G; Privitera, P J

1987-07-01

The effects of afferent vagal stimulation, cerebroventricular vasopressin, and intravenous nitroprusside on cerebrospinal fluid (CSF) kinin levels, mean arterial pressure (MAP), and heart rate (HR) were determined in anesthetized dogs in which a ventriculocisternal perfusion system (VP) was established. Following bilateral vagotomy, stimulation of the central ends of both vagi for 60 min significantly increased MAP and CSF perfusate levels of kinin and norepinephrine (NE). MAP was increased a maximum of 32 +/- 4 mmHg, and the rates of kinin and NE appearance into the CSF perfusate increased from 4.2 +/- 1.4 to 22.1 +/- 6.9 and from 28 +/- 5 to 256 +/- 39 pg/min, respectively. A significant correlation was found between CSF kinin and NE levels in these experiments. In other experiments the addition of arginine vasopressin to the VP system caused a significant increase in CSF perfusate kinin without affecting MAP or HR. Intravenous infusion of nitroprusside lowered MAP without affecting kinin levels in the CSF. However, on cessation of nitroprusside infusion, CSF kinin increased significantly in association with the return in MAP to predrug level. Collectively the data are consistent with the hypothesis that central nervous system kinins have some role in cardiovascular regulation, and furthermore that this role may involve an interaction between brain kinin and central noradrenergic neuronal pathways.

Ventilatory effects of substance P, vasoactive intestinal peptide, and nitroprusside in humans.

PubMed

Maxwell, D L; Fuller, R W; Dixon, C M; Cuss, F M; Barnes, P J

1990-01-01

Animal studies suggest that the neuropeptides, substance P and vasoactive intestinal peptide (VIP), may influence carotid body chemoreceptor activity and that substance P may take part in the carotid body response to hypoxia. The effects of these peptides on resting ventilation and on ventilatory responses to hypoxia and to hypercapnia have been investigated in six normal humans. Infusions of substance P (1 pmol.kg-1.min-1) and of VIP (6 pmol.kg-1.min-1) were compared with placebo and with nitroprusside (5 micrograms.kg-1.min-1) as a control for the hypotensive action of the peptides. Both peptides caused significantly less hypotension than nitroprusside. Substance P and nitroprusside caused significantly greater increases in ventilation and in the hypoxic ventilatory response than VIP. No changes were seen in hypercapnic sensitivity. The stimulation of ventilation and the differential effects on ventilatory chemosensitivity that accompanied hypotension are consistent either with stimulation of carotid body chemoreceptor activity or with an interaction with peripheral chemoreceptor input to the respiratory center, as is seen in animals. The similar cardiovascular but different ventilatory effects of the peptides suggest that substance P may also stimulate the carotid body in a manner independent of the effect of hypotension. This is consistent with a role of substance P in the hypoxic ventilatory response in humans.

[The effects of sildenafil citrate on the isolated rat aorta: comparative in vitro study].

PubMed

Ozbek, H; Güler, N; Aydin, S; Eryonucu, B; Bilge, M

2001-03-01

Sildenafil, an inhibitor of cGMP-specific phosphodiesterase 5 (PDE5), is currently being used as oral therapy for penile erectile dysfunction. The aim of this study was to investigate the relaxing effect of sildenafil on vascular tissue and compare it with the known vasodilatator agents, sodium nitroprusside and acetylcholine. Rat thoracic aorta samples were cut into rings, mounted on steel hooks, and immersed in aerated Krebs solution maintained at 37 degree C. Isometric responses were recorded by strain gauge transducers connected to a polygraph. Graded relaxations were induced using increasing concentrations of acetylcholine sodium nitroprusside and sildenafil. The agents all does-dependently relaxed rat aorta strips. The relaxing potential of sildenafil was found to be similar to sodium nitroprusside, but higher than acetylcholine. In the absence of regulatory mechanisms, sildenafil citrate has noticeable vasodilatatory effect in vitro.

Inhibition by sodium nitroprusside of the expression of inducible nitric oxide synthase in rat neutrophils.

PubMed Central

Mariotto, S; Cuzzolin, L; Adami, A; Del Soldato, P; Suzuki, H; Benoni, G

1995-01-01

A well-known nitric oxide (NO)-releasing compound, sodium nitroprusside (SNP), decreases in a dose-dependent manner NO synthase (NOS) activity induced in rat neutrophils by treatment with lipopolysaccharide (LPS). This inhibitory action of SNP seems not to be due to its direct effect on the enzyme activity. The strong nitrosonium ion (NO+) character of SNP could be responsible for its inhibition of NOS induction in neutrophils. PMID:7542530

Study of carbon dioxide adsorption on a Cu-nitroprusside polymorph

DOE PAGES

Roque-Malherbe, R.; Lozano, C.; Polanco, R.; ...

2011-03-26

A careful structural characterization was carried out to unequivocally determine the structure of the synthesized material. The TGA, DRIFTS and a Pawley fitting of the XRD powder profiles indicate that the hydrated and in situ dehydrated polymorph crystallizes in the orthorhombic space group Pnma. Meanwhile, the CO 2 isosteric heat of adsorption appears to be independent of loading with an average value of 30 kJ/mol. This translates to a physisorption type interaction, where the adsorption energy corresponding to wall and lateral interactions are mutually compensated to produce, an apparently, homogeneous adsorption energy. The somewhat high adsorption energy is probably duemore » to the confinement of the CO 2 molecules in the nitroprusside pores. Statistical Physics and the Dubinin theory for pore volume filling allowed model the CO 2 equilibrium adsorption process in Cu-nitroprusside. A DRIFTS test for the adsorbed CO 2 displayed a peak at about 2338 cm -1 that was assigned to a contribution due to physical adsorption of the molecule. Another peak found at 2362 cm -1 evidenced that this molecule interacts with the Cu 2+, which appears to act as an electron accepting Lewis acid site. In conclusion, the aim of the present paper is to report a Pnma stable Cu-nitroprusside polymorph obtained by the precipitation method that can adsorb carbon dioxide.« less

Antioxidant properties of aqueous extracts of unripe Musa paradisiaca on sodium nitroprusside induced lipid peroxidation in rat pancreas in vitro.

PubMed

Shodehinde, Sidiqat Adamson; Oboh, Ganiyu

2013-06-01

To evaluate and compare antioxidant activities of the aqueous extracts of unripe plantain (Musa paradisiaca), assess their inhibitory action on sodium nitroprusside induced lipid peroxidation in rat pancreas in vitro and to characterize the main phenolic constituents of the plantain products using gas chromatography analysis. Aqueous extracts of plantain products (raw, elastic pastry, roasted and boiled) flour of 0.1 g/mL (each) were used to determine their total phenol, total flavonoid, 1,1 diphenyl-2 picrylhydrazyl (DPPH) and hydroxyl (OH) radical scavenging ability. The inhibitory effect of the extracts on sodium nitroprusside induced lipid peroxidation was also determined. The results revealed that all the aqueous extracts showed antioxidant activity. The boiled flour had highest DPPH and OH radical scavenging ability while raw flour had the highest Fe(2+) chelating ability, sodium nitroprusside inhibitory effect and vitamin C content. The antioxidant results showed that elastic pastry had the highest total phenol and total flavonoid content. Characterization of the unripe plantain products for polyphenol contents using gas chromatography showed varied quantity of apigenin, myricetin, luteolin, capsaicin, isorhaemnetin, caffeic acid, kampferol, quercetin, p-hydroxybenzoic acid, shogaol, glycitein and gingerol per product on the spectra. Considering the antioxidant activities and ability to inhibit lipid peroxidation of unripe plantain, this could justify their traditional use in the management/prevention of diseases related to stress.

Antioxidant properties of aqueous extracts of unripe Musa paradisiaca on sodium nitroprusside induced lipid peroxidation in rat pancreas in vitro

PubMed Central

Shodehinde, Sidiqat Adamson; Oboh, Ganiyu

2013-01-01

Objective To evaluate and compare antioxidant activities of the aqueous extracts of unripe plantain (Musa paradisiaca), assess their inhibitory action on sodium nitroprusside induced lipid peroxidation in rat pancreas in vitro and to characterize the main phenolic constituents of the plantain products using gas chromatography analysis. Methods Aqueous extracts of plantain products (raw, elastic pastry, roasted and boiled) flour of 0.1 g/mL (each) were used to determine their total phenol, total flavonoid, 1,1 diphenyl-2 picrylhydrazyl (DPPH) and hydroxyl (OH) radical scavenging ability. The inhibitory effect of the extracts on sodium nitroprusside induced lipid peroxidation was also determined. Results The results revealed that all the aqueous extracts showed antioxidant activity. The boiled flour had highest DPPH and OH radical scavenging ability while raw flour had the highest Fe2+ chelating ability, sodium nitroprusside inhibitory effect and vitamin C content. The antioxidant results showed that elastic pastry had the highest total phenol and total flavonoid content. Characterization of the unripe plantain products for polyphenol contents using gas chromatography showed varied quantity of apigenin, myricetin, luteolin, capsaicin, isorhaemnetin, caffeic acid, kampferol, quercetin, p-hydroxybenzoic acid, shogaol, glycitein and gingerol per product on the spectra. Conclusions Considering the antioxidant activities and ability to inhibit lipid peroxidation of unripe plantain, this could justify their traditional use in the management/prevention of diseases related to stress. PMID:23730557

Nitric oxide alleviates wheat yield reduction by protecting photosynthetic system from oxidation of ozone pollution.

PubMed

Li, Caihong; Song, Yanjie; Guo, Liyue; Gu, Xian; Muminov, Mahmud A; Wang, Tianzuo

2018-05-01

Accelerated industrialization has been increasing releases of chemical precursors of ozone. Ozone concentration has risen nowadays, and it's predicted that this trend will continue in the next few decades. The yield of many ozone-sensitive crops suffers seriously from ozone pollution, and there are abundant reports exploring the damage mechanisms of ozone to these crops, such as winter wheat. However, little is known on how to alleviate these negative impacts to increase grain production under elevated ozone. Nitric oxide, as a bioactive gaseous, mediates a variety of physiological processes and plays a central role in response to biotic and abiotic stresses. In the present study, the accumulation of endogenous nitric oxide in wheat leaves was found to increase in response to ozone. To study the functions of nitric oxide, its precursor sodium nitroprusside was spayed to wheat leaves under ozone pollution. Wheat leaves spayed with sodium nitroprusside accumulated less hydrogen peroxide, malondialdehyde and electrolyte leakage under ozone pollution, which can be accounted for by the higher activities of superoxide dismutase and peroxidase than in leaves treated without sodium nitroprusside. Consequently, net photosynthetic rate of wheat treated using sodium nitroprusside was much higher, and yield reduction was alleviated under ozone fumigation. These findings are important for our understanding of the potential roles of nitric oxide in responses of crops in general and wheat in particular to ozone pollution, and provide a viable method to mitigate the detrimental effects on crop production induced by ozone pollution, which is valuable for keeping food security worldwide. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nitric oxide donors, sodium nitroprusside and S-nitroso-N-acetylpencillamine, stimulate myoblast proliferation in vitro

NASA Technical Reports Server (NTRS)

Ulibarri, J. A.; Mozdziak, P. E.; Schultz, E.; Cook, C.; Best, T. M.

1999-01-01

Nitric oxide (NO) is an inter- and intracellular messenger involved in a variety of physiologic and pathophysiologic conditions. The effect of two NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) and their effect on myoblast proliferation was examined. Both donors stimulated an increase in myoblast cell number over a range (1-10 microM) of donor concentrations. However, 50 microM SNAP inhibited myoblast proliferation. Cell numbers from cultures treated with degraded 10 microM SNAP were equivalent to the control. Therefore, it appears NO can stimulate as well as inhibit myoblast proliferation.

Effect of nitrofurans and NO generators on biofilm formation by Pseudomonas aeruginosa PAO1 and Burkholderia cenocepacia 370.

PubMed

Zaitseva, Julia; Granik, Vladimir; Belik, Alexandr; Koksharova, Olga; Khmel, Inessa

2009-06-01

Antibacterial drugs in the nitrofuran series, such as nitrofurazone, furazidin, nitrofurantoin and nifuroxazide, as well as the nitric oxide generators sodium nitroprusside and isosorbide mononitrate in concentrations that do not suppress bacterial growth, were shown to increase the capacity of pathogenic bacteria Pseudomonas aeruginosa PAO1 and Burkholderia cenocepacia 370 to form biofilms. At 25-100microg/ml, nitrofurans 2-2.5-fold enhanced biofilm formation of P. aeruginosa PAO1, and NO donors 3-6-fold. For B. cenocepacia 370, the enhancement was 2-5-fold (nitrofurans) and 4.5-fold (sodium nitroprusside), respectively.

Nitric oxide inhibits calpain-mediated proteolysis of talin in skeletal muscle cells

NASA Technical Reports Server (NTRS)

Koh, T. J.; Tidball, J. G.

2000-01-01

We tested the hypothesis that nitric oxide can inhibit cytoskeletal breakdown in skeletal muscle cells by inhibiting calpain cleavage of talin. The nitric oxide donor sodium nitroprusside prevented many of the effects of calcium ionophore on C(2)C(12) muscle cells, including preventing talin proteolysis and release into the cytosol and reducing loss of vinculin, cell detachment, and loss of cellular protein. These results indicate that nitric oxide inhibition of calpain protected the cells from ionophore-induced proteolysis. Calpain inhibitor I and a cell-permeable calpastatin peptide also protected the cells from proteolysis, confirming that ionophore-induced proteolysis was primarily calpain mediated. The activity of m-calpain in a casein zymogram was inhibited by sodium nitroprusside, and this inhibition was reversed by dithiothreitol. Previous incubation with the active site-targeted calpain inhibitor I prevented most of the sodium nitroprusside-induced inhibition of m-calpain activity. These data suggest that nitric oxide inhibited m-calpain activity via S-nitrosylation of the active site cysteine. The results of this study indicate that nitric oxide produced endogenously by skeletal muscle and other cell types has the potential to inhibit m-calpain activity and cytoskeletal proteolysis.

Nitric oxide donor augments antineoplastic effects of arginine deprivation in human melanoma cells.

PubMed

Mayevska, Oksana; Chen, Oleh; Karatsai, Olena; Bobak, Yaroslav; Barska, Maryna; Lyniv, Liliana; Pavlyk, Iuliia; Rzhepetskyy, Yuriy; Igumentseva, Natalia; Redowicz, Maria Jolanta; Stasyk, Oleh

2017-06-15

Anticancer therapy based on recombinant arginine-degrading enzymes has been proposed for the treatment of several types of malignant cells deficient in arginine biosynthesis. One of the predicted side effects of such therapy is restricted bioavailability of nitric oxide as arginine catabolic product. Prolonged NO limitation may lead to unwanted disturbances in NO-dependent vasodilation, cardiovascular and immune systems. This problem can be overcome by co-supplementation with exogenous NO donor. However, NO may potentially counteract anticancer effects of therapy based on arginine deprivation. In this study, we evaluate for the first time the effects of an exogenous NO donor, sodium nitroprusside, on viability and metastatic properties of two human melanoma cell lines SK-MEL-28 and WM793 under arginine-deprived conditions. It was revealed that NO did not rescue melanoma cells from specific effects evoked by arginine deprivation, namely decreased viability and induction of apoptosis, dramatically reduced motility, invasiveness and clonogenic potential. Moreover, sodium nitroprusside co-treatment augmented several of these antineoplastic effects. We report that a combination of NO-donor and arginine deprivation strongly and specifically impaired metastatic behavior of melanoma cells. Thus, sodium nitroprusside can be considered as an adjuvant for the more efficient treatment of malignant melanoma and possibly other tumors with arginine-degrading enzymes. Copyright © 2017 Elsevier Inc. All rights reserved.

Evidence against nitrergic neuromodulation in the rat vas deferens.

PubMed

Ventura, S; Burnstock, G

1997-09-03

Electrical field stimulation (60 V, 1 ms, single pulses or 20 s trains of 1-10 Hz) of the nerve terminals within the rat vas deferens produced biphasic contractions in preparations oriented to measure either longitudinal or circular muscle contractions. In confirmation of earlier reports, these contractions were blocked by tetrodotoxin (1 microM). The initial fast purinergic contraction was dominant in prostatic halves of the vas deferens while the second slower noradrenergic contraction was greater in epididymal halves. Although previous studies have shown nitric oxide synthase immuno-positive nerves in the vas deferens, electrical field stimulation-induced contractions were unaffected by L-arginine, sodium nitroprusside, N-nitro-L-arginine methyl ester (L-NAME) or superoxide dismutase in concentrations up to I mM. In concentrations above 1 mM, L-NAME reduced the size of the field stimulation-induced contractions but this effect could not be reversed by either L-arginine or sodium nitroprusside. Furthermore, L-arginine, sodium nitroprusside and L-NAME did not affect the contractions induced by exogenous application of noradrenaline (10 microM), ATP (1 mM) or BaCl2 (1-10 mM). We conclude that nitric oxide does not act as a neuromodulator in isolated preparations of rat vas deferens.

Effect of nitroso complexes of some transition metals on the activity of soluble guanylate cyclase.

PubMed

Severina, I S; Bussygina, O G; Grigorjev, N B

1992-03-01

Effects of nitroso complexes of some transition metals (Fe, Co, Cr), differing in the character of NO oxidation on the activity of human and rat platelet guanylate cyclase were studied. 3 types of nitroso complexes were used: (1) NO group carries a positive charge--a nitrosonium cation (Na2[FeNO + (CN)5]-nitroprusside); (2) NO is neutral--(K3[CrNO(CN)5 and [CoNO(NH3)5]SO4) and (3) NO is coordinated as anion NO- (K3[CoNO-(CN)5]. It is shown that the highest stimulatory effect is produced by sodium nitroprusside, whose activating action is due to the interaction of its NO group with the guanylate cyclase heme. Nitroso complexes (Co and Cr) the NO group of which is neutral stimulated guanylate cyclase activity insignificantly and this activation was not guanylate cyclase heme directed. Nitroso complex (Co) with NO coordinated as anion NO(-)--is a guanylate cyclase inhibitor. In contrast to nitroprusside, the nitroso complexes used (Co and Cr) have no hypotensive effect. It was concluded that the essential requirement for the realization of the hypotensive effect of transition metals' nitroso complexes is the ability of these compounds to activate soluble guanylate cyclase solely by the heme-dependent mechanism.

Low-Renin Hypertension With Relative Aldosterone Excess Is Associated With Impaired NO-Mediated Vasodilation

PubMed Central

Duffy, Stephen J.; Biegelsen, Elizabeth S.; Eberhardt, Robert T.; Kahn, David F.; Kingwell, Bronwyn A.; Vita, Joseph A.

2009-01-01

Recent studies suggest that hypertension associated with low renin status and hyperaldosteronism is associated with increased risk for end-organ damage and cardiovascular events compared with other forms of hypertension. Additionally, experimental studies have demonstrated impaired nitric oxide-mediated bioactivity in these states. To investigate the relation between renin/aldosterone status and resistance vessel function, we examined plasma renin activity, serum aldosterone level, and forearm blood flow responses to the endothelium-dependent vasodilator methacholine and the endothelium-independent vasodilators sodium nitroprusside and verapamil using venous occlusion plethysmography in 130 volunteers (43 hypertensive, 87 normotensive). Low renin status was associated with impaired responses to methacholine and nitroprusside in patients with hypertension. Peak methacholine response was 8.7±5.6 mL/min per dL in the lowest renin quartile (0.1 to 0.3 ng/mL per hour) versus 14.3±7.3 mL/min per dL in the highest 3 renin quartiles combined (0.4 to 4.6 ng/mL per hour; P<0.001). Peak nitroprusside response was 5.6±2.3 mL/min per dL in the lowest renin quartile versus 13.3±4.1 mL/min per dL in the highest 3 renin quartiles combined (P<0.001). Blood pressure and other clinical characteristics were similar in all 4 quartiles. Vasodilator responses to verapamil did not relate to renin activity. Methacholine and nitroprusside responses did not relate to renin status in normotensive controls (P=0.34). Importantly, hypertensive patients with a high aldosterone/renin ratio also had impaired responses to methacholine. This study demonstrates that low-renin hypertension is associated with marked impairment of nitric oxide-mediated vasodilation of resistance vessels in the forearm vasculature of humans. This impairment could contribute to adverse outcomes in patients with low-renin hypertension and relative aldosterone excess. PMID:16172426

Lipid Emulsion Attenuates Acetylcholine-Induced Relaxation in Isolated Rat Aorta

PubMed Central

Ok, Seong-Ho; Lee, Soo Hee; Yu, Jongsun; Park, Jungchul; Shin, Il-Woo; Lee, Youngju; Cho, Hyunhoo; Choi, Mun-Jeoung; Baik, Jiseok; Hong, Jeong-Min; Han, Jeong Yeol; Lee, Heon Keun; Chung, Young-Kyun; Sohn, Ju-Tae

2015-01-01

We investigated the effect of Lipofundin MCT/LCT and Intralipid on acetylcholine-induced nitric oxide- (NO-) mediated relaxation in rat aorta to determine which lipid emulsion (LE) is more potent in terms of inhibition of NO-induced relaxation. Dose-response curves of responses induced by acetylcholine, the calcium ionophore A23187, and sodium nitroprusside were generated using isolated rat aorta with or without LE. The effect of Lipofundin MCT/LCT on acetylcholine-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells (HUVECs) was investigated using western blotting. Lipofundin MCT/LCT (0.1 and 0.2%) attenuated acetylcholine-induced relaxation in endothelium-intact aorta with or without tiron, whereas 0.2% Intralipid only inhibited relaxation. Lipofundin MCT/LCT inhibited relaxation induced by the calcium ionophore A23187 and sodium nitroprusside in endothelium-intact aorta, but Lipofundin MCT/LCT had no effect on sodium nitroprusside-induced relaxation in the endothelium-denuded aorta. Combined pretreatment with l-arginine plus Lipofundin MCT/LCT increased acetylcholine-induced maximal relaxation in endothelium-intact aorta compared with Lipofundin MCT/LCT alone. l-Arginine attenuated Lipofundin MCT/LCT-mediated inhibition of acetylcholine-induced eNOS phosphorylation in HUVECs. Taken together, Lipofundin MCT/LCT attenuated acetylcholine-induced NO-mediated relaxation via an inhibitory effect on the endothelium including eNOS, which is proximal to activation of guanylyl cyclase. PMID:26273653

Lipid Emulsion Attenuates Acetylcholine-Induced Relaxation in Isolated Rat Aorta.

PubMed

Ok, Seong-Ho; Lee, Soo Hee; Yu, Jongsun; Park, Jungchul; Shin, Il-Woo; Lee, Youngju; Cho, Hyunhoo; Choi, Mun-Jeoung; Baik, Jiseok; Hong, Jeong-Min; Han, Jeong Yeol; Lee, Heon Keun; Chung, Young-Kyun; Sohn, Ju-Tae

2015-01-01

We investigated the effect of Lipofundin MCT/LCT and Intralipid on acetylcholine-induced nitric oxide- (NO-) mediated relaxation in rat aorta to determine which lipid emulsion (LE) is more potent in terms of inhibition of NO-induced relaxation. Dose-response curves of responses induced by acetylcholine, the calcium ionophore A23187, and sodium nitroprusside were generated using isolated rat aorta with or without LE. The effect of Lipofundin MCT/LCT on acetylcholine-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells (HUVECs) was investigated using western blotting. Lipofundin MCT/LCT (0.1 and 0.2%) attenuated acetylcholine-induced relaxation in endothelium-intact aorta with or without tiron, whereas 0.2% Intralipid only inhibited relaxation. Lipofundin MCT/LCT inhibited relaxation induced by the calcium ionophore A23187 and sodium nitroprusside in endothelium-intact aorta, but Lipofundin MCT/LCT had no effect on sodium nitroprusside-induced relaxation in the endothelium-denuded aorta. Combined pretreatment with l-arginine plus Lipofundin MCT/LCT increased acetylcholine-induced maximal relaxation in endothelium-intact aorta compared with Lipofundin MCT/LCT alone. L-Arginine attenuated Lipofundin MCT/LCT-mediated inhibition of acetylcholine-induced eNOS phosphorylation in HUVECs. Taken together, Lipofundin MCT/LCT attenuated acetylcholine-induced NO-mediated relaxation via an inhibitory effect on the endothelium including eNOS, which is proximal to activation of guanylyl cyclase.

Ketones blood test

MedlinePlus

Acetone bodies; Ketones - serum; Nitroprusside test; Ketone bodies - serum; Ketones - blood; Ketoacidosis - ketones blood test ... fat cells break down in the blood. This test is used to diagnose ketoacidosis . This is a ...

[Effect of glutamate on membrane potential and volume of the skeletal muscle fibers in rats following NO-synthase inhibition in vivo].

PubMed

Khairova, P A; Malomuzh, A I; Naumenko, N V; Urazaev, A Kh

2002-11-01

Cross-sectional area (CSA) of muscle fibers incubated in culture medium 199 for 3 hours dramatically increases, whereas resting membrane potential (RMP) decreases compared to "freshly-isolated" muscles. Both glutamate and sodium nitroprusside prevent these changes. MK-801, a specific inhibitor of NMDA-receptors, eliminates protective effects of glutamate on both CSA and RMP. NO-synthase inhibition in vivo promotes an increase of initial CSA and decrease of mean RMP. Under these conditions, effects of glutamate and sodium nitroprusside on CSA and RMP of denervated muscles are less obvious. It has been concluded that synaptic glutamate is able to participate in regulation of RMP and cell volume in muscle fibers through the activation of postsynaptic NMDA-receptors and muscle NO-synthase.

Autonomic Blockade Reverses Endothelial Dysfunction in Obesity-Associated Hypertension.

PubMed

Gamboa, Alfredo; Figueroa, Rocío; Paranjape, Sachin Y; Farley, Ginnie; Diedrich, Andre; Biaggioni, Italo

2016-10-01

Impaired nitric oxide (NO) vasodilation (endothelial dysfunction) is associated with obesity and thought to be a factor in the development of hypertension. We previously found that NO synthesis inhibition had similar pressor effects in obese hypertensives compared with healthy control during autonomic blockade, suggesting that impaired NO vasodilation is secondary to sympathetic activation. We tested this hypothesis by determining the effect of autonomic blockade (trimethaphan 4 mg/min IV) on NO-mediated vasodilation (increase in forearm blood flow to intrabrachial acetylcholine) compared with endothelial-independent vasodilation (intrabrachial sodium nitroprusside) in obese hypertensive subjects (30

Blood pressure and mesenteric resistance arterial function after spaceflight

NASA Technical Reports Server (NTRS)

Hatton, Daniel C.; Yue, Qi; Chapman, Justin; Xue, Hong; Dierickx, Jacqueline; Roullet, Chantal; Coste, Sarah; Roullet, Jean Baptiste; McCarron, David A.

2002-01-01

Ground studies indicate that spaceflight may diminish vascular contraction. To examine that possibility, vascular function was measured in spontaneously hypertensive rats immediately after an 18-day shuttle flight. Isolated mesenteric resistance arterial responses to cumulative additions of norepinephrine, acetylcholine, and sodium nitroprusside were measured using wire myography within 17 h of landing. After flight, maximal contraction to norepinephrine was attenuated (P < 0.001) as was relaxation to acetylcholine (P < 0.001) and sodium nitroprusside (P < 0.05). At high concentrations, acetylcholine caused vascular contraction in vessels from flight animals but not in vessels from vivarium control animals (P < 0.05). The results are consistent with data from ground studies and indicate that spaceflight causes both endothelial-dependent and endothelial-independent alterations in vascular function. The resulting decrement in vascular function may contribute to orthostatic intolerance after spaceflight.

Blockade of beta-adrenoceptors enhances cAMP signal transduction in vivo

NASA Technical Reports Server (NTRS)

Whalen, E. J.; Johnson, A. K.; Lewis, S. J.

1998-01-01

The aim of this study was to determine whether the blockade of beta-adrenoceptors would enhance cAMP-mediated signal transduction processes in vivo. The administration of the membrane permeable cAMP analogue, 8-(4-chlorophenylthiol)-cAMP (8-CPT-cAMP, 10 micromol/kg, i.v.) produced an increase in heart rate (+27 +/- 2%, P < 0.05), a fall in mean arterial blood pressure (-21 +/- 3%, P < 0.05) and falls in hindquarter (-12 +/- 3%, P < 0.05) and mesenteric (-32 +/- 3%, P < 0.05) vascular resistances in pentobarbital-anesthetized rats. The beta-adrenoceptor antagonist, propranolol (1 mg/kg, i.v.) lowered heart rate (-12 +/- 3%, P < 0.05) but did not affect mean arterial blood pressure or vascular resistances. The tachycardia, hypotension and vasodilation produced by 8-CPT-cAMP were exaggerated after administration of propranolol (P < 0.05 for all comparisons). The nitric oxide-donor, sodium nitroprusside (2 microg/kg, i.v.), produced falls in mean arterial blood pressure and vascular resistances of similar magnitude to those produced by 8-CPT-cAMP. These sodium nitroprusside-induced responses were unaffected by propranolol (P < 0.05 for all comparisons). Sodium nitroprusside also produced a minor increase in heart rate (+5 +/- 1%, P < 0.05) which was abolished by propranolol. These findings suggest that 8-CPT-cAMP directly increases heart rate and that blockade of beta-adrenoceptors enhances the potency of cAMP within the heart and vasculature.

Low abundance of mitochondrial DNA changes mitochondrial status and renders cells resistant to serum starvation and sodium nitroprusside insult.

PubMed

Lee, Sung Ryul; Heo, Hye Jin; Jeong, Seung Hun; Kim, Hyoung Kyu; Song, In Sung; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Nari; Han, Jin

2015-07-01

Mutation or depletion of mitochondrial DNA (mtDNA) can cause severe mitochondrial malfunction, originating from the mitochondrion itself, or from the crosstalk between nuclei and mitochondria. However, the changes that would occur if the amount of mtDNA is diminished are less known. Thus, we generated rat myoblast H9c2 cells containing lower amounts of mtDNA via ethidium bromide and uridine supplementation. After confirming the depletion of mtDNA by quantitative PCR and gel electrophoresis analysis, we investigated the changes in mitochondrial physical parameters by using flow cytometry. We also evaluated the resistance of these cells to serum starvation and sodium nitroprusside. H9c2 cells with diminished mtDNA contents showed decreased mitochondrial membrane potential, mass, free calcium, and zinc ion contents as compared to naïve H9c2 cells. Furthermore, cytosolic and mitochondrial reactive oxygen species levels were significantly higher in mtDNA-lowered H9c2 cells than in the naïve cells. Although the oxygen consumption rate and cell proliferation were decreased, mtDNA-lowered H9c2 cells were more resistant to serum deprivation and nitroprusside insults than the naïve H9c2 cells. Taken together, we conclude that the low abundance of mtDNA cause changes in cellular status, such as changes in reactive oxygen species, calcium, and zinc ion levels inducing resistance to stress. © 2015 International Federation for Cell Biology.

Sex-specific effects of cardiovascular risk factors on endothelium-dependent dilation and endothelin activity in middle-aged women and men.

PubMed

Brar, Vijaywant; Gill, Sartaj; Cardillo, Carmine; Tesauro, Manfredi; Panza, Julio A; Campia, Umberto

2015-01-01

Healthy middle-aged postmenopausal women have higher endothelium-dependent dilation and lower vasoconstrictor activity of endothelin-1 than men. Whether these sex-specific differences extend to patients with cardiovascular risk factors has not been investigated. The current study aimed to determine whether, in patients with cardiovascular risk factors, sex-specific differences exist in endothelium-dependent dilation and endothelin-1 activity. Forearm blood flow responses were measured by strain-gauge plethysmography during the intra-arterial infusion of acetylcholine, sodium nitroprusside, and the selective endothelin type A receptor blocker BQ-123 in 50 women and 64 men with cardiovascular risk factors. Acetylcholine and sodium nitroprusside induced a significant vasodilation in women and men alike (p < 0.01 for both). Also BQ-123 caused a significant vasodilation (p < 0.001) in both groups. The vasodilator response to acetylcholine was greater in women compared to men; however there were no differences in the response to sodium nitroprusside and BQ-123 (p = NS for both) between the two sex groups. Middle-aged women with cardiovascular risk factors have significantly higher endothelium-dependent dilation than middle-aged men; however, vascular endothelin 1 activity is similar in the two groups. These findings suggest that the presence of cardiovascular risk factors is associated with sex-specific effects on endothelium-dependent dilation but not on endothelin 1 activity. Further study is needed to confirm our findings and to characterize the mechanisms underlying this sex-specific regulation of endothelial function.

Copper(II) cyanido-bridged bimetallic nitroprusside-based complexes: Syntheses, X-ray structures, magnetic properties, {sup 57}Fe Moessbauer spectroscopy and thermal studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Travnicek, Zdenek, E-mail: zdenek.travnicek@upol.c; Herchel, Radovan; Mikulik, Jiri

2010-05-15

Three heterobimetallic cyanido-bridged copper(II) nitroprusside-based complexes of the compositions [Cu(tet)Fe(CN){sub 5}NO].H{sub 2}O (1), where tet=N,N'-bis(3-aminopropyl)ethylenediamine, [Cu(hto)Fe(CN){sub 5}NO].2H{sub 2}O (2), where hto=1,3,6,9,11,14-hexaazatricyclo[12.2.1.1{sup 6,9}]octadecane and [Cu(nme){sub 2}Fe(CN){sub 5}NO].H{sub 2}O (3), where nme=N-methylethylenediamine, were synthesized and characterized by elemental analyses, {sup 57}Fe Moessbauer and FTIR spectroscopies, thermal analysis, magnetic measurements and single-crystal X-ray analysis. The products of thermal degradation processes of 2 and 3 were studied by XRD, {sup 57}Fe Moessbauer spectroscopy, SEM and EDS, and they were identified as mixtures of CuFe{sub 2}O{sub 4} and CuO. - Three heterobimetallic cyano-bridged copper(II) nitroprusside-based complexes of the general compositions of [Cu(L)Fe(CN){sub 5}NO].xH{sub 2}O, wheremore » L=N,N'-bis(3-aminopropyl)ethylenediamine (complex 1), 1,3,6,9,11,14-hexaazatricyclo[12.2.1.1{sup 6,9}]-octadecane (complex 2) and N-methylethylenediamine (complex 3), were synthesized, and fully structurally and magnetically characterized. SEM, EDS, XRD and {sup 57}Fe Moessbauer experiments were used for characterization of thermal decomposition products of complexes 2 and 3.« less

Copper(II) cyanido-bridged bimetallic nitroprusside-based complexes: Syntheses, X-ray structures, magnetic properties, 57Fe Mössbauer spectroscopy and thermal studies

NASA Astrophysics Data System (ADS)

Trávníček, Zdeněk; Herchel, Radovan; Mikulík, Jiří; Zbořil, Radek

2010-05-01

Three heterobimetallic cyanido-bridged copper(II) nitroprusside-based complexes of the compositions [Cu(tet)Fe(CN) 5NO]·H 2O ( 1), where tet= N,N' -bis(3-aminopropyl)ethylenediamine, [Cu(hto)Fe(CN) 5NO]·2H 2O ( 2), where hto=1,3,6,9,11,14-hexaazatricyclo[12.2.1.1 6,9]octadecane and [Cu(nme) 2Fe(CN) 5NO]·H 2O ( 3), where nme= N-methylethylenediamine, were synthesized and characterized by elemental analyses, 57Fe Mössbauer and FTIR spectroscopies, thermal analysis, magnetic measurements and single-crystal X-ray analysis. The products of thermal degradation processes of 2 and 3 were studied by XRD, 57Fe Mössbauer spectroscopy, SEM and EDS, and they were identified as mixtures of CuFe 2O 4 and CuO.

Substance P relaxes rat bronchial smooth muscle via epithelial prostanoid synthesis.

PubMed

Bodelsson, M; Blomquist, S; Caverius, K; Törnebrandt, K

1999-01-01

Substance P is present in bronchial nerve fibres. The physiological actions of substance P are mediated via tachykinin NK(1) receptors. Immunochemical studies have demonstrated tachykinin NK(1) receptors in the rat airway epithelium. To elucidate how epithelial tachykinin NK(1) receptors affect smooth muscle response to substance P. Contractile response of isolated rat bronchial trunk with or without epithelium was recorded. In intact segments precontracted by 5-hydroxytryptamine, relaxation was induced by substance P and the nitric oxide donor, sodium nitroprusside. Removal of the epithelium abolished relaxation induced by substance P but did not affect relaxation induced by sodium nitroprusside. The cyclo-oxygenase inhibitor, indomethacin, but not the nitric oxide synthase inhibitor, L-N(G)-monomethylarginine, reduced the relaxation in response to substance P. Epithelial tachykinin NK(1) receptors mediate substance-P-induced relaxation of rat bronchial smooth muscle via release of prostanoids but not nitric oxide.

Ascorbic acid prevents vascular dysfunction induced by oral glucose load in healthy subjects.

PubMed

De Marchi, Sergio; Prior, Manlio; Rigoni, Anna; Zecchetto, Sara; Rulfo, Fanny; Arosio, Enrico

2012-01-01

To examine the effects of oral glucose load on forearm circulatory regulation before and after ascorbic acid administration in healthy subjects. Microcirculation study with laser Doppler was performed at the hand in basal conditions, after ischemia and after acetylcholine and nitroprusside; strain gauge plethysmography was performed at basal and after ischemia. The tests were repeated in the same sequence 2 hour after oral administration of glucose (75 g). The subjects were randomised for administration of ascorbic acid (1 g bid) or placebo (sodium bicarbonate 1 g bid) for 10 days. After that, the tests were repeated before and after a new oral glucose load. Blood pressure and heart rate were monitored. Macrocirculatory flux, pressure values and heart rate were unvaried throughout the study. The glucose load caused a reduction in the hyperemic peak flow with laser Doppler and plethysmography; it reduced flux recovery time and hyperemic curve area after ischemia; acetylcholine elicited a minor increase in flux with laser Doppler. The response to nitroprusside was unvaried after glucose load as compared to basal conditions. Treatment with ascorbic acid prevented the decrease in hyperemia after glucose, detected with laser Doppler and plethysmography. Ascorbic acid prevented the decreased response to acetylcholine after glucose, the response to nitroprusside was unaffected by ascorbic acid. Results after placebo were unvaried. Oral glucose load impairs endothelium dependent dilation and hyperaemia at microcirculation, probably via oxidative stress; ascorbic acid can prevent it. Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

77 FR 16039 - Abbott Laboratories et al.; Withdrawal of Approval of 35 New Drug Applications and 64 Abbreviated...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-19

... Do. nitroprusside for Injection USP), 50 mg. ANDA 071015 Haloperidol Oral Teva Pharmaceuticals... 075065 Acyclovir Sodium for Do. Injection. ANDA 075176 Haloperidol Do. Decanoate Injection, 50 mg/mL and...

Effect of infusion pump fill-stroke flow interruption on response to sodium nitroprusside in surgical patients.

PubMed

Mann, H J; Fuhs, D W; Cerra, F B

1988-03-01

The influence of the piston-cassette pump fill stroke on the pharmacodynamic response to sodium nitroprusside was evaluated prospectively in 10 adult patients in the surgical intensive-care unit. Simultaneous analog recordings of blood pressure and fill stroke were made over three complete pump fill cycles in each patient. Sodium nitroprusside flow rates and concentrations were recorded throughout the data-collection period. Analysis was based on the maximum pressure obtained during the two-minute baseline period before a fill stroke (Pmax baseline), the pressure at the initiation of the fill stroke (P initial), and the maximum pressure obtained during the two-minute period after the fill stroke (Pmax postfill). The maximum systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) during the baseline and post-fill-stroke periods were significantly different. The mean (+/- S.D.) variability in pressure between the time periods Pmax baseline and Pmax postfill was 3.9 +/- 5.8 mm Hg for SBP (range, -8 to +16), 3.5 +/- 5.7 mm Hg for DBP (range, -7 to +13), and 3.6 +/- 5.6 mm Hg for MBP (range, -7 to +14). The likelihood of a pharmacodynamic change was inconsistent both between and within patients. Within patients the difference between cycles for the variability between time periods ranged from a minimum of 2 mm Hg to a maximum of 16 mm Hg for SBP, 2 mm Hg to 17 mm Hg for DBP, and 1 mm Hg to 17 mm Hg for MBP. The variability within the baseline period (Pmax baseline - P initial) in SBP was significantly greater than the variability between the time periods, while the differences for DBP and MBP were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Haemodynamic effects of vasoactive agents following chronic state of high cardiac output in anaesthetized rats.

PubMed

Guo, Liang; Tabrizchi, Reza

2008-05-31

The arteriovenous fistula model of circulation can produce a high output and low peripheral resistance situation. Here, we have examined the effects of noradrenaline, vasopressin and sodium nitroprusside on cardiac index, mean arterial blood pressure, venous tone, resistance to venous return, arterial resistance, and blood volume in chronically shunted anaesthetized rats. The cardiac index of rats with chronic arteriovenous fistula (AVF) was significantly higher (36.65+/-2.28 ml/min per 100 g; (mean+/-S.E.M.; n=24) in comparison to sham-operated rats (20.04+/-0.86 ml/min per 100 g; mean+/-S.E.M.; n=8). Cardiac index did not significantly change during the infusion of noradrenaline (1.0, 3.0 and 10 microg/kg per min), vasopressin (10, 30, 100 ng/kg per min) or sodium nitroprusside (0.1, 0.3 and 1.0 microg/kg per min) compared to saline infusion in AVF animals. Infusion of noradrenaline significantly increased heart rate, dP/dt, mean circulatory filling pressure (Pmcf) and resistance to venous return without affecting mean arterial blood pressure when compared to saline infusion. Administration of vasopressin significantly increased dP/dt, mean arterial blood pressure, and Pmcf without affecting heart rate, resistance to venous return or arterial resistance compared to saline infusion. Infusion of sodium nitroprusside did not significantly affect any haemodynamic parameter measured when compared to saline infusion. The results indicate that the presence of chronic AVF alters responsiveness of the various segments of the circulatory system to vasoactive agents. Moreover, it produces a major impediment to overall changes that can normally be induced following the infusion of such agents.

Contractile activity of the bladder urothelium/lamina propria and its regulation by nitric oxide.

PubMed

Moro, Christian; Leeds, Charlotte; Chess-Williams, Russ

2012-01-15

In the bladder, nitric oxide (NO) is released from neuronal and non-neuronal sources, but its actions are unclear. Strips of urothelium plus lamina propria contract in response to agonists and develop spontaneous phasic contractions, and the aim of this study was to investigate the influence of NO on this activity. Isolated strips of urothelium/lamina propria from porcine bladder developed spontaneous contractions (3.5 ± 0.3 cycles/min) and contracted in response to carbachol and electrical field stimulation (EFS). The NO synthase inhibitor N(ω)-nitro-l-arginine (L-NNA, 100 μM) had no effects on the tissues, but the NO donors diethylamine NONOate (DEANO, 100 μM) and nitroprusside (10 μM) caused relaxation, slowed the spontaneous rate of contractions and inhibited responses to carbachol. Maximum tonic contractions to carbachol were reduced by 17 ± 4% (P<0.001) and 35 ± 5% (P<0.001) by DEANO and nitroprusside respectively and the potency of carbachol was also reduced. Carbachol also increased the spontaneous frequency of contraction and these rate responses were again inhibited by DEANO and nitroprusside, but unaffected by L-NNA. Similarly, responses to EFS were significantly depressed (52-70%) by DEANO (P<0.05), but were unaffected by L-NNA. These data demonstrate spontaneous contractile activity and also nerve and agonist-induced tonic contractile activity within the urothelium and lamina propria. This activity is sensitive to depression by NO, but NO does not appear to be spontaneously released to influence this activity, nor does it appear to be released by muscarinic receptor stimulation. However the results suggest that in situations where NO production is increased, NO can influence the contractile activity of this tissue. Copyright © 2011 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gil, D.M.; Osiry, H.; Pomiro, F.

The hydrogen bond and π-π stacking are two non-covalent interactions able to support cooperative magnetic ordering between paramagnetic centers. This contribution reports the crystal structure and related magnetic properties for VO[Fe(CN){sub 5}NO]·2H{sub 2}O, which has a layered structure. This solid crystallizes with an orthorhombic unit cell, in the Pna2{sub 1} space group, with cell parameters a=14.1804(2), b=10.4935(1), c=7.1722(8) Å and four molecules per unit cell (Z=4). Its crystal structure was solved and refined from powder X-ray diffraction data. Neighboring layers remain linked through a network of hydrogen bonds involving a water molecule coordinated to the axial position for the Vmore » atom and the unbridged axial NO and CN ligands. An uncoordinated water molecule is found forming a triple bridge between these last two ligands and the coordinated water molecule. The magnetic measurements, recorded down to 2 K, shows a ferromagnetic interaction between V atoms located at neighboring layers, with a Curie-Weiss constant of 3.14 K. Such ferromagnetic behavior was interpreted as resulting from a superexchange interaction through the network of strong OH····O{sub H2O}, OH····N{sub CN}, and OH····O{sub NO} hydrogen bonds that connects neighboring layers. The interaction within the layer must be of antiferromagnetic nature and it was detected close to 2 K. - Graphical abstract: Coordination environment for the metals in vanadyl (II) nitroprusside dihydrate. Display Omitted - Highlights: • Crystal structure of vanadyl nitroprusside dehydrate. • Network of hydrogen bonds. • Magnetic interactions through a network of hydrogen bonds. • Layered transition metal nitroprussides.« less

Vascular smooth muscle relaxation mediated by nitric oxide donors: a comparison with acetylcholine, nitric oxide andnitroxyl ion

PubMed Central

Wanstall, Janet C; Jeffery, Trina K; Gambino, Agatha; Lovren, Fina; Triggle, Christopher R

2001-01-01

Vasorelaxant properties of three nitric oxide (NO) donor drugs (glyceryl trinitrate, sodium nitroprusside and spermine NONOate) in mouse aorta (phenylephrine pre-contracted) were compared with those of endothelium-derived NO (generated with acetylcholine), NO free radical (NO·; NO gas solution) and nitroxyl ion (NO−; from Angeli's salt). The soluble guanylate cyclase inhibitor, ODQ (1H-(1,2,4-)oxadiazolo(4,3-a)-quinoxalin-1-one; 0.3, 1 and 10 μM), concentration-dependently inhibited responses to all agents. 10 μM ODQ abolished responses to acetylcholine and glyceryl trinitrate, almost abolished responses to sodium nitroprusside but produced parallel shifts (to a higher concentration range; no depression in maxima) in the concentration-response curves for NO gas solution, Angeli's salt and spermine NONOate. The NO· scavengers, carboxy-PTIO, (2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide; 100 μM) and hydroxocobalamin (100 μM), both inhibited responses to NO gas solution and to the three NO donor drugs, but not Angeli's salt. Hydroxocobalamin, but not carboxy-PTIO, also inhibited responses to acetylcholine. The NO− inhibitor, L-cysteine (3 mM), inhibited responses to Angeli's salt, acetylcholine and the three NO donor drugs, but not NO gas solution. The data suggest that, in mouse aorta, responses to all three NO donors involve (i) activation of soluble guanylate cyclase, but to differing degrees and (ii) generation of both NO· and NO−. Glyceryl trinitrate and sodium nitroprusside, which generate NO following tissue bioactivation, have profiles resembling the profile of endothelium-derived NO more than that of exogenous NO. Spermine NONOate, which generates NO spontaneously outside the tissue, was the drug that most closely resembled (but was not identical to) exogenous NO. PMID:11588100

Evidence for metaboreceptor stimulation of sweating in normothermic and heat-stressed humans

NASA Technical Reports Server (NTRS)

Shibasaki, M.; Kondo, N.; Crandall, C. G.

2001-01-01

1. Isometric handgrip (IHG) exercise increases sweat rate and arterial blood pressure, and both remain elevated during post-exercise ischaemia. The purpose of this study was to identify whether the elevation in arterial blood pressure during post-exercise ischaemia contributes to the increase in sweating. 2. In normothermia and during whole-body heating, 2 min IHG exercise at 40% maximal voluntary contraction, followed by 2 min post-exercise ischaemia, was performed with and without bolus intravenous administration of sodium nitroprusside during the ischaemic period. Sodium nitroprusside was administered to reduce blood pressure during post-exercise ischaemia to pre-exercise levels. Sweat rate was monitored over two microdialysis membranes placed in the dermal space of forearm skin. One membrane was perfused with the acetylcholinesterase inhibitor neostigmine, while the other was perfused with the vehicle. 3. In normothermia, IHG exercise increased sweat rate at the neostigmine-treated site but not at the control site. Sweat rate remained elevated during post-exercise ischaemia even after mean arterial blood pressure returned to the pre-IHG exercise baseline. Subsequent removal of the ischaemia stimulus returned sweat rate to pre-IHG exercise levels. Sweat rate during post-exercise ischaemia without sodium nitroprusside administration followed a similar pattern. 4. During whole-body heating, IHG exercise increased sweat rate at both neostigmine-treated and untreated sites. Similarly, regardless of whether mean arterial blood pressure remained elevated or was reduced during post-exercise ischaemia, sweat rate remained elevated during the ischaemic period. 5. These results suggest that sweating in non-glabrous skin during post-IHG exercise ischaemia is activated by metaboreflex stimulation and not via baroreceptor loading.

Absence of arterial baroreflex modulation of skin sympathetic activity and sweat rate during whole-body heating in humans

NASA Technical Reports Server (NTRS)

Wilson, T. E.; Cui, J.; Crandall, C. G.

2001-01-01

1. Prior findings suggest that baroreflexes are capable of modulating skin blood flow, but the effects of baroreceptor loading/unloading on sweating are less clear. Therefore, this project tested the hypothesis that pharmacologically induced alterations in arterial blood pressure in heated humans would lead to baroreflex-mediated changes in both skin sympathetic nerve activity (SSNA) and sweat rate. 2. In seven subjects mean arterial blood pressure was lowered (approximately 8 mmHg) and then raised (approximately 13 mmHg) by bolus injections of sodium nitroprusside and phenylephrine, respectively. Moreover, in a separate protocol, arterial blood pressure was reduced via steady-state administration of sodium nitroprusside. In both normothermia and heat-stress conditions the following responses were monitored: sublingual and mean skin temperatures, heart rate, beat-by-beat blood pressure, skin blood flow (laser-Doppler flowmetry), local sweat rate and SSNA (microneurography from peroneal nerve). 3. Whole-body heating increased skin and sublingual temperatures, heart rate, cutaneous blood flow, sweat rate and SSNA, but did not change arterial blood pressure. Heart rate was significantly elevated (from 74 +/- 3 to 92 +/- 4 beats x min(-1); P < 0.001) during bolus sodium nitroprusside-induced reductions in blood pressure, and significantly reduced (from 92 +/- 4 to 68 +/- 4 beats x min(-1); P < 0.001) during bolus phenylephrine-induced elevations in blood pressure, thereby demonstrating normal baroreflex function in these subjects. 4. Neither SSNA nor sweat rate was altered by rapid (bolus infusion) or sustained (steady-state infusion) changes in blood pressure regardless of the thermal condition. 5. These data suggest that SSNA and sweat rate are not modulated by arterial baroreflexes in normothermic or moderately heated individuals.

Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation

PubMed Central

Mills, Nicholas L.; Miller, Mark R.; Lucking, Andrew J.; Beveridge, Jon; Flint, Laura; Boere, A. John F.; Fokkens, Paul H.; Boon, Nicholas A.; Sandstrom, Thomas; Blomberg, Anders; Duffin, Rodger; Donaldson, Ken; Hadoke, Patrick W.F.; Cassee, Flemming R.; Newby, David E.

2011-01-01

Aim Exposure to road traffic and air pollution may be a trigger of acute myocardial infarction, but the individual pollutants responsible for this effect have not been established. We assess the role of combustion-derived-nanoparticles in mediating the adverse cardiovascular effects of air pollution. Methods and results To determine the in vivo effects of inhalation of diesel exhaust components, 16 healthy volunteers were exposed to (i) dilute diesel exhaust, (ii) pure carbon nanoparticulate, (iii) filtered diesel exhaust, or (iv) filtered air, in a randomized double blind cross-over study. Following each exposure, forearm blood flow was measured during intra-brachial bradykinin, acetylcholine, sodium nitroprusside, and verapamil infusions. Compared with filtered air, inhalation of diesel exhaust increased systolic blood pressure (145 ± 4 vs. 133 ± 3 mmHg, P< 0.05) and attenuated vasodilatation to bradykinin (P= 0.005), acetylcholine (P= 0.008), and sodium nitroprusside (P< 0.001). Exposure to pure carbon nanoparticulate or filtered exhaust had no effect on endothelium-dependent or -independent vasodilatation. To determine the direct vascular effects of nanoparticulate, isolated rat aortic rings (n= 6–9 per group) were assessed in vitro by wire myography and exposed to diesel exhaust particulate, pure carbon nanoparticulate and vehicle. Compared with vehicle, diesel exhaust particulate (but not pure carbon nanoparticulate) attenuated both acetylcholine (P< 0.001) and sodium-nitroprusside (P= 0.019)-induced vasorelaxation. These effects were partially attributable to both soluble and insoluble components of the particulate. Conclusion Combustion-derived nanoparticulate appears to predominately mediate the adverse vascular effects of diesel exhaust inhalation. This provides a rationale for testing environmental health interventions targeted at reducing traffic-derived particulate emissions. PMID:21753226

Load dependence of the effective regurgitant orifice area in a sheep model of aortic regurgitation.

PubMed

Reimold, S C; Byrne, J G; Caguioa, E S; Lee, C C; Laurence, R G; Peigh, P S; Cohn, L H; Lee, R T

1991-10-01

Treatment of patients with aortic regurgitation with vasodilators reduces regurgitant volume, ventricular dilation and left ventricular mass. Although these effects are presumably due to afterload reduction, it is also possible that the aortic regurgitant orifice area is not constant. To test the latter hypothesis, aortic regurgitation was created in 10 open chest sheep by partial resection of the noncoronary leaflet under direct visualization. Regurgitant flow was measured with an aortic supravalvular electromagnetic probe; aortic and left ventricular pressures were measured with catheter-tipped micromanometer pressure transducers. The effective regurgitant orifice area was calculated by a modification of the continuity equation in a manner similar to the Gorlin equation. The regurgitant orifice area was measured three times: after aortic regurgitation was created, after mean arterial pressure was increased by 15 to 25 mm Hg with intravenous dopamine and after mean arterial pressure was reduced by 15 to 25 mm Hg with intravenous sodium nitroprusside. Comparison of regurgitant volumes and areas obtained after creation of aortic regurgitation and at the conclusion of the experiment in the absence of dopamine or sodium nitroprusside demonstrated no significant change over time. Dopamine administration was associated with an 86 +/- 81% increase in regurgitant volume (p less than 0.01) and a 38 +/- 44% increase in regurgitant orifice area (p less than 0.01). Sodium nitroprusside administration resulted in a 51 +/- 14% decrease in regurgitant volume (p less than 0.001) and a 28 +/- 21% reduction in regurgitant orifice area (p = 0.007). In this model of acute aortic regurgitation, the effective regurgitant orifice area was altered by increasing or decreasing the aortic transvalvular pressure gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitroprusside inhibits calcium-induced impairment of red blood cell deformability.

PubMed

Barodka, Viachaslau; Mohanty, Joy G; Mustafa, Asif K; Santhanam, Lakshmi; Nyhan, Aoibhinn; Bhunia, Anil K; Sikka, Gautam; Nyhan, Daniel; Berkowitz, Dan E; Rifkind, Joseph M

2014-02-01

Red blood cell (RBC) deformation is critical for microvascular perfusion and oxygen delivery to tissues. Abnormalities in RBC deformability have been observed in aging, sickle cell disease, diabetes, and preeclampsia. Although nitric oxide (NO) prevents decreases in RBC deformability, the underlying mechanism is unknown. As an experimental model, we used ionophore A23187-mediated calcium influx in RBCs to reduce their deformability and investigated the role of NO donor sodium nitroprusside (SNP) and KCa3.1 (Gardos) channel blockers on RBC deformability (measured as elongation index [EI] by microfluidic ektacytometry). RBC intracellular Ca(2+) and extracellular K(+) were measured by inductively coupled plasma mass spectrometry and potassium ion selective electrode, respectively. SNP treatment of RBCs blocked the Ca(2+) (approx. 10 μmol/L)-induced decrease in RBC deformability (EI 0.34 ± 0.02 vs. 0.09 ± 0.01, control vs. Ca(2+) loaded, p < 0.001; and EI 0.37 ± 0.02 vs. 0.30 ± 0.01, SNP vs. SNP plus Ca(2+) loaded) as well as Ca(2+) influx and K(+) efflux. The SNP effect was similar to that observed after pharmacologic blockade of the KCa3.1 channel (with charybdotoxin or extracellular medium containing isotonic K(+) concentration). In RBCs from KCa3.1(-/-) mice, 10 μmol/L Ca(2+) loading did not decrease cellular deformability. A preliminary attempt to address the molecular mechanism of SNP protection suggests the involvement of cell surface thiols. Our results suggest that nitroprusside treatment of RBCs may protect them from intracellular calcium increase-mediated stiffness, which may occur during microvascular perfusion in diseased states, as well as during RBC storage. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Evaluation of the Zeiss retinal vessel analyser

PubMed Central

Polak, K.; Dorner, G.; Kiss, B.; Polska, E.; Findl, O.; Rainer, G.; Eichler, H.; Schmetterer, L.

2000-01-01

AIM—To investigate the reproducibility and sensitivity of the Zeiss retinal vessel analyser, a new method for the online determination of retinal vessel diameters in healthy subjects.
METHODS—Two model drugs were administered, a peripheral vasoconstrictor (the α receptor agonist phenylephrine) and a peripheral vasodilator (the nitric oxide donor sodium nitroprusside) in stepwise increasing doses. Nine healthy young subjects were studied in a placebo controlled double masked three way crossover design. Subjects received intravenous infusions of either placebo or stepwise increasing doses of phenylephrine (0.5, 1, or 2 µg/kg/min) or sodium nitroprusside (0.5, 1, or 2 µg/kg/min). Retinal vessel diameters were measured with the new Zeiss retinal vessel analyser. Retinal leucocyte velocity, flow, and density were measured with the blue field entoptic technique. The reproducibility of measurements was assessed with coefficients of variation and intraclass correlation coefficients.
RESULTS—Placebo and phenylephrine did not influence retinal haemodynamics, although the α receptor antagonist significantly increased blood pressure. Sodium nitroprusside induced a significant increase in retinal venous and arterial diameters (p<0.001 each), leucocyte density (p=0.001), and leucocyte flow (p=0.024) despite lowering blood pressure to a significant degree. For venous and arterial vessel size measurements short term coefficients of variation were 1.3% and 2.6% and intraclass correlation coefficients were 0.98 and 0.96, respectively. The sensitivity was between 3% and 5% for retinal veins and 5% and 7% for retinal arteries.
CONCLUSIONS—These data indicate that the Zeiss retinal vessel analyser is an accurate system for the assessment of retinal diameters in healthy subjects. In addition, nitric oxide appears to have a strong influence on retinal vascular tone.

 PMID:11049956

Comparison of Hydrogen Sulfide Analysis Techniques

ERIC Educational Resources Information Center

Bethea, Robert M.

1973-01-01

A summary and critique of common methods of hydrogen sulfide analysis is presented. Procedures described are: reflectance from silver plates and lead acetate-coated tiles, lead acetate and mercuric chloride paper tapes, sodium nitroprusside and methylene blue wet chemical methods, infrared spectrophotometry, and gas chromatography. (BL)

EFFECT OF AT1 RECEPTOR BLOCKADE ON INTERMITTENT HYPOXIA-INDUCED ENDOTHELIAL DYSFUNCTION

PubMed Central

Marcus, Noah J.; Philippi, Nathan R.; Bird, Cynthia E.; Li, Yu-Long; Schultz, Harold D.; Morgan, Barbara J.

2012-01-01

Chronic intermittent hypoxia (CIH) raises arterial pressure, impairs vasodilator responsiveness, and increases circulating angiotensin II (Ang II); however, the role of Ang II in CIH-induced vascular dysfunction is unknown. Rats were exposed to CIH or room air (NORM), and a subset of these animals was treated with losartan (Los) during the exposure period. After 28 days, vasodilatory responses to acetylcholine or nitroprusside were measured in isolated gracilis arteries. Superoxide levels and Ang II receptor protein expression were measured in saphenous arteries. After 28 days, arterial pressure was increased and acetylcholine-induced vasodilation was blunted in CIH vs. NORM, and this was prevented by Los. Responses to nitroprusside and superoxide levels did not differ between CIH and NORM. Expression of AT2R was decreased and the AT1R:AT2R ratio was increased in CIH vs. NORM, but this was unaffected by Los. These results indicate that the blood pressure elevation and endothelial dysfunction associated with CIH is dependent, at least in part, on RAS signaling. PMID:22728949

Neuroprotective effects of curcumin and highly bioavailable curcumin on oxidative stress induced by sodium nitroprusside in rat striatal cell culture.

PubMed

Nazari, Qand Agha; Kume, Toshiaki; Izuo, Naotaka; Takada-Takatori, Yuki; Imaizumi, Atsushi; Hashimoto, Tadashi; Izumi, Yasuhiko; Akaike, Akinori

2013-01-01

Curcumin, a polyphenolic compound extracted from Curcuma longa, has several pharmacological activities such as anticancer, anti-inflammatory, and antioxidant effects. The purpose of this study was to investigate the protective effects of curcumin and THERACURMIN, a highly bioavailable curcumin, against sodium nitroprusside (SNP)-induced oxidative damage in primary striatal cell culture. THERACURMIN as well as curcumin significantly prevented SNP-induced cytotoxicity. To elucidate the cytoprotective effects of curcumin and THERACURMIN, we measured the intracellular glutathione level in striatal cells. Curcumin and THERACURMIN significantly elevated the glutathione level, which was decreased by treatment with SNP. Moreover, curcumin showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging ability. Finally, a ferrozine assay showed that curcumin (10-100 µg/mL) has potent Fe(2+)-chelating ability. These results suggest that curcumin and THERACURMIN exert potent protective effects against SNP-induced cytotoxicity by free radical-scavenging and iron-chelating activities.

BP and Vascular Function Following Space Flight

NASA Technical Reports Server (NTRS)

Hatton, Daniel C.; Yue, Qi; Chapman, Justin; Xue, Hong; Dierickx, Jacqueline; Roullet, Chantal; Roullet, Jean-Baptiste; Phanouvong, Thongchanh; Watanabe, Mitsuaki; Otsuka, Keiichi;

List of Error-Prone Abbreviations, Symbols, and Dose Designations

MedlinePlus

... unit dose (e.g., diltiazem 125 mg IV infusion “UD” misin- terpreted as meaning to give the entire infusion as a unit [bolus] dose) Use “as directed” ... Names Intended Meaning Misinterpretation Correction “Nitro” drip nitroglycerin infusion Mistaken as sodium nitroprusside infusion Use complete drug ...

Response to reactive nitrogen intermediates in Mycobacterium tuberculosis: induction of the 16-kilodalton alpha-crystallin homolog by exposure to nitric oxide donors.

PubMed

Garbe, T R; Hibler, N S; Deretic, V

1999-01-01

In contrast to the apparent paucity of Mycobacterium tuberculosis response to reactive oxygen intermediates, this organism has evolved a specific response to nitric oxide challenge. Exposure of M. tuberculosis to NO donors induces the synthesis of a set of polypeptides that have been collectively termed Nox. In this work, the most prominent Nox polypeptide, Nox16, was identified by immunoblotting and by N-terminal sequencing as the alpha-crystallin-related, 16-kDa small heat shock protein, sHsp16. A panel of chemically diverse donors of nitric oxide, with the exception of nitroprusside, induced sHsp16 (Nox16). Nitroprusside, a coordination complex of Fe2+ with a nitrosonium (NO+) ion, induced a 19-kDa polypeptide (Nox19) homologous to the nonheme bacterial ferritins. We conclude that the NO response in M. tuberculosis is dominated by increased synthesis of the alpha-crystallin homolog sHsp16, previously implicated in stationary-phase processes and found in this study to be a major M. tuberculosis protein induced upon exposure to reactive nitrogen intermediates.

Formation of peroxynitrite during thiol-mediated reduction of sodium nitroprusside.

PubMed

Aleryani, S; Milo, E; Kostka, P

1999-10-18

Aerobic incubations of equimolar concentrations (5-500 microM) of sodium nitroprusside (SNP) and dithiothreitol (DTT) carried out at pH 7.4 in the absence of light caused a concentration-dependent increase in the rates of oxidation of dihydrorhodamine-123. The enhancement of the rates of oxidation under such conditions was only partially sensitive to the inhibition by 100 mM dimethyl sulfoxide implying the involvement of both peroxynitrite and hydroxyl radicals in the observed effects. The oxidation of dihydrorhodamine-123 in the presence of SNP and DTT was nearly completely abolished by superoxide dismutase (20 U/ml). It was found that such an effect of the enzyme was related primarily to the stabilization of an intermediate of SNP reduction formed upstream to the liberation of nitrosonium ligand. Increased rates of oxidation of dihydrorhodamine-123 were also observed during the reduction of SNP with either L-cysteine or glutathione. It is concluded that thiol-mediated reduction of SNP under aerobic conditions is accompanied by the formation of oxygen-derived free radicals. Nitrosonium ligand liberated from the product(s) of SNP reduction is, under such conditions, converted to peroxynitrite.

Evidence for a possible role for nitric oxide in the modulation of heart activity in Achatina fulica and Helix aspersa.

PubMed

White, A R; Curtis, S A; Walker, R J

2004-02-01

The effects of nitric oxide (NO) donors, S-nitroso-N-acetylpenicillamine, S-nitroso-l-glutathione, sodium nitroprusside and sodium nitrite were investigated on the activity of the isolated hearts of Achatina fulica and Helix aspersa. NO donors inhibited heart activity in a concentration-dependent manner. The only exception was sodium nitroprusside, which excited H. aspersa heart. The inhibitory effects of these NO donors were reduced by the NO scavenger, methylene blue, the guanylyl cyclase inhibitor, 1H-(1,2,4) Oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), and potentiated by 8-Br-cGMP and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Acetylcholine also inhibited the heart activity, and this inhibition was reduced by methylene blue and ODQ. Positive NADPH-diaphorase staining was located in the outer pericardial layer of the heart of A. fulica. The present results provide evidence that NO may modulate the activity of gastropod hearts, and this modulation may modify the inhibitory action of acetylcholine on heart activity.

Effect of medication on microvascular vasodilatation in patients with systemic lupus erythematosus.

PubMed

Bengtsson, Christine; Andersson, Sven E; Edvinsson, Lars; Edvinsson, Marie-Louise; Sturfelt, Gunnar; Nived, Ola

2010-12-01

The aim of this study was to investigate the microvascular responses in the skin, to local heat, iontophoretically administered acetylcholine and to sodium nitroprusside in relation to cardiovascular damage in patients with systemic lupus erythematosus (SLE) and matched controls. We also wanted to examine if the ongoing medication in SLE patients influenced this vascular response. We investigated 30 women with SLE and compared them with 20 age and sex-matched controls. The cutaneous blood flow response to local heat (+44°C), iontophoretically administered endothelium-dependent (acetylcholine), as well as independent (sodium nitroprusside) vasodilatation, was measured by laser Doppler flowmetry. Clinical data and medication were retrieved from the clinical database and patient records. The cutaneous microvascular reactivity did not differ between SLE patients and a group of matched controls nor did it correlate with cardiovascular damage [assessed by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI)]. However, patients on antimalarial drugs (hydroxychloroquine n = 8 and chloroquine diphosphate n = 3) responded more strongly to sodium nitroprusside (endothelium-independent vasodilatation) compared with those without antimalarial drugs (p < 0.01). The response to acetylcholine was higher among patients on warfarin compared with those without (p < 0.05), whereas glucocorticoid use (≥5 mg daily) was associated with reduced response to acetylcholine (p < 0.05). Smokers in general tended to have a lower response to acetylcholine (p = 0.064). Smoking SLE patients versus non-smoking SLE patients had a significantly lower response to acetylcholine (p = 0.01). Medication with antimalarial drugs-enhanced endothelium-independent vasodilatation, while glucocorticoid use was associated with reduction and warfarin-treatment with enhancement of endothelium-dependent vasodilatation. Therefore, despite there is no difference in microvascular endothelium-dependent vasodilatation, other factors such as medication and smoking may affect vasodilatation in SLE patients. © 2010 The Authors. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic Pharmacological Society.

Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside induced lipid peroxidation in rats' pancreas by phenolic extracts of avocado pear leaves and fruit.

PubMed

Oboh, Ganiyu; Isaac, Adelusi Temitope; Akinyemi, Ayodele Jacobson; Ajani, Richard Akinlolu

2014-09-01

Persea americana fruit and leaves had been known in folk medicine for their anti-diabetic prowess. Therefore, this study sought to investigate the inhibitory effect of phenolic extract from avocado pear (Persea americana) leaves and fruits on some key enzymes linked to type 2 diabetes (α-amylase and α-glucosidase); and sodium nitroprusside (SNP) induced lipid peroxidation in rats' pancreas in vitro. The phenolic extracts of Persea americana fruit and leaves were extracted using methanol and 1M HCl (1:1 v/v). Thereafter, their inhibitory effects on sodium nitroprusside induced lipid peroxidation and key enzymes linked to type 2 diabetes (α-amylase and α-glucosidase) were determined in vitro. The result revealed that the leaves had fruit of avocado pear inhibit both α-amylase and α-glucosidase activities in a dose dependent manner. However, the Peel had the highest α-amylase inhibitory activity while the leaf had the highest α-glucosidase inhibitory activity as revealed by their IC50 value. Furthermore, incubation of the rat pancreas in the presence of 5 mM SNP caused an increase in the malondialdehyde (MDA) content in the tissue, however, introduction of the phenolic extracts inhibited MDA produced in a dose dependent manner. The additive and/or synergistic action of major phenolic compounds such as syringic acid, eugenol, vnillic acid, isoeugenol, guaiacol, kaemferol, catechin, ρ-hydroxybenzoic acid, ferulic acid, apigenin, naringenin, epigallocatechin, epicatechin, lupeol and epigallocatechin-3-O-gallate in avocado pear using gas chromatography (GC) could have contributed to the observed medicinal properties of the plant. Therefore, inhibition of some key enzymes linked to type 2 diabetes and prevention of oxidative stress in the pancreas could be some of the possible mechanism by which they exert their anti-diabetic properties.

Inhibition of Key Enzymes Linked to Type 2 Diabetes and Sodium Nitroprusside Induced Lipid Peroxidation in Rats’ Pancreas by Phenolic Extracts of Avocado Pear Leaves and Fruit

PubMed Central

Oboh, Ganiyu; Isaac, Adelusi Temitope; Akinyemi, Ayodele Jacobson; Ajani, Richard Akinlolu

2014-01-01

Persea americana fruit and leaves had been known in folk medicine for their anti-diabetic prowess. Therefore, this study sought to investigate the inhibitory effect of phenolic extract from avocado pear (Persea americana) leaves and fruits on some key enzymes linked to type 2 diabetes (α-amylase and α-glucosidase); and sodium nitroprusside (SNP) induced lipid peroxidation in rats’ pancreas in vitro. The phenolic extracts of Persea americana fruit and leaves were extracted using methanol and 1M HCl (1:1 v/v). Thereafter, their inhibitory effects on sodium nitroprusside induced lipid peroxidation and key enzymes linked to type 2 diabetes (α-amylase and α-glucosidase) were determined in vitro. The result revealed that the leaves had fruit of avocado pear inhibit both α-amylase and α-glucosidase activities in a dose dependent manner. However, the Peel had the highest α-amylase inhibitory activity while the leaf had the highest α-glucosidase inhibitory activity as revealed by their IC50 value. Furthermore, incubation of the rat pancreas in the presence of 5 mM SNP caused an increase in the malondialdehyde (MDA) content in the tissue, however, introduction of the phenolic extracts inhibited MDA produced in a dose dependent manner. The additive and/or synergistic action of major phenolic compounds such as syringic acid, eugenol, vnillic acid, isoeugenol, guaiacol, kaemferol, catechin, ρ-hydroxybenzoic acid, ferulic acid, apigenin, naringenin, epigallocatechin, epicatechin, lupeol and epigallocatechin-3-O-gallate in avocado pear using gas chromatography (GC) could have contributed to the observed medicinal properties of the plant. Therefore, inhibition of some key enzymes linked to type 2 diabetes and prevention of oxidative stress in the pancreas could be some of the possible mechanism by which they exert their anti-diabetic properties PMID:25324703

Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

PubMed

Grassi, S; Pettorossi, V E

2000-01-01

In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a sufficient level for triggering potentiation. Once the synaptic efficacy has changed, it becomes a long-lasting phenomenon only through a subsequent action of platelet-activating factor.

Uncoupling of the baroreflex by N(N)-cholinergic blockade in dissecting the components of cardiovascular regulation

NASA Technical Reports Server (NTRS)

Shannon, J. R.; Jordan, J.; Black, B. K.; Costa, F.; Robertson, D.

1998-01-01

Systemic administration of adrenergic agonists and nitric oxide donors is used extensively to determine cardiovascular receptor sensitivity. Conclusions regarding receptor sensitivity in the presence of the baroreflex may be misleading. In 8 normal volunteers, we determined the heart rate and blood pressure changes after incremental bolus doses of isoproterenol, phenylephrine, and sodium nitroprusside before and during neuronal nicotinic cholinergic (N(N)-cholinergic) blockade with trimethaphan. Results are given as median (25th/75th percentile). With trimethaphan, the baroreflex slope (as determined by bolus doses of nitroprusside and phenylephrine) decreased from 24 (22/26) to 0.00 (0.00/0.09) ms/mm Hg (P<0.01). The dose of isoproterenol that decreased systolic blood pressure (SBP) 12.5 mm Hg changed from 0.61 (0.51/5.3) to 0.17 (0.12/0.21) microg (P<0.01); the dose required to increase heart rate 12.5 bpm changed from 0.22 (0.17/0.41) to 0.74 (0.33/2.3) microg (P<0.01). The dose of nitroprusside required to decrease SBP 12.5 mm Hg changed from 2.3 (1.3/3.4) to 0.18 (0.14/0.24) microg/kg (P<0.01). The dose of phenylephrine required to increase SBP 12.5 mm Hg changed from 135 (110/200) to 16 (10/30) microg (P<0.01). We conclude that the efferent arc of the baroreflex can be completely interrupted with N(N)-cholinergic blockade. Estimation of adrenoreceptor sensitivity and sensitivity to nitric oxide donors by systemic administration of agonists is severely confounded by baroreflexes. Uncoupling of the baroreflex by N(N)-cholinergic blockade may be a useful method to obtain an integrated measure of adrenergic receptor sensitivity and sensitivity to nitric oxide donors in humans. This approach would permit the comparison of normal and abnormal physiological states without the "noise" of baroreflex buffering.

Aerosolized PGE1, PGI2 and nitroprusside protect against vascular leakage in lung ischaemia-reperfusion.

PubMed

Schütte, H; Löckinger, A; Seeger, W; Grimminger, F

2001-07-01

High permeability oedema is an important feature in lung injury secondary to ischaemia-reperfusion. This study investigated the influence of aerosolized prostaglandin E1 (PGE1), prostaglandin I2 (PCI2) and the nitric oxide (NO)-donor, sodium nitroprusside (SNP) on microvascular barrier function in pulmonary ischaemia-reperfusion. Buffer-perfused rabbit lungs were exposed to 180 or 210 min of warm ischaemia while maintaining anoxic ventilation and a positive intravascular pressure. Reperfusion provoked a transient, mostly precapillary elevation of vascular resistance, followed by a severe increase of the capillary filtration coefficient (Kfc) versus nonischaemic controls (3.17+/-0.34 versus 0.85+/-0.05 cm3 x s(-1) cmH2O(-1) x g(-1) x 10(-4) after 30 min of reperfusion), and progressive oedema formation. Short-term aerosolization of SNP, PGE1 or PGI2 at the beginning of ischaemia largely suppressed the Kfc increase (1.36+/-0.22, 1.32+/-0.23 and 1.32+/-0.22 cm3 x s(-1) x cmH2O(-1) x g(-1) x 10(-4), respectively) and oedema formation. In contrast, application prior to reperfusion was much less effective, with some reduction of Kfc increase by PGI2 and SNP and no effect of PGE, (1.79+/-0.31, 2.2+/-0.53 and 3.2+/-0.05 cm3 x s(-1) x cmH2O(-1) x g(-1) x 10(-4), respectively). Haemodynamics, including microvascular pressure, were only marginally affected by the chosen doses of aerosolized vasodilators. It is concluded that short-term aerosolization of prostaglandin E1, prostaglandin I2 and sodium nitroprusside at the onset of ischaemia is highly effective in maintaining endothelial barrier properties in pulmonary ischaemia-reperfusion. This effect is apparently attributable to nonvasodilatory mechanisms exerted by these agents. Alveolar deposition of prostaglandins and/or nitric oxide donors by the aerosol technique may offer pulmonary protection in ischaemia-reperfusion injury.

Treatment with sodium nitroprusside improves the endothelial function in aortic rings with endothelial dysfunction.

PubMed

Buzinari, Tereza Cristina; Oishi, Jorge Camargo; De Moraes, Thiago Francisco; Vatanabe, Izabela Pereira; Selistre-de-Araújo, Heloisa Sobreiro; Pestana, Cezar Rangel; Rodrigues, Gerson Jhonatan

2017-07-15

Verify if sodium nitroprusside (SNP) is able to improve endothelial function and if this effect is independent of nitric oxide (NO) release of the compound. Normotensive (2K) and hypertensive (2K-1C) wistar rats were used. Intact endothelium aortas were placed in a myograph and incubated with SNP: 0.1nM; 1nM or 10nM during 30min. Cumulative concentration-effect curves for acetylcholine (Ach) were realized to measure the relaxing capacity. Intracellular NO were measured (by DAF-2DA probe) in HUVEC treated with SNP 0.1nM or DETA/NO 0.1μM. The detection of intracellular superoxide radical (O 2 •- ) was obtained by using DHE probe. Treatment of 2K-1C aortic rings with SNP (0.1; 1.0 and 10nM) improved endothelium dependent relaxation induced by acetylcholine. This improvement induced by SNP was verified at the concentration of 0.1nM, which does not release NO, suggesting that this effect was not induced due to NO release by SNP compound. Besides, we show that the cell treatment with 0.1nM of SNP decreased the fluorescence intensity to DHE in cells stimulated with angiotensin II. These results indicate that SNP decreases the concentration of O 2 •- in HUVEC cells. The SNP at a concentration that does not release NO inside the cells is able to attenuate endothelial dysfunction. Acetylcholine (Ach) (PubChem CID:6060); angiotensin II human (Ang II) (PubChem CID: 16211177); diethylenetriamine/nitric oxide (DETA-NO) (PubChem CID 4518); dihydroethidium (DHE) (PubChem CID: 128682); phenylephrine (Phe) (PubChem CID: 5284443); sodium nitroprusside (SNP) (PubChem CID: 11963579); Thiazolyl Blue Tetrazolium Bromide (MTT) (PubChem CID: 64965); 4,5-diaminofluorescein diacetate (DAF-2DA); 4-hidroxy-Tempo (Tempol) (PubChem CID: 137994), were purchased from Sigma-Aldrich (St. Louis, MO, USA). Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical Investigation Program. Annual Progress Report

DTIC Science & Technology

1990-10-01

1990 (C) Stevens EL, Venkataraman BW, Southgate M, Nakamura KT: Ontogeny of Sodium Nitroprusside and Atriopeptin III Relaxation in Guinea Pig Airway...of Nephrology Conference, Dec 89 Malinowski TR: Rhabdomyolysis Following Vaccination for Influenza. Hawaii Chapter Scientific Meeting, American College...Muscle Response to Acetylcholine and Histamine. Society for Pediatric Research Meeting, Anaheim, CA, May 90 (C) Stevens EL, Venkataraman BW, Southgate M

Endothelium-derived relaxing factor (nitric oxide) has protective actions in the stomach

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacNaughton, W.K.; Wallace, J.L.; Cirino, G.

1989-01-01

The role that nitric oxide, an endothelium-derived relaxing factor, may play in the regulation of gastric mucosal defense was investigated by assessing the potential protective actions of this factor against the damage caused by ethanol in an ex vivo chamber preparation of the rat stomach. Topical application of glyceryl trinitrate and sodium nitroprusside, which have been shown to release nitric oxide, markedly reduced the area of 70% ethanol-induced hemorrhagic damage. Topical application of a 0.01% solution of authentic nitric oxide also significantly reduced the severity of mucosal damage. Pretreatment with indomethacin precluded the involvement of endogenous prostaglandins in the protectivemore » effects of these agents. The protective effects of NO were transient, since a delay of 5 minutes between NO administration and ethanal administration resulted in a complete loss of the protective activity. The protection against ethanol afforded by 10 ug/ml nitroprusside could be completely reversed by intravenous infusion of either 1% methylene blue or 1 mM hemoglobin, both of which inhibit vasodilation induced by nitric oxide. Intravenous infusion of 1% methylene blue significantly increased the susceptibility of the mucosa to damage induced by topical 20% ethanol.« less

Intermittent hydrostatic pressure inhibits shear stress-induced nitric oxide release in human osteoarthritic chondrocytes in vitro.

PubMed

Lee, Mel S; Trindade, Michael C D; Ikenoue, Takashi; Schurman, David J; Goodman, Stuart B; Smith, R Lane

2003-02-01

To test the effects of intermittent hydrostatic pressure (IHP) on nitric oxide (NO) release induced by shear stress and matrix macromolecule gene expression in human osteoarthritic chondrocytes in vitro. Chondrocytes isolated from cartilage samples from 9 patients with osteoarthritis were cultured and exposed to either shear stress or an NO donor. Nitrite concentration was measured using the Griess reaction. Matrix macromolecule mRNA signal levels were determined using reverse-transcriptase polymerase chain reaction and quantified by imaging analysis software. Exposure to shear stress upregulated NO release in a dose and time-dependent manner. Application of IHP inhibited shear stress induced NO release but did not alter NO release from chondrocytes not exposed to shear stress. Shear stress induced NO or addition of an NO donor (sodium nitroprusside) was associated with decreased mRNA signal levels for the cartilage matrix proteins, aggrecan, and type II collagen. Intermittent hydrostatic pressure blocked the inhibitory effects of sodium nitroprusside but did not alter the inhibitory effects of shear stress on cartilage macromolecule gene expression. Our data show that shear stress and IHP differentially alter chondrocyte metabolism and suggest that a balance of effects between different loading forces preserve cartilage extracellular matrix in vivo.

Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose-response relationships and comparison to nitroprusside.

PubMed Central

Jaski, B E; Fifer, M A; Wright, R F; Braunwald, E; Colucci, W S

1985-01-01

Milrinone is a potent positive inotropic and vascular smooth muscle-relaxing agent in vitro, and therefore, it is not known to what extent each of these actions contributes to the drug's hemodynamic effects in patients with heart failure. In 11 patients with New York Heart Association class III or IV congestive heart failure, incremental intravenous doses of milrinone were administered to determine the dose-response relationships for heart rate, systemic vascular resistance, and inotropic state, the latter measured by peak positive left ventricular derivative of pressure with respect to time (dP/dt). To clarify further the role of a positive inotropic action, the relative effects of milrinone and nitroprusside on left ventricular stroke work and dP/dt were compared in each patient at doses matched to cause equivalent reductions in mean arterial pressure or systemic vascular resistance, indices of left ventricular afterload. Milrinone caused heart rate, stroke volume, and dP/dt to increase, and systemic vascular resistance to decrease in a concentration-related manner. At the two lowest milrinone doses resulting in serum concentrations of 63 +/- 4 and 156 +/- 5 ng/ml, respectively, milrinone caused significant increases in stroke volume and dP/dt, but no changes in systemic vascular resistance or heart rate. At the maximum milrinone dose administered (mean serum concentration, 427 +/- 11 ng/ml), heart rate increased from 92 +/- 4 to 99 +/- 4 bpm (P less than 0.01), mean aortic pressure fell from 82 +/- 3 to 71 +/- 3 mmHg (P less than 0.01), right atrial pressure fell from 15 +/- 2 to 7 +/- 1 mmHg (P less than 0.005), left ventricular end-diastolic pressure fell from 26 +/- 3 to 18 +/- 3 (P less than 0.005), stroke volume index increased from 20 +/- 2 to 30 +/- 2 ml/m2 (P less than 0.005), stroke work index increased from 14 +/- 2 to 21 +/- 2 g X m/m2 (P less than 0.01), and dP/dt increased from 858 +/- 54 to 1,130 +/- 108 mmHg/s (P less than 0.005). When compared with nitroprusside for a matched reduction in mean aortic pressure or systemic vascular resistance, milrinone caused a significantly greater increase in stroke work index at the same or lower left ventricular end-diastolic pressure. Milrinone caused a concentration-related increase in dP/dt (32% increase at maximum milrinone dose), whereas nitroprusside had no effect. These data in patients with severe heart failure indicate that in addition to a vasodilating effect, milrinone exerts a concentration-related positive inotropic action that contributes significantly to the drug's overall hemodynamic effects. The positive inotropic action occurs at drug levels that do not exert significant chronotropic or vasodilator effects. Images PMID:3973022

Far Forward Battlefield Telemedicine: Ultrasonic Guidance in Diagnosis and Emergency Therapeutics

DTIC Science & Technology

2008-03-01

Thomas JD, Garcia MJ. Planimetric assessment of anatomic valve area overestimates effective orifice area in bicuspid aortic stenosis . J Am Soc...Popovic ZB, Khot UN, Novaro GM, Casas F, Greenberg NL, Garcia MJ, Francis GS, Thomas JD. Effects of sodium nitroprusside in aortic stenosis ...aneurysmal ventricles,3 aortic regurgitation,4 hypertrophic cardiomyopathy,5 mitral regurgitation,6 ischemic cardiomyopathy,7 and dilated cardiomyopathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osiry, H.; Cano, A.; Reguera, L.

The pentacyanonitrosylferrate complex anion, [Fe(CN){sub 5}NO]{sup 2−}, forms an insoluble solid with Hg(I) ion, of formula unit Hg{sub 2}[Fe(CN){sub 5}NO]·2H{sub 2}O, whose crystal structure and related properties are unknown. This contribution reports the preparation of that compound by the precipitation method and its structural study from X-ray powder patterns complemented with spectroscopic information from IR, Raman, and UV–vis techniques. The crystal structure was solved ab initio and then refined using the Rietveld method. The solid crystallizes with a triclinic unit cell, in the P−1 space group, with cell parameters a=10.1202(12), b=10.1000(13), c=7.4704(11) Å; α=110.664(10), β=110.114(10), γ=104.724(8) °. Within the unitmore » cell, two formula units are accommodated (Z=2). It adopts a layered structure related with the coordination of the equatorial CN groups at their N end to the Hg atoms while the axial CN ligand remains unlinked. Within the layers neighboring Hg{sub 2}[Fe(CN){sub 5}NO] building units remain linked through four relatively strong Hg–Hg interactions, with an interatomic distance of 2.549(3) Å. The charge donation from the equatorial CN groups through their 5σ orbitals results into an increase for the electron density on the Hg atoms, which strengths the Hg–Hg bond. In the Raman spectrum, that metal–metal bond is detected as a stretching vibration band at 167 cm{sup −1}. The available free volume between neighboring layers accommodates two water molecules, which are stabilized within the framework through hydrogen bonds with the N end of the unlinked axial CN group. The removal of these weakly bonded water molecules results in structural disorder for the material 3D framework. - Graphical abstract: Assembling of Hg{sub 2}[Fe(CN){sub 5}NO] units through Hg–Hg interactions. - Highlights: • Homometallic Hg–Hg interactions in metal nitroprusside. • 2D structure supported on metal–metal interactions. • Crystal structure and related properties for mercury (I) nitroprusside. • IR and UV–vis spectral features for mercury (I) nitroprusside.« less

Comparison of non-invasive methods for the assessment of haemodynamic drug effects in healthy male and female volunteers: sex differences in cardiovascular responsiveness.

PubMed Central

Wolzt, M; Schmetterer, L; Rheinberger, A; Salomon, A; Unfried, C; Breiteneder, H; Ehringer, H; Eichler, H G; Fercher, A F

1995-01-01

1. The study was performed to determine the sensitivity and short-term and day-to-day variability of a novel technique based on laser interferometry of ocular fundus pulsations and of non-invasive methods for the quantification of haemodynamic drug effects. An additional aim was to assess sex differences in haemodynamic responsiveness to cardiovascular drugs in male and female healthy volunteers. 2. Ten males and nine females (age range 20-33 years) were studied in a double-blind, randomized, cross-over trial. Simultaneous measurements from systemic haemodynamics, laser interferometry of ocular fundus pulsations, systolic time intervals from mechanocardiography, a/b ratio from oxymetric fingerplethysmography and Doppler sonography of the radial artery were used to describe the haemodynamic effects of cumulative, stepwise increasing intravenous doses of phenylephrine, isoprenaline, sodium nitroprusside and of placebo. 3. Laser interferometry detected the isoprenaline-effects at the lowest dose level of 0.1 micrograms min-1 with a high signal-to-noise ratio. The reproducibility of measurements under baseline was high, no changes were observed after systemically effective doses of phenylephrine or sodium nitroprusside. Systolic time intervals were sensitive and specific for isoprenaline-induced effects, PEP and QS2c-measurements had high reproducibility. Fingerplethysmography proved a sensitive measurement for the detection of the vasodilating effects of sodium nitroprusside, but was not specific, and showed low reproducibility. Measurements from Doppler sonography had lower reproducibility and sensitivity compared with the other applied methods. 4. There was a significant sex difference for several of the haemodynamic parameters under baseline conditions; however, the responsiveness to the drugs under study was not different, when drug effects were expressed as %-change from the baseline. 5. Laser interferometry is a valuable non-invasive, highly sensitive and specific approach for the detection of pulse pressure changes. A battery of non-invasive tests appears useful for the characterization of cardiovascular drugs. Gender differences may not pose a relevant problem for the study of acute haemodynamic effects of cardiovascular drugs. Images Figure 1 PMID:7640140

Far Forward Battlefield Telemedicine: Ultrasonic Guidance in Diagnosis and Emergency Therapeutics

DTIC Science & Technology

2006-08-01

bicuspid aortic stenosis . J Am Soc Echocardiogr. 2005 Dec;18(12):1392-8. 44. Eto Y, Yamada H, Shin JH, Agler DA, Tsujino H, Qin JX, Saracino G, Greenberg...nitroprusside in aortic stenosis associated with severe heart failure: pressure- volume loop analysis using a numerical model. Am J Physiol Heart Circ...3D echocardiography, including exercise and intraoperative (epicardial) examinations, with quantitative validation in aneurysmal ventricles,3 aortic

Activity of nitric oxide-generating compounds against encephalomyocarditis virus.

PubMed Central

Guillemard, E; Geniteau-Legendre, M; Kergot, R; Lemaire, G; Petit, J F; Labarre, C; Quero, A M

1996-01-01

Nitric oxide (NO) generated by two NO donors (sodium nitroprusside or S-nitroso-L-glutathione) was shown to exert a dose-dependent inhibition of encephalomyocarditis virus growth in L-929 cells. This activity was not due to the cytotoxic or direct virucidal effects of NO donors. L-929 cells were shown to produce NO endogenously, but this low level of production did not counter encephalomyocarditis virus replication. PMID:8849231

Comparative study on the inhibitory effect of caffeic and chlorogenic acids on key enzymes linked to Alzheimer's disease and some pro-oxidant induced oxidative stress in rats' brain-in vitro.

PubMed

Oboh, Ganiyu; Agunloye, Odunayo M; Akinyemi, Ayodele J; Ademiluyi, Adedayo O; Adefegha, Stephen A

2013-02-01

This study sought to investigate and compare the interaction of caffeic acid and chlorogenic acid on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and some pro-oxidants (FeSO(4), sodium nitroprusside and quinolinic acid) induced oxidative stress in rat brain in vitro. The result revealed that caffeic acid and chlorogenic acid inhibited AChE and BChE activities in dose-dependent manner; however, caffeic acid had a higher inhibitory effect on AChE and BChE activities than chlorogenic acid. Combination of the phenolic acids inhibited AChE and BChE activities antagonistically. Furthermore, pro-oxidants such as, FeSO(4), sodium nitroprusside and quinolinic acid caused increase in the malondialdehyde (MDA) contents of the brain which was significantly decreased dose-dependently by the phenolic acids. Inhibition of AChE and BChE activities slows down acetylcholine and butyrylcholine breakdown in the brain. Therefore, one possible mechanism through which the phenolic acids exert their neuroprotective properties is by inhibiting AChE and BChE activities as well as preventing oxidative stress-induced neurodegeneration. However, esterification of caffeic acid with quinic acid producing chlorogenic acid affects these neuroprotective properties.

The relaxant actions of ethanolic extract of Tridax procumbens (Linn.) on rat corpus cavernosum smooth muscle contraction.

PubMed

Salahdeen, Hussein M; Idowu, Gbolahan O; Yemitan, Omoniyi K; Murtala, Babatunde A; Alada, Abdul Rasak A

2015-03-01

The effect of Tridax procumbens aqueous ethanolic extract on the rat corpus cavernosum smooth muscles was evaluated in the present study. Corpus cavernosum strips obtained from healthy, young, adult male Wistar albino rats (250-300 g) were precontracted with phenylephrine (10-7 M) or KCl (60 mM) and then treated with various concentrations of T. procumbens extract (0.15-1.05 mg/mL). The change in corpus cavernosum strip tension was recorded. The interactions between T. procumbens extract with acetylcholine and with sodium nitroprusside were also evaluated. The results indicated that corpus cavernosum strips relaxation induced by T. procumbens extract was concentration-dependent and this was significant (p<0.5). Pre-treatment with a nitric oxide synthase (NOS) inhibitor (N(1) nitro-L-arginine-methyl ester, l-NAME), did not completely inhibit the relaxation. However, T. procumbens extract (0.6 mg/mL) significantly (p<0.5) enhanced both acetylcholine- and sodium nitroprusside-induced corpus cavernosum strips relaxation. RESULTS suggest that T. procumbens extract has a concentration-dependent relaxant effect on the isolated rat corpus cavernosum. The mechanism of action of T. procumbens extract is complex. A part of its relaxing effect is mediated directly by the release of NO from endothelium which may improve erectile dysfunction.

Nafion/lead nitroprusside nanoparticles modified carbon ceramic electrode as a novel amperometric sensor for L-cysteine.

PubMed

Razmi, H; Heidari, H

2009-05-01

This work describes the electrochemical and electrocatalytic properties of carbon ceramic electrode (CCE) modified with lead nitroprusside (PbNP) nanoparticles as a new electrocatalyst material. The structure of deposited film on the CCE was characterized by energy dispersive X-ray (EDX), Fourier transform infrared (FTIR), and scanning electron microscopy (SEM). The cyclic voltammogram (CV) of the PbNP modified CCE showed two well-defined redox couples due to [Fe(CN)5NO](3-)/[Fe(CN)5NO](2-) and Pb(IV)/Pb(II) redox reactions. The modified electrode showed electrocatalytic activity toward the oxidation of L-cysteine and was used as an amperometric sensor. Also, to reduce the fouling effect of L-cysteine and its oxidation products on the modified electrode, a thin film of Nafion was coated on the electrode surface. The sensor response was linearly changed with L-cysteine concentration in the range of 1 x 10(-6) to 6.72 x 10(-5)mol L(-1) with a detection limit (signal/noise ratio [S/N]=3) of 0.46 microM. The sensor sensitivity was 0.17 microA (microM)(-1), and some important advantages such as simple preparation, fast response, good stability, interference-free signals, antifouling properties, and reproducibility of the sensor for amperometric determination of L-cysteine were achieved.

Allopurinol improves endothelial dysfunction in chronic heart failure.

PubMed

Farquharson, Colin A J; Butler, Robert; Hill, Alexander; Belch, Jill J F; Struthers, Allan D

2002-07-09

Increased oxidative stress in chronic heart failure is thought to contribute to endothelial dysfunction. Xanthine oxidase produces oxidative stress and therefore we examined whether allopurinol improved endothelial dysfunction in chronic heart failure. We performed a randomized, placebo-controlled, double-blind crossover study on 11 patients with New York Heart Association class II-III chronic heart failure, comparing 300 mg allopurinol daily (1 month) versus placebo. Endothelial function was assessed by standard forearm venous occlusion plethysmography with acetylcholine, nitroprusside, and verapamil. Plasma malondialdehyde levels were also compared to assess significant changes in oxidative stress. Allopurinol significantly increased the forearm blood flow response to acetylcholine (percentage change in forearm blood flow [mean+/-SEM]: 181+/-19% versus 120+/-22% allopurinol versus placebo; P=0.003). There were no significant differences in the forearm blood flow changes between the placebo and allopurinol treatment arms with regard to sodium nitroprusside or verapamil. Plasma malondialdehyde was significantly reduced with allopurinol treatment (346+/-128 nmol/L versus 461+/-101 nmol/L, allopurinol versus placebo; P=0.03), consistent with reduced oxidative stress with allopurinol therapy. We have shown that allopurinol improves endothelial dysfunction in chronic heart failure. This raises the distinct possibility that allopurinol might reduce cardiovascular events and even improve exercise capacity in chronic heart failure.

Sodium nitroprusside affects the level of photosynthetic enzymes and glucose metabolism in Phaseolus aureus (mung bean).

PubMed

Lum, Hon-Kei; Lee, Chi-Ho; Butt, Yoki Kwok-Chu; Lo, Samuel Chun-Lap

2005-06-01

Nitric oxide (NO) is an important signaling molecule in plants. The present study aims to investigate the downstream signaling pathways of NO in plants using a proteomic approach. Phaseolus aureus (mung bean) leaf was treated with sodium nitroprusside (SNP), which releases nitric oxide in the form of nitrosonium cation (NO+) upon light irradiation. Changes in protein expression profiles of the SNP treated mung bean leaf were analyzed by two-dimensional gel electrophoresis (2-DE). Comparison of 2-DE electropherograms revealed seven down-regulated and two up-regulated proteins after treatment with 0.5 mM SNP for 6 h. The identities of these proteins were analyzed by a combination of peptide mass fingerprinting and post-source decay using a matrix-assisted-laser-desorption-ionisation-time-of-flight (MALDI-TOF) mass spectrometer. Six out of these nine proteins found are involved in either photosynthesis or cellular metabolism. We have taken our investigation further by studying the effect of NO+ on glucose contents in mung bean leaves. Our results clearly demonstrated that NO+ rapidly and drastically decrease the amount of glucose in mung bean leaves. Moreover, four out of nine of these proteins are chloroplastic isoforms. These results suggested that chloroplasts might be one of the main sub-cellular targets of NO in plants.

Effect of isoproterenol, phenylephrine, and sodium nitroprusside on fundus pulsations in healthy volunteers.

PubMed

Schmetterer, L; Wolzt, M; Salomon, A; Rheinberger, A; Unfried, C; Zanaschka, G; Fercher, A F

1996-03-01

Recently a laser interferometric method for topical measurement of fundus pulsations has been developed. Fundus pulsations in the macular region are caused by the inflow and outflow of blood into the choroid. The purpose of this work was to study the influence of a peripheral vasoconstricting (the alpha 1 adrenoceptor agonist phenylephrine), a predominantly positive inotropic (the non-specific beta adrenoceptor agonist isoproterenol), and a non-specific vasodilating (sodium nitroprusside) model drug on ocular fundus pulsations to determine reproducibility and sensitivity of the method. In a double masked randomised crossover study the drugs were administered in stepwise increasing doses to 10 male and nine female healthy volunteers. Systemic haemodynamic variables and fundus pulsations were measured at all infusion steps. Fundus pulsation increased during infusion of isoproterenol with statistical significance versus baseline at the lowest dose of 0.1 microgram/min. Neither peripheral vasoconstriction nor peripheral vasodilatation affected the ocular fundus pulsations. Measurements of fundus pulsations is a highly reproducible method in healthy subjects with low ametropy. Changes of local pulsatile ocular blood flow were detectable with our method following the infusion of isoproterenol. As systemic pharmacological vasodilatation or vasoconstriction did not change fundus pulsations, further experimental work has to be done to evaluate the sensitivity of the laser interferometric fundus pulsation measurement in various eye diseases.

Human recombinant soluble guanylyl cyclase: expression, purification, and regulation

NASA Technical Reports Server (NTRS)

Lee, Y. C.; Martin, E.; Murad, F.

2000-01-01

The alpha1- and beta1-subunits of human soluble guanylate cyclase (sGC) were coexpressed in the Sf9 cells/baculovirus system. In addition to the native enzyme, constructs with hexahistidine tag at the amino and carboxyl termini of each subunit were coexpressed. This permitted the rapid and efficient purification of active recombinant enzyme on a nickel-affinity column. The enzyme has one heme per heterodimer and was readily activated with the NO donor sodium nitroprusside or 3-(5'-hydroxymethyl-2'furyl)-1-benzyl-indazole (YC-1). Sodium nitroprusside and YC-1 treatment potentiated each other in combination and demonstrated a remarkable 2,200-fold stimulation of the human recombinant sGC. The effects were inhibited with 1H-(1,2, 4)oxadiazole(4,3-a)quinoxalin-1one (ODQ). The kinetics of the recombinant enzyme with respect to GTP was examined. The products of the reaction, cGMP and pyrophosphate, inhibited the enzyme. The extent of inhibition by cGMP depended on the activation state of the enzyme, whereas inhibition by pyrophosphate was not affected by the enzyme state. Both reaction products displayed independent binding and cooperativity with respect to enzyme inhibition. The expression of large quantities of active enzyme will facilitate structural characterization of the protein.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krall, J.F.; Morin, A.

Cells growing in culture with previously described properties of rat uterine smooth muscle accumulated /sup 45/Ca/sup 2 +/ from the medium. Ca/sup 2 +/ uptake by these cells was stimulated by the addition to the medium of 8-bromo-cGMP but not by 8-bromo-cAMP. Ca/sup 2 +/ uptake was also stimulated by carbachol and by the nitro-vasodilator nitroprusside. Although cholinergic agonists have been shown previously to stimulate contraction but not cGMP synthesis in the rat myometrium, both carbachol and nitroprusside stimulated cGMP production by the cultured cells. These results suggested the cells had cholinergic receptor-medicated functions that reflected some neurotransmitter-sensitive properties ofmore » uterine smooth muscle in situ. When determined by a specific radioligand binding assay, subcellular fractions of the cultured cells bound muscarinic cholinergic agonists and antagonists with affinities expected of the muscarinic receptor. The cells were also sensitive to the ..beta..-adrenergic catecholamine agonist isoproterenol, which stimulated cAMP production but not Ca/sup 2 +/ uptake. Carbachol failed to inhibit isoproterenol-dependent cAMP production, which is an important property of the cholinergic receptor in uterine smooth muscle in situ. These results suggest some but not all acetylcholine-sensitive properties of uterine smooth muscle may be retained in cell culture.« less

Effects of sodium nitroprusside (SNP) pretreatment on UV-B stress tolerance in lettuce (Lactuca sativa L.) seedlings.

PubMed

Esringu, Aslıhan; Aksakal, Ozkan; Tabay, Dilruba; Kara, Ayse Aydan

2016-01-01

Ultraviolet-B (UV-B) radiation is one of the most important abiotic stress factors that could influence plant growth, development, and productivity. Nitric oxide (NO) is an important plant growth regulator involved in a wide variety of physiological processes. In the present study, the possibility of enhancing UV-B stress tolerance of lettuce seedlings by the exogenous application of sodium nitroprusside (SNP) was investigated. UV-B radiation increased the activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), peroxidase (POD) and total phenolic concentrations, antioxidant capacity, and expression of phenylalanine ammonia lyase (PAL) gene in seedlings, but the combination of SNP pretreatment and UV-B enhanced antioxidant enzyme activities, total phenolic concentrations, antioxidant capacity, and PAL gene expression even more. Moreover, UV-B radiation significantly inhibited chlorophylls, carotenoid, gibberellic acid (GA), and indole-3-acetic acid (IAA) contents and increased the contents of abscisic acid (ABA), salicylic acid (SA), malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide radical (O2•(-)) in lettuce seedlings. When SNP pretreatment was combined with the UV-B radiation, we observed alleviated chlorophylls, carotenoid, GA, and IAA inhibition and decreased content of ABA, SA, MDA, H2O2, and O2•(-) in comparison to non-pretreated stressed seedlings.

Hypertensive crisis.

PubMed

Rodriguez, Maria Alexandra; Kumar, Siva K; De Caro, Matthew

2010-01-01

Hypertension is a common chronic medical condition affecting over 65 million Americans. Uncontrolled hypertension can progress to a hypertensive crisis defined as a systolic blood pressure >180 mm Hg or a diastolic blood pressure >120 mm Hg. Hypertensive crisis can be further classified as a hypertensive urgency or hypertensive emergency depending on end-organ involvement including cardiac, renal, and neurologic injury. The prompt recognition of a hypertensive emergency with the appropriate diagnostic tests and triage will lead to the adequate reduction of blood pressure, ameliorating the incidence of fatal outcomes. Severely hypertensive patients with acute end-organ damage (hypertensive emergencies) warrant admission to an intensive care unit for immediate reduction of blood pressure with a short-acting titratable intravenous antihypertensive medication. Hypertensive urgencies (severe hypertension with no or minimal end-organ damage) may in general be treated with oral antihypertensives as an outpatient. Rapid and short-lived intravenous medications commonly used are labetalol, esmolol, fenoldopam, nicardipine, sodium nitroprusside, and clevidipine. Medications such as hydralazine, immediate release nifedipine, and nitroglycerin should be avoided. Sodium nitroprusside should be used with caution because of its toxicity. The risk factors and prognosticators of a hypertensive crisis are still under recognized. Physicians should perform complete evaluations in patients who present with a hypertensive crisis to effectively reverse, intervene, and correct the underlying trigger, as well as improve long-term outcomes after the episode.

Management of Patients With Hypertensive Urgencies and Emergencies

PubMed Central

Cherney, David; Straus, Sharon

2002-01-01

BACKGROUND Hypertensive urgencies and emergencies are common clinical occurrences in hypertensive patients. Treatment practices vary considerably to because of the lack of evidence supporting the use of one therapeutic agent over another. This paper was designed to review the evidence for various pharmacotherapeutic regimens in the management of hypertensive urgencies and emergencies, in terms of the agents' abilities to reach predetermined “safe” goal blood pressures (BPs), and to prevent adverse events. METHODS medline was searched from 1966 to 2001, and the reference lists of all the articles were retrieved and searched for relevant references, and experts in the field were contacted to identify other relevant studies. The Cochrane Library was also searched. Studies that were eligible for inclusion in this review were systematic reviews of randomized control trials (RCTs) and individual RCTs, all-or-none studies, systematic reviews of cohort studies and individual cohort studies, and outcomes research. No language restrictions were used. RESULTS None of the trials included in this review identified an optimal rate of BP lowering in hypertensive emergencies and urgencies. The definitions of hypertensive emergencies and urgencies were not consistent, but emergencies always involved target end-organ damage, and urgencies were without such damage. Measures of outcome were not uniform between studies. The 4 hypertensive emergency and 15 hypertensive urgency studies represented 236 and 1,074 patients, respectively. The evidence indicated a nonsignificant trend toward increased efficacy with urapidil compared to nitroprusside for hypertensive emergencies (number needed to treat [NNT] for urapidil to achieve target BP, 12; 95% confidence interval [95% CI], number of patients needed to harm [NNH], 5 to NNT, 40 compared to nitroprusside). Several medications were efficacious in treating hypertensive urgencies, including: nicardipine (NNT for nicardipine compared to plabebo, 2 in one study [95% CI, 1 to 5] and 1 in another [95% CI, 1 to 1]); lacidipine (NNT, 2; 95% CI, 1 to 8 for lacidipine vs nifedipine) or urapidil (NNT for urapidil compared to enalaprilat and nifedipine, 4; 95% CI, 3 to 6); and nitroprusside and fenoldopam (all patients reached target BP in 2 studies). The studies reported 2 cases of cerebral ischemia secondary to nifedipine. CONCLUSIONS Many effective agents exist for the treatment of hypertensive crises. Because of the lack of large randomized controlled trials, many questions remain unanswered, such as follow-up times and whether any of the studied agents have mortality benefit. PMID:12472930

Artemisinin conferred ERK mediated neuroprotection to PC12 cells and cortical neurons exposed to sodium nitroprusside-induced oxidative insult.

PubMed

Zheng, Wenhua; Chong, Cheong-Meng; Wang, Haitao; Zhou, Xuanhe; Zhang, Lang; Wang, Rikang; Meng, Qian; Lazarovici, Philip; Fang, Jiankang

2016-08-01

The production of nitric oxide (NO) is one of the primary mediators of ischemic damage, glutamate neurotoxicity and neurodegeneration and therefore inhibition of NO-induced neurotoxicity may be considered a therapeutic target for reducing neuronal cell death (neuroprotection). In this study, artemisinin, a well-known anti-malaria drug was found to suppress sodium nitroprusside (SNP, a nitric oxide donor)-induced cell death in the PC12 cells and brain primary cortical neuronal cultures. Pretreatment of PC12 cells with artemisinin significantly suppressed SNP-induced cell death by decreasing the extent of oxidation, preventing the decline of mitochondrial membrane potential, restoring abnormal changes in nuclear morphology and reducing lactate dehydrogenase release and inhibiting caspase 3/7 activities. Western blotting analysis revealed that artemisinin was able to activate extracellular regulated protein kinases (ERK) pathway. Furthermore, the ERK inhibitor PD98059 blocked the neuroprotective effect of artemisinin whereas the PI3K inhibitor LY294002 had no effect. Cumulatively these findings support the notion that artemisinin confers neuroprotection from SNP-induce neuronal cell death insult, a phenomenon coincidentally related to activation of ERK phosphorylation. This SNP-induced oxidative insult in PC12 cell culture model may be useful to investigate molecular mechanisms of NO-induced neurotoxicity and drug-induced neuroprotection, and to generate novel therapeutic concepts for ischemic disease treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Huperzine A derivative M3 protects PC12 cells against sodium nitroprusside-induced apoptosis

PubMed Central

Ning, Na; Hu, Jin-feng; Yuan, Yu-he; Zhang, Xin-yuan; Dai, Jun-gui; Chen, Nai-hong

2012-01-01

Aim: To investigate the effects of M3, a derivative of huperzine A, on the apoptosis induced by sodium nitroprusside (SNP) in PC12 cells. Methods: Cell viability was detected using MTT method. Apoptosis was examined with annexin V/prodium iodide (PI) stain. The levels of reactive oxygen species (ROS) were measured using fluorophotometric quantitation. The amount of malonaldehyde (MDA) was determined with MDA detection kits. The expression of caspase-3 and Hsp70 were analyzed using Western blotting. Results: Exposure of PC12 cells to SNP (200 μmol/L) for 24 h decreased the cell viability to 69.0% of that in the control group. Pretreatment with M3 (10 μmol/L) or huperzine A (10 μmol/L) significantly protected the cells against SNP-induced injury and apoptosis; the ratio of apoptotic bodies in PC12 cells was decreased from 27.3% to 15.0%. Pretreatment with M3 (10 μmol/L) significantly decreased ROS and MDA levels, and increased the expression of Hsp70 in the cells. Quercetin (10 μmol/L) blocked the protective effect of M3, while did not influence on that of huperzine A. Conclusion: M3 protects PC12 cells against SNP-induced apoptosis, possible due to ROS scavenging and Hsp70 induction. PMID:22120967

Nitric oxide signaling pathway regulates potassium chloride cotransporter-1 mRNA expression in vascular smooth muscle cells.

PubMed

Di Fulvio, M; Lauf, P K; Adragna, N C

2001-11-30

Rat vascular smooth muscle cells (VSMCs) express at least two mRNAs for K-Cl cotransporters (KCC): KCC1 and KCC3. cGMP-dependent protein kinase I regulates KCC3 mRNA expression in these cells. Here, we show evidence implicating the nitric oxide (NO)/cGMP signaling pathway in the expression of KCC1 mRNA, considered to be the major cell volume regulator. VSMCs, expressing soluble guanylyl cyclase (sGC) and PKG-I isoforms showed a time- and concentration-dependent increase in KCC1 mRNA levels after treatment with sodium nitroprusside as demonstrated by semiquantitative RT-PCR. sGC-dependent regulation of KCC1 mRNA expression was confirmed using YC-1, a NO-independent sGC stimulator. The sGC inhibitor LY83583 blocked the effects of sodium nitroprusside and YC-1. Moreover, 8-Br-cGMP increased KCC1 mRNA expression in a concentration- and time-dependent fashion. The 8-Br-cGMP effect was partially blocked by KT5823 but not by actinomycin D. However, actinomycin D and cycloheximide increased basal KCC1 mRNA in an additive manner, suggesting different mechanisms of action for both drugs. These findings suggest that in VSMCs, the NO/cGMP-signaling pathway participates in KCC1 mRNA regulation at the post-transcriptional level.

Effect of L-arginine on the relaxation caused by sodium nitroprusside on isolated rat renal artery.

PubMed

Orescanin, Z; Milovanović, S R

2006-12-01

In the present study we investigated the mechanism of nitric oxide induced relaxation of renal arteries, with or without endothelium, taken from normotensive and spontaneously hypertensive (SH) rats. With this purpose in mind, the effects of the nitric oxide donor, sodium nitroprusside (SNP), with and without L-arg in the medium, on isolated rat renal artery relaxation were studied. Relaxing effect of SNP was higher in normotensive (10(-5) M of SNP caused 220% of relaxation in the cases with endothelium and 240% without endothelium), in comparison with SH rats (100% of relaxation with endothelium and 150% without). L-arg antagonized the relaxing effect of SNP in the examined renal arteries, more in normotensive (100-160% with endothelium and 110-195% without) than in hypertensive ones (0-10% with endothelium and 35-75% without) at SNP concentrations 10(-7) - 10(-5) M, respectively (*P < 0.05; **P < 0.001). L-arg did not significantly change relaxing effect of SNP in the isolated renal arteries with endothelium taken from SH rats, which show that L-arg, by modifying the chemical versatility of NO into redox active forms -nitrosonium (NO+) and -nitroxyl (NO-), produces different relaxing effects in normotensive and hypertensive isolated arteries of rats, with or without endothelium, potentiating the role of nitroxyl induced relaxation in SH rats.

Effect of isoproterenol, phenylephrine, and sodium nitroprusside on fundus pulsations in healthy volunteers.

PubMed Central

Schmetterer, L; Wolzt, M; Salomon, A; Rheinberger, A; Unfried, C; Zanaschka, G; Fercher, A F

1996-01-01

AIMS/BACKGROUND: Recently a laser interferometric method for topical measurement of fundus pulsations has been developed. Fundus pulsations in the macular region are caused by the inflow and outflow of blood into the choroid. The purpose of this work was to study the influence of a peripheral vasoconstricting (the alpha 1 adrenoceptor agonist phenylephrine), a predominantly positive inotropic (the non-specific beta adrenoceptor agonist isoproterenol), and a non-specific vasodilating (sodium nitroprusside) model drug on ocular fundus pulsations to determine reproducibility and sensitivity of the method. METHODS: In a double masked randomised crossover study the drugs were administered in stepwise increasing doses to 10 male and nine female healthy volunteers. Systemic haemodynamic variables and fundus pulsations were measured at all infusion steps. RESULTS: Fundus pulsation increased during infusion of isoproterenol with statistical significance versus baseline at the lowest dose of 0.1 microgram/min. Neither peripheral vasoconstriction nor peripheral vasodilatation affected the ocular fundus pulsations. CONCLUSIONS: Measurements of fundus pulsations is a highly reproducible method in healthy subjects with low ametropy. Changes of local pulsatile ocular blood flow were detectable with our method following the infusion of isoproterenol. As systemic pharmacological vasodilatation or vasoconstriction did not change fundus pulsations, further experimental work has to be done to evaluate the sensitivity of the laser interferometric fundus pulsation measurement in various eye diseases. PMID:8703859

Isometric responses of isolated intrapulmonary bronchioles from cats with and without adult heartworm infection.

PubMed

Wooldridge, Anne A; Dillon, A Ray; Tillson, D Michael; Zhong, Qiao; Barney, Sharron R

2012-03-01

To determine the isometric responses of isolated intrapulmonary bronchioles from cats with and without adult heartworm infection. 13 purpose-bred adult cats. Cats were infected with 100 third-stage larvae or received a sham inoculation, and the left caudal lung lobe was collected 278 to 299 days after infection. Isometric responses of intrapulmonary bronchiolar rings were studied by use of a wire myograph. Three cycles of contractions induced by administration of 10 μM acetylcholine were followed by administration of the contractile agonists acetylcholine, histamine, and 5-hydroxy-tryptamine. To evaluate relaxation, intrapulmonary bronchiolar rings were constricted by administration of 10 μM 5-hydroxytryptamine, and concentration-response curves were generated from administration of sodium nitroprusside, isoproterenol, and substance P. Compared with tissues from control cats, contractile responses to acetylcholine and 5-hydroxytryptamine were reduced in tissues from heartworm-infected cats. Relaxation to isoproterenol was significantly reduced in tissues from heartworm-infected cats. Relaxation to substance P was increased in tissues from heartworm-infected cats, but relaxation to sodium nitroprusside was unchanged. Results suggested that despite increased bronchiolar wall thickness in heartworm-infected cats, a hyperreactive response of the bronchiolar smooth muscle is not the primary mechanism of respiratory tract clinical signs. Reduced response of the airway to isoproterenol may indicate refractoriness to bronchiolar relaxation in heartworm-infected cats.

Dilator and constrictor response of renal vasculature during acute renal hypotension in anesthetized goats. Role of nitric oxide.

PubMed

Diéguez, Godofredo; García-Villalón, Angel Luis

2011-01-01

The relative role of NO derived from endothelium NO synthase (eNOS) and neuronal NO synthase (nNOS) in renovascular reactivity during renal hypotension is unknown. To examine this issue, we recorded the effects of unspecific inhibitor of NO synthase N(w)-nitro-L-arginine methyl esther (L-NAME) and inhibitor of nNOS 7-nitroindazole monosodium salt (7-NINA) on renal vasodilator and vasoconstrictor responses in anesthetized goats during renal hypotension by constricting the abdominal aorta. Intrarenal administration of L-NAME and hypotension, either untreated or treated with L-NAME, decreased resting renal blood flow, and the increases in renal blood flow by acetylcholine but not those by sodium nitroprusside were tempered, and the decreases by norepinephrine and angiotensin II were augmented. Intraperitoneal administration of 7-NINA did not affect, and 7-NINA+hypotension decreased renal blood flow, and under these conditions the increases in renal blood flow by acetylcholine and sodium nitroprusside were not modified, and the decreases by norepinephrine and angiotensin II were slightly (during 7-NINA) or consistently augmented (7-NINA+hypotension). Therefore, NO derived from eNOS plays a significant role, while that derived from nNOS plays a little role, if any, to regulate renal blood flow and to mediate acetylcholine-induced vasodilation, as well to modulate renal vasoconstriction by norepinephrine and angiotensin II. Copyright © 2011 Elsevier Inc. All rights reserved.

Sodium nitroprusside is effective in preventing and/or reversing the development of schizophrenia-related behaviors in an animal model: The SHR strain.

PubMed

Diana, Mariana C; Peres, Fernanda F; Justi, Veronica; Bressan, Rodrigo A; Lacerda, Acioly L T; Crippa, José Alexandre; Hallak, Jaime E C; Abilio, Vanesssa Costhek

2018-04-14

The treatment of schizophrenia with antipsychotics is still unsatisfactory. Therefore, the search for new treatments and prevention is crucial, and animal models are fundamental tools for this objective. Preclinical and clinical data evidence the antipsychotic profile of sodium nitroprusside (SNP), a nitric oxide (NO) donor. We aimed to investigate SNP in treating and/or preventing the schizophrenia-related behaviors presented by the spontaneously hypertensive rats (SHR) strain. Wistar rats (WR) and SHRs were submitted to two schemes of treatment: (i) a single injection of SNP or vehicle in adulthood; (ii) a long-term early treatment from 30 to 60 postnatal day with SNP or vehicle. The following behaviors were evaluated 24 hours after the acute treatment or 30 days after the long-term treatment: locomotion, social interaction, and contextual fear conditioning. Spontaneously hypertensive rats presented hyperlocomotion, decreased social interaction, and impaired contextual fear conditioning. Single injection of SNP decreased social interaction in both strains and induced a deficit in contextual fear conditioning in WR. Oppositely, early treatment with SNP prevented the behavioral abnormalities in adult SHRs without promoting any effects in WR. Our preclinical data point to SNP as a preventive and safe strategy with a broad range of effectiveness to the positive, negative, and cognitive symptoms of schizophrenia. © 2018 John Wiley & Sons Ltd.

Safety and efficacy of intravenous labetalol for hypertensive crisis in infants and small children.

PubMed

Thomas, Christopher A; Moffett, Brady S; Wagner, Jeffrey L; Mott, Antonio R; Feig, Daniel I

2011-01-01

To determine the efficacy and safety of labetalol for hypertensive crisis in children ≤ 24 months of age. Retrospective chart review. Statistical analysis utilized analysis of variance for continuous data, chi-square tests for nominal data, and linear regression. A 737-bed pediatric teaching institution. Twenty-seven patients ≤ 24 months of age were treated with 37 intravenous infusions of labetalol, nicardipine, or nitroprusside for hypertensive crisis or hypertensive urgency. None. The primary end point consisted of time to 20% reduction in systolic blood pressure. Primary safety end points measured the prevalence of deleterious effects of labetalol. Continuous infusion of labetalol reduced mean systolic blood pressure by at least 20% in < 8 hrs. This effect was similar to nicardipine and nitroprusside infusions. The reported side effects were similar in each group. Patients receiving labetalol and presenting with ischemic or traumatic brain injury were likely to develop hypotension requiring infusion discontinuation. Continuous intravenous labetalol infusion is efficacious for treatment of hypertensive crisis in children ≤ 24 months of age. Aside from patients presenting with ischemic or traumatic brain injury, labetalol was safe to use in this population for hypertensive emergencies and had a satisfactory adverse effect profile. Labetalol may reach dose saturation at a much lower dose in young children in comparison to adults. Clinicians should use caution when initiating labetalol infusions in young patients with brain injury.

Effects of sodium nitroprusside on splanchnic microcirculation in a resuscitated porcine model of septic shock.

PubMed

Assadi, A; Desebbe, O; Kaminski, C; Rimmelé, T; Bénatir, F; Goudable, J; Chassard, D; Allaouchiche, B

2008-01-01

We tested the hypothesis that sodium nitroprusside (SNP) might improve the impairment of hepatosplanchnic microcirculatory blood flow (MBF) in septic shock. Fourteen pigs were anaesthetized and their lungs mechanically ventilated. Sepsis was induced with i.v. infusion of live Pseudomonas aeruginosa [1x10(8) colony forming units (CFU) ml(-1) kg(-1)] for 1 h. Sixty minutes later, the animals received in a random succession either SNP or normal saline for 30 min. Mean arterial pressure (MAP), cardiac index (CI), mean pulmonary artery pressure (MPAP), carbon dioxide tension of the ileal mucosa (PCO2; by gas tonometry), ileal mucosal and hepatic MBF by laser Doppler flowmetry, blood gases, and lactates were assessed before, during administration, and 30 min after discontinuing the test drug. Bacterial infusion promoted hypodynamic shock (MAP -18%, CI -33%, ileal MBF -19%, and hepatic MBF -27%), which was converted to normodynamic shock by resuscitation. During SNP infusion, ileal mucosal MBF significantly increased (+19%) compared with control (P = 0.033). Although hepatic MBF increased (+42% from baseline), this did not differ from control. In order to maintain a constant central venous pressure and MAP, fluid loading and norepinephrine (P < 0.01) were increased. Acid-base status was not altered by SNP. In a resuscitated porcine model of the early phase of septic shock, SNP improved ileal mucosal MBF but required a concomitant increase in fluid and norepinephrine supplements to maintain constant systemic haemodynamic parameters.

Local antinociceptive action of fluoxetine in the rat formalin assay: role of l-arginine/nitric oxide/cGMP/KATP channel pathway.

PubMed

Ghorbanzadeh, Behnam; Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Alboghobeish, Soheila

2018-02-01

The present study was conducted to evaluate the local antinociceptive actions of fluoxetine, a selective serotonin reuptake inhibitor, and the possible involvement of the l-arginine/NO/cGMP/K ATP channel pathway in this effect using the formalin test in rats. To elucidate the underlying mechanisms, animals were pre-treated with l-NAME, aminoguanidine, methylene blue, glibenclamide, l-arginine, sodium nitroprusside, or diazoxide. Local ipsilateral, but not contralateral, administration of fluoxetine (10-300 μg/paw) dose-dependently suppressed flinching number during both early and late phases of the test, and this was comparable with morphine also given peripherally. Pre-treatment with l-NAME, aminoguanidine, methylene blue, or glibenclamide dose-dependently prevented fluoxetine (100 μg/paw)-induced antinociception in the late phase. In contrast, administration of l-arginine, sodium nitroprusside, and diazoxide significantly enhanced the antinociception caused by fluoxetine in the late phase of the test. However, these treatments had no significant effect on the antinociceptive response of fluoxetine in the early phase of the formalin test. Our data demonstrate that local peripheral antinociception of fluoxetine during the late phase of the formalin test could be due to activation of l-arginine/NO/cGMP/K ATP channel pathway. The peripheral action of fluoxetine raises the possibility that topical application of this drug (e.g., as a cream, ointment, or jelly) may be a useful method for relieving the inflammatory pain states.

Baroreflex buffering and susceptibility to vasoactive drugs

NASA Technical Reports Server (NTRS)

Jordan, Jens; Tank, Jens; Shannon, John R.; Diedrich, Andre; Lipp, Axel; Schroder, Christoph; Arnold, Guy; Sharma, Arya M.; Biaggioni, Italo; Robertson, David;

Vildagliptin Improves Endothelium-Dependent Vasodilatation in Type 2 Diabetes

PubMed Central

van Poppel, Pleun C.M.; Netea, Mihai G.; Smits, Paul; Tack, Cees J.

2011-01-01

OBJECTIVE To investigate whether the dipeptidyl peptidase-4 inhibitor vildagliptin improves endothelium-dependent vasodilatation in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Sixteen subjects with type 2 diabetes (age 59.8 ± 6.8 years, BMI 29.1 ± 4.8 kg/m2, HbA1c 6.97 ± 0.61) on oral blood glucose–lowering treatment were included. Participants received vildagliptin 50 mg b.i.d. or acarbose 100 mg t.i.d. for four consecutive weeks in a randomized, double-blind, cross-over design. At the end of each treatment period, we measured forearm vasodilator responses to intra-arterially administered acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator). RESULTS Infusion of acetylcholine induced a dose-dependent increase in forearm blood flow in the experimental arm, which was higher during vildagliptin (3.1 ± 0.7, 7.9 ± 1.1, and 12.6 ± 1.4 mL ⋅ dL−1 ⋅ min−1 in response to three increasing dosages of acetylcholine) than during acarbose (2.0 ± 0.7, 5.0 ± 1.2, and 11.7 ± 1.6 mL ⋅ dL−1 ⋅ min−1, respectively; P = 0.01 by two-way ANOVA). Treatment with vildagliptin did not significantly change the vascular responses to sodium nitroprusside. CONCLUSIONS Four weeks’ treatment with vildagliptin improves endothelium-dependent vasodilatation in subjects with type 2 diabetes. This observation might have favorable cardiovascular implications. PMID:21788633

Role of nitric oxide in adenosine-induced vasodilation in humans

NASA Technical Reports Server (NTRS)

Costa, F.; Biaggioni, I.; Robertson, D. (Principal Investigator)

1998-01-01

Vasodilation is one of the most prominent effects of adenosine and one of the first to be recognized, but its mechanism of action is not completely understood. In particular, there is conflicting information about the potential contribution of endothelial factors. The purpose of this study was to explore the role of nitric oxide in the vasodilatory effect of adenosine. Forearm blood flow responses to intrabrachial adenosine infusion (125 microg/min) were assessed with venous occlusion plethysmography during intrabrachial infusion of saline or the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) (12.5 mg/min). Intrabrachial infusions of acetylcholine (50 microg/min) and nitroprusside (3 microg/min) were used as a positive and negative control, respectively. These doses were chosen to produce comparable levels of vasodilation. In a separate study, a second saline infusion was administered instead of L-NMMA to rule out time-related effects. As expected, pretreatment with L-NMMA reduced acetylcholine-induced vasodilation; 50 microg/min acetylcholine increased forearm blood flow by 150+/-43% and 51+/-12% during saline and L-NMMA infusion, respectively (P<.01, n=6). In contrast, L-NMMA did not affect the increase in forearm blood flow produced by 3 microg/min nitroprusside (165+/-30% and 248+/-41% during saline and L-NMMA, respectively) or adenosine (173+/-48% and 270+/-75% during saline and L-NMMA, respectively). On the basis of our observations, we conclude that adenosine-induced vasodilation is not mediated by nitric oxide in the human forearm.

Effect of N-acetylcysteine on vascular endothelium function in aorta from oophorectomized rats.

PubMed

Delgado, J L; Landeras, J; Carbonell, L F; Parilla, J J; Abad, L; Quesada, T; Fiol, G; Hernández, I

1999-01-01

1. Experiments were performed to examine and to compare vascular endothelial function in aortic rings from oophorectomized and from ovary-intact rats and to test the effect of thiol compound as N-acetylcysteine on endothelial function. 2. In precontracted aortic rings from oophorectomized and intact rats, vascular endothelial function was evaluated by measuring changes in isometric force in response to cumulative doses of superoxide dismutase, acetylcholine and sodium nitroprusside. 3. In studies designed to assess the tone-related release of nitric oxide from aortic rings moderately precontracted with phenylephrine, superoxide dismutase produced a lower concentration-related relaxant response in aortic rings from oophorectomized rats than from ovary intact rats. 4. Acetylcholine caused a concentration- and endothelium-dependent relaxation of less magnitude in aortic rings from oophorectomized animals compared with those from ovary-intact rats. Addition of N-omega-nitro-L-arginine methyl ester eliminated the relaxation induced by both superoxide dismutase and acetylcholine. 5. No differences between groups were noticed in the concentration-relaxation curve induced by sodium nitroprusside. 6. Preincubation with N-acetylcysteine normalized the depressed vasorelaxant response to acetylcholine in the aortic rings from oophorectomized rats, whereas the concentration-response curve for acetylcholine in aortic rings from ovary-intact rats did not alter. 7. These results suggest that the absence of ovary estrogens is associated with a vascular endothelium dysfunction that can be reverted by addition of N-acetylcysteine, a thiol-containing compound with a free radical scavenger effect.

Differential actions of L-cysteine on responses to nitric oxide, nitroxyl anions and EDRF in the rat aorta

PubMed Central

Ellis, Anthie; Guang Li, Chun; Rand, Michael J

2000-01-01

The effects of L-cysteine were tested in rat aortic rings on responses to nitric oxide free radical (NO•), nitroxyl (NO−) derived from Angeli's salt and endothelium-derived relaxing factor (EDRF) activated by acetylcholine, ATP and the calcium ionophore A23187. Concentrations of 300 μM or less of L-cysteine had no effect on responses. Relaxations produced by exogenous NO• (0.25–2.5 μM) were markedly prolonged and relaxations produced by sodium nitroprusside (0.001–0.3 μM) were enhanced by 1 and 3 mM L-cysteine. The enhancements by L-cysteine of responses to NO• and sodium nitroprusside may be attributed to the formation of S-nitrosocysteine. Relaxations mediated by the nitroxyl anion (0.3 μM) donated from Angeli's salt were more prolonged than those produced by NO•, and nitroxyl-induced relaxations were reduced by L-cysteine (1 and 3 mM). EDRF-mediated relaxations produced by acetylcholine (0.01–10 μM), ATP (3–100 μM) and the calcium ionophore A23187 (0.1 μM) were significantly reduced by 3 mM L-cysteine. The similarity between the inhibitory effects of L-cysteine on responses to EDRF and on those to nitroxyl suggests that a component of the response to EDRF may be mediated by nitroxyl anion. PMID:10694238

Inhibition of nitric oxide synthesis in forearm vasculature of insulin-dependent diabetic patients: blunted vasoconstriction in patients with microalbuminuria.

PubMed

Elliott, T G; Cockcroft, J R; Groop, P H; Viberti, G C; Ritter, J M

1993-12-01

1. Microalbuminuria is a risk factor for cardiovascular disease in patients with insulin-dependent diabetes mellitus, and may be a marker of microvascular dysfunction including endothelial damage. The purpose of this study was to determine whether vasoconstrictor responses to NG-monomethyl-L-arginine, an inhibitor of endothelium-derived relaxing factor/nitric oxide biosynthesis, differ between healthy subjects and insulin-dependent patients with or without microalbuminuria. 2. Twenty-eight insulin-dependent diabetic patients (14 with normal albumin excretion, 14 with microalbuminuria) were studied under euglycaemic conditions, together with 14 healthy control subjects. Forearm vascular responses to brachial artery infusions of NG-monomethyl-L-arginine, sodium nitroprusside (an endothelium-independent nitrovasodilator) and carbachol (an endothelium-dependent vasodilator) were determined by strain gauge plethysmography. 3. Basal blood flow and vasodilator responses were similar in each group. NG-Monomethyl-L-arginine reduced blood flow by 41.3 +/- 2.3% (mean +/- SEM) in healthy control subjects, 34.0 +/- 3.4% in diabetic patients without microalbuminuria and 29.2 +/- 2.0% in diabetic patients with microalbuminuria. Diabetic patients differed from healthy subjects (P = 0.005), due to a difference between control subjects and microalbuminuric diabetic patients (P < 0.001). NG-Monomethyl-L-arginine did not influence nitroprusside responses but reduced carbachol responses in control subjects and normoalbuminuric diabetic patients but not in microalbuminuric diabetic patients. 4. These results provide evidence of abnormal endothelium-derived relaxing factor/nitric oxide biosynthesis in insulin-dependent diabetic patients with microalbuminuria.

Effect of load alterations on the effective regurgitant orifice area in chronic aortic regurgitation.

PubMed

Kim, Y J; Jones, M; Shiota, T; Tsujino, H; Qin, J X; Bauer, F; Sitges, M; Kwan, J; Cardon, L A; Zetts, A D; Thomas, J D

2002-10-01

To evaluate the load dependence of effective regurgitant orifice area (ROA) in an animal model of chronic aortic regurgitation. Eight sheep were studied 10-20 weeks after the surgical creation of aortic regurgitation. After baseline studies, 500 ml of blood, angiotensin II, and nitroprusside were infused sequentially. Electromagnetic flow meters were used as reference standards to determine aortic regurgitation volume. The time-velocity integral was acquired using the continuous wave Doppler method. Baseline aortic regurgitant volume varied from 8 ml (regurgitant fraction 28%) to 29 ml (59%), with a mean (SD) value of 17 (8) ml; mean ROA was 0.15 (0.05) cm2. During angiotensin II infusion, aortic regurgitation volume (20 (8) ml) and mean diastolic aortoventricular pressure gradient (62 (18) mm Hg) increased by 26 (16)% and 48 (64)%, respectively (p < 0.01 for both). ROA did not change (0.16 (0.06) cm(2), p = 0.15). During nitroprusside infusion, aortic regurgitant volume (13 (7) ml, p = 0.05) and diastolic pressure gradient (25 (13) mm Hg, p < 0.05) decreased. ROA did not change (0.15 (0.05) cm2). When analysing 32 stages together, aortic regurgitant volume (r = 0.78, p < 0.01) and regurgitant fraction (r = 0.55, p < 0.01) correlated well with ROA. However, diastolic pressure gradient (r = 0.28) was not significantly correlated with ROA. In an animal model of chronic aortic regurgitation, ROA did not change with load alterations.

Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats.

PubMed

Guerrero, Estela; Voces, Felipe; Ardanaz, Noelia; Montero, María José; Arévalo, Miguel; Sevilla, María Angeles

2003-09-01

The aim of this study was to assess the effects of long-term nebivolol therapy on high blood pressure, impaired endothelial function in aorta, and damage observed in heart and conductance arteries in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 9 weeks with nebivolol (8 mg/kg per day). Untreated SHR and Wistar Kyoto rats were used as hypertensive and normotensive controls, respectively. The left ventricle/body weight ratio was used as an index of cardiac hypertrophy, and to evaluate vascular function, responses induced by potassium chloride, noradrenaline, acetylcholine, and sodium nitroprusside were tested on aortic rings. Aortic morphometry and fibrosis were determined in parallel by a quantitative technique. Systolic blood pressure, measured by the tail-cuff method, was lower in treated SHR than in the untreated group (194 +/- 3 versus 150 +/- 4 mm Hg). The cardiac hypertrophy index was significantly reduced by the treatment. In aortic rings, treatment with nebivolol significantly reduced the maximal response to both KCl and NA in SHR. In vessels precontracted with phenylephrine relaxant, activity due to acetylcholine was higher in normotensive rats than in SHR and the treatment significantly improved this response. The effect of sodium nitroprusside on aortic rings was similar in all groups. Medial thickness and collagen content were significantly reduced in comparison with SHR. In conclusion, the chronic antihypertensive effect of nebivolol in SHR was accompanied by an improvement in vascular structure and function and in the cardiac hypertrophy index.

Acute and repeated exposure with the nitric oxide (NO) donor sodium nitroprusside (SNP) differentially modulate responses in a rat model of anxiety.

PubMed

Orfanidou, Martha A; Lafioniatis, Anastasios; Trevlopoulou, Aikaterini; Touzlatzi, Ntilara; Pitsikas, Nikolaos

2017-09-30

The nitric oxide (NO) donor sodium nitroprusside (SNP) actually is under investigation for the treatment of schizophrenia. That anxiety disorders are noted to occur commonly in schizophrenia patients is known. Contradictory results were reported however, concerning the effects of SNP in animal models of anxiety disorders. The present study investigated the effects of acute and repeated administration of SNP on anxiety-like behaviour in rats assessed in the light/dark test. The effects of SNP on motility in a locomotor activity chamber were also investigated in rats. Acute administration of 1 mg/kg SNP 30 but not 60 min before testing induced anxiolytic-like behaviour which cannot be attributed to changes in locomotor activity. Conversely, a single injection of 3 mg/kg SNP at 30 min before testing depressed rats' general activity, while at 60 min this dose did not influence performance of animals either in the light/dark or in the motor activity test. Repeated application of SNP (1 and 3 mg/kg, for 5 consecutive days) did not alter rodents' performance in the above described behavioural paradigms. The present results suggest that the effects exerted by SNP in the light/dark test in rats are dose, time and treatment schedule-dependent. The current findings propose also a narrow therapeutic window for SNP in this animal model of anxiety. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of different frequencies of transcutaneous electrical nerve stimulation on venous vascular reactivity

PubMed Central

Franco, O.S.; Paulitsch, F.S.; Pereira, A.P.C.; Teixeira, A.O.; Martins, C.N.; Silva, A.M.V.; Plentz, R.D.M.; Irigoyen, M.C.; Signori, L.U.

2014-01-01

Transcutaneous electrical nerve stimulation (TENS) is a type of therapy used primarily for analgesia, but also presents changes in the cardiovascular system responses; its effects are dependent upon application parameters. Alterations to the cardiovascular system suggest that TENS may modify venous vascular response. The objective of this study was to evaluate the effects of TENS at different frequencies (10 and 100 Hz) on venous vascular reactivity in healthy subjects. Twenty-nine healthy male volunteers were randomized into three groups: placebo (n=10), low-frequency TENS (10 Hz, n=9) and high-frequency TENS (100 Hz, n=10). TENS was applied for 30 min in the nervous plexus trajectory from the superior member (from cervical to dorsal region of the fist) at low (10 Hz/200 μs) and high frequency (100 Hz/200 μs) with its intensity adjusted below the motor threshold and intensified every 5 min, intending to avoid accommodation. Venous vascular reactivity in response to phenylephrine, acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) was assessed by the dorsal hand vein technique. The phenylephrine effective dose to achieve 70% vasoconstriction was reduced 53% (P<0.01) using low-frequency TENS (10 Hz), while in high-frequency stimulation (100 Hz), a 47% increased dose was needed (P<0.01). The endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) responses were not modified by TENS, which modifies venous responsiveness, and increases the low-frequency sensitivity of α1-adrenergic receptors and shows high-frequency opposite effects. These changes represent an important vascular effect caused by TENS with implications for hemodynamics, inflammation and analgesia. PMID:24820225

Influence of vehicle resistance on transdermal iontophoretic delivery of acetylcholine and sodium nitroprusside in humans.

PubMed

Khan, Faisel; Newton, David J; Smyth, Emily C; Belch, Jill J F

2004-09-01

Iontophoresis is a valuable method of noninvasive drug delivery for assessment of skin microvascular function, but it is important to consider and minimize its potential nonspecific electrical effects on blood flow. The use of sodium chloride (NaCl) instead of water as the iontophoresis vehicle has been reported to reduce these effects because it has a lower electrical resistance. However, this argument may not be valid when an agonist is added to the vehicle because its resistance will be changed. The aim of our study was to determine whether there is a difference in resistance between water and NaCl when used as vehicles for iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Four cumulative doses of each drug, dissolved in either water or NaCl, were delivered via iontophoresis to the forearm skin of 14 healthy volunteers. We measured the resulting blood flow responses by using laser-Doppler imaging and the voltage across the electrodes for each delivery as an index of resistance. For ACh and SNP, there were no significant differences between the voltages measured when either water or NaCl was used as the vehicle. However, the blood flow responses to both agonists were significantly lower with NaCl (ACh: 25% lower, P < 0.001; SNP: 15% lower, P = 0.019). The use of NaCl is therefore unlikely to decrease any nonspecific electrical effects, and it may in fact reduce the effective dose of drug delivered. Deionized water is a better iontophoresis vehicle for the assessment of microvascular function in skin when using ACh and SNP.

A selective spectrophotometric method for determination of rosoxacin antibiotic using sodium nitroprusside as a chromogenic reagent

NASA Astrophysics Data System (ADS)

Askal, Hassan F.; Refaat, Ibrahim H.; Darwish, Ibrahim A.; Marzouq, Mostafa A.

2008-04-01

A selective spectrophotometric method for the determination of rosoxacin (ROS), a 4-quinolone antimicrobial agent, has been developed and validated. The method was based on the reaction of ROS with alkaline sodium nitroprusside (SNP) reagent at room temperature forming a red colored chromogen measured at 455 nm. The conditions affecting the reaction (SNP concentration, pH, color-developing time, temperature, diluting solvent and chromogen stability time) were optimized. Under the optimum conditions, good linear relationship ( r = 0.9987) was obtained between the absorbance and the concentration of ROS in the range of 20-50 μg ml -1. The assay limits of detection and quantitation were 2.5 and 8.4 μg ml -1, respectively. The method was successfully applied to the analysis of bulk drug and laboratory-prepared tablets; the mean percentage recoveries were 100.1 ± 0.33 and 101.24 ± 1.28%, respectively. The results were compared favourably with those obtained by the reported method; no significant difference in the accuracy and precision as revealed by the accepted values of t- and F-tests, respectively. The robustness and ruggedness of the method was checked and satisfactory results were obtained. The proposed method was found to be highly selective for ROS among the fluoroquinolone antibiotics. The reaction mechanism was proposed and it proceeded in two steps; the formation of nitroferrocyanide by the action of sodium hydroxide alkalinity on SNP and the subsequent formation of the colored nitrosyl-ROS derivative by the attack at position 6 of ROS.

Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure

PubMed Central

Nath, Anjali K.; Roberts, Lee D.; Liu, Yan; Mahon, Sari B.; Kim, Sonia; Ryu, Justine H.; Werdich, Andreas; Januzzi, James L.; Boss, Gerry R.; Rockwood, Gary A.; MacRae, Calum A.; Brenner, Matthew; Gerszten, Robert E.; Peterson, Randall T.

2013-01-01

Exposure to cyanide causes a spectrum of cardiac, neurological, and metabolic dysfunctions that can be fatal. Improved cyanide antidotes are needed, but the ideal biological pathways to target are not known. To understand better the metabolic effects of cyanide and to discover novel cyanide antidotes, we developed a zebrafish model of cyanide exposure and scaled it for high-throughput chemical screening. In a screen of 3120 small molecules, we discovered 4 novel antidotes that block cyanide toxicity. The most potent antidote was riboflavin. Metabolomic profiling of cyanide-treated zebrafish revealed changes in bile acid and purine metabolism, most notably by an increase in inosine levels. Riboflavin normalizes many of the cyanide-induced neurological and metabolic perturbations in zebrafish. The metabolic effects of cyanide observed in zebrafish were conserved in a rabbit model of cyanide toxicity. Further, humans treated with nitroprusside, a drug that releases nitric oxide and cyanide ions, display increased circulating bile acids and inosine. In summary, riboflavin may be a novel treatment for cyanide toxicity and prophylactic measure during nitroprusside treatment, inosine may serve as a biomarker of cyanide exposure, and metabolites in the bile acid and purine metabolism pathways may shed light on the pathways critical to reversing cyanide toxicity.—Nath, A. K., Roberts, L. D., Liu, Y., Mahon, S. B., Kim, S., Ryu, J. H., Werdich, A., Januzzi, J. L., Boss, G. R., Rockwood, G. A., MacRae, C. A., Brenner, M., Gerszten, R. E., Peterson, R. T. Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure. PMID:23345455

MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside.

PubMed

Hurtubise, Jessica L; Marks, Wendie N; Davies, Don A; Catton, Jillian K; Baker, Glen B; Howland, John G

2017-01-01

The cognitive symptoms observed in schizophrenia are not consistently alleviated by conventional antipsychotics. Following a recent pilot study, sodium nitroprusside (SNP) has been identified as a promising adjunct treatment to reduce the working memory impairments experienced by schizophrenia patients. The present experiments were designed to explore the effects of SNP on the highly translatable trial-unique, delayed nonmatching-to-location (TUNL) task in rats with and without acute MK-801 treatment. SNP (0.5, 1.0, 2.0, 4.0, and 5.0 mg/kg) and MK-801 (0.05, 0.075, and 0.1 mg/kg) were acutely administered to rats trained on the TUNL task. Acute MK-801 treatment impaired TUNL task accuracy. Administration of SNP (2.0 mg/kg) with MK-801 (0.1 mg/kg) failed to rescue performance on TUNL. SNP (5.0 mg/kg) administration nearly 4 h prior to MK-801 (0.05 mg/kg) treatment had no preventative effect on performance impairments. SNP (2.0 mg/kg) improved performance on a subset of trials. These results suggest that SNP may possess intrinsic cognitive-enhancing properties but is unable to block the effects of acute MK-801 treatment on the TUNL task. These results are inconsistent with the effectiveness of SNP as an adjunct therapy for working memory impairments in schizophrenia patients. Future studies in rodents that assess SNP as an adjunct therapy will be valuable in understanding the mechanisms underlying the effectiveness of SNP as a treatment for schizophrenia.

Treatment Strategies for Paradoxical Hypertension Following Surgical Correction of Coarctation of the Aorta in Children

PubMed Central

Zwijsen, Eline G.

2017-01-01

Background: Paradoxical hypertension after repair of coarctation of the aorta is a well-known phenomenon. The pathogenesis involves the activation of the sympathetic nervous system (first phase) and renin–angiotensin system (second phase). Only a limited number of different treatment strategies have been published in the literature, without any comparative studies. Methods: Our aim was to describe the current international practice variation surrounding pharmacological treatment currently being employed to treat paradoxical hypertension following the repair of coarctation of the aorta in children. We performed an online survey among 197 members of the Pediatric Cardiac Intensive Care Society. We also conducted a systematic review of the literature regarding the treatment of paradoxical hypertension. Results: Eighty-eight people (45%), from 62 different centers, responded and answered the questions regarding blood pressure control. Nitroprusside is the first drug of choice for initial blood pressure control in 66% of respondents, esmolol in 11%, labetalol in 11%, and angiotensin-converting enzyme inhibitors (ACEIs) are used by 3% of respondents. For oral blood pressure control after discharge from the pediatric intensive care unit, 75% of respondents use ACEIs, 18% use labetalol, and 12% use other beta-blockers (propranolol, carvedilol, atenolol, metoprolol). The systematic review identified 14 articles reporting pharmacological treatment of direct postoperative hypertension following coarctation repair. Conclusion: There is wide practice variability, due to the lack of sufficient compelling evidence. The majority (66%) of caregivers use nitroprusside to control blood pressure in the acute postoperative phase. The ACEIs are the drug of choice for chronic blood pressure control. PMID:28520538

Role of aminophylline in refractory heart failure: a comparison to the vasodilator sodium nitroprusside, the old and the new.

PubMed

DiBianco, R; Rosenfeld, S P; Katz, R J; Simpson, A G; Fletcher, R D; Singh, S

1980-08-01

Aminophylline [(theophylline ethylene diamine (TED)] reportedly improved cardiac hemodynamics by lowering vascular resistances and increasing contractility. TED as used clinically has not been compared to the vasodilator sodium nitroprusside (NP). To assess the relative hemodynamic effects of these two commonly used agents, the following comparison was made. Ten patients with congestive cardiomyopathy in chronic refractory heart failure [New York Heart Association (NYHA) class IV] were studied. All patients demonstrated cardiomegaly by chest x ray and echocardiography (LVd = 6.3 +/- 0.7 cm) and markedly abnormal hemodynamics during baseline observations (see Table I). Hemodynamic measurements at baseline were compared after TED infusion (mean blood level = 16 +/- 12 micrograms/m/TED) and during intravenous NP. No significant changes in heart rate occurred during either therapeutic intervention; a fall in mean arterial pressure of 10 mmHg (p < 0.01) was observed during NP therapy; atrioventricular (AV) block with ventricular fibrillation was successfully treated in one patient after TED. Theophylline ethylene diamine demonstrated no detectable cardiac hemodynamic effects 60--90 min post infusion despite proven blood levels, whereas NP exhibited distinctly beneficial effects in this patient group. Previous studies demonstrating improved hemodynamics occurring with TED have been limited to the time of infusion or within the following 40 min, a time when TED blood levels are maximum and therefore closest to toxicity. The results of this study suggest that TED demonstrates no beneficial hemodynamic effects in refractory heart failure as early as 1 h after infusion despite blood levels in the therapeutic range.

Co-culture with human synovium-derived mesenchymal stem cells inhibits inflammatory activity and increases cell proliferation of sodium nitroprusside-stimulated chondrocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryu, Jae-Sung; Jung, Yeon-Hwa; Cho, Mi-Young

Highlights: • Co-culture of hSDMSCs with SNP-stimulated chondrocytes improves anti-inflammation. • Co-culture system produces IGF-1. • Co-culture system suppresses inflammatory genes expression. • Co-culture system improves cell proliferation. • Exogenous IGF-1 inhibits inflammatory activity in SNP-stimulated chondrocytes. - Abstract: Rheumatoid arthritis (RA) and osteoarthritis (OA) are primarily chronic inflammatory diseases. Mesenchymal stem cells (MSCs) have the ability to differentiate into cells of the mesodermal lineage, and to regulate immunomodulatory activity. Specifically, MSCs have been shown to secrete insulin-like growth factor 1 (IGF-1). The purpose of the present study was to examine the inhibitory effects on inflammatory activity from a co-culturemore » of human synovium-derived mesenchymal stem cells (hSDMSCs) and sodium nitroprusside (SNP)-stimulated chondrocytes. First, chondrocytes were treated with SNP to generate an in vitro model of RA or OA. Next, the co-culture of hSDMSCs with SNP-stimulated chondrocytes reduced inflammatory cytokine secretion, inhibited expression of inflammation activity-related genes, generated IGF-1 secretion, and increased the chondrocyte proliferation rate. To evaluate the effect of IGF-1 on inhibition of inflammation, chondrocytes pre-treated with IGF-1 were treated with SNP, and then the production of inflammatory cytokines was analyzed. Treatment with IGF-1 was shown to significantly reduce inflammatory cytokine secretion in SNP-stimulated chondrocytes. Our results suggest that hSDMSCs offer a new strategy to promote cell-based cartilage regeneration in RA or OA.« less

PGPR-mediated expression of salt tolerance gene in soybean through volatiles under sodium nitroprusside.

PubMed

Vaishnav, Anukool; Kumari, Sarita; Jain, Shekhar; Varma, Ajit; Tuteja, Narendra; Choudhary, Devendra Kumar

2016-11-01

Increasing evidence shows that nitric oxide (NO), a typical signaling molecule plays important role in development of plant and in bacteria-plant interaction. In the present study, we tested the effect of sodium nitroprusside (SNP)-a nitric oxide donor, on bacterial metabolism and its role in establishment of PGPR-plant interaction under salinity condition. In the present study, we adopted methods namely, biofilm formation assay, GC-MS analysis of bacterial volatiles, chemotaxis assay of root exudates (REs), measurement of electrolyte leakage and lipid peroxidation, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for gene expression. GC-MS analysis revealed that three new volatile organic compounds (VOCs) were expressed after treatment with SNP. Two VOCs namely, 4-nitroguaiacol and quinoline were found to promote soybean seed germination under 100 mM NaCl stress. Chemotaxis assay revealed that SNP treatment, altered root exudates profiling (SS-RE), found more attracted to Pseudomonas simiae bacterial cells as compared to non-treated root exudates (S-RE) under salt stress. Expression of Peroxidase (POX), catalase (CAT), vegetative storage protein (VSP), and nitrite reductase (NR) genes were up-regulated in T6 treatment seedlings, whereas, high affinity K + transporter (HKT1), lipoxygenase (LOX), polyphenol oxidase (PPO), and pyrroline-5-carboxylate synthase (P5CS) genes were down-regulated under salt stress. The findings suggest that NO improves the efficiency and establishment of PGPR strain in the plant environment during salt condition. This strategy may be applied on soybean plants to increase their growth during salinity stress. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The nitric oxide donor sodium nitroprusside attenuates recognition memory deficits and social withdrawal produced by the NMDA receptor antagonist ketamine and induces anxiolytic-like behaviour in rats.

PubMed

Trevlopoulou, Aikaterini; Touzlatzi, Ntilara; Pitsikas, Nikolaos

2016-03-01

Experimental evidence indicates that the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine impairs cognition and can mimic certain aspects of positive and negative symptoms of schizophrenia in rodents. Nitric oxide (NO) is considered as an intracellular messenger in the brain, and its abnormalities have been linked to schizophrenia. The present study was designed to investigate the ability of the NO donor sodium nitroprusside (SNP) to counteract schizophrenia-like behavioural deficits produced by ketamine in rats. The ability of SNP to reverse ketamine-induced memory deficits and social withdrawal were assessed using the novel object recognition task (NORT) and the social interaction test, respectively. Furthermore, since anxiety disorders are noted to occur commonly in schizophrenics, the effects of SNP on anxiety-like behaviour were examined using the light/dark test. Locomotor activity was also assessed as an independent measure of the potential motoric effects of this NO donor. SNP (0.3 and 1 mg/kg) reversed ketamine (3 mg/kg)-induced short-term recognition memory deficits. SNP (1 mg/kg) counteracted the ketamine (8 mg/kg)-induced social isolation in the social interaction test. The anxiolytic-like effects in the light/dark test of SNP (1 mg/kg) cannot be attributed to changes in locomotor activity. Our findings illustrate a functional interaction between the nitrergic and glutamatergic system that may be of relevance for schizophrenia-like behavioural deficits. The data also suggest a role of NO in anxiety.

Perioperative Management of Severe Hypertension during Laparoscopic Surgery for Pheochromocytoma

PubMed Central

Erdoğan, Mehmet Ali; Uçar, Muharrem; Özkan, Ahmet Selim; Özgül, Ülkü; Durmuş, Mahmut

2016-01-01

Phaeochromocytoma is a catecholamine-secreting vascular tumour that is derived from chromaffin cell. Lethal cardiovascular complications, such as serious hypertension, myocardial infarction and aortic dissection, may occur because of uncontrolled catecholamine release. Each stage of anaesthesia management has vital importance because of this destructive catecholamine secretion that may occur during induction, perioperative stage and surgical manipulation. In this study, we report regarding the preoperative preparation and severe, persistent hypertension attack management with a combination of α-adrenergic blockade, β-adrenergic blockade, sodium nitroprusside and remifentanil in a patient who underwent laparoscopic surgery for phaeochromocytoma. PMID:27366556

Effects of nitric oxide synthase inhibition on sympathetically-mediated tachycardia

NASA Technical Reports Server (NTRS)

Whalen, E. J.; Johnson, A. K.; Lewis, S. J.

1999-01-01

The aim of the present study was to determine whether inhibition of nitric oxide (NO) synthesis directly alters the tachycardia produced by sympathetically-derived norepinephrine. The NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 50 micromol/kg, i.v.), produced a marked rise in mean arterial blood pressure. This pressor response was associated with a fall in heart rate which involved the withdrawal of cardiac sympathetic nerve activity. The NO-donor, sodium nitroprusside (5 microg/kg, i.v.), produced a pronounced fall in mean arterial blood pressure but only a minor increase in heart rate. The beta-adrenoceptor agonist, isoproterenol (0.5 micromol/kg, i.v.), and the membrane-permeable cAMP analogue, 8-(4-chlorophenylthiol)-cAMP (10 micromol/kg, i.v.), produced falls in mean arterial blood pressure and pronounced increases in heart rate. The indirectly acting sympathomimetic agent, tyramine (0.5 mg/kg, i.v.), produced a pressor response and a tachycardia. The effects of sodium nitroprusside, tyramine, isoproterenol and 8-(4-chlorophenylthiol)-cAMP on mean arterial blood pressure were not markedly affected by L-NAME. However, the tachycardia produced by these agents was considerably exaggerated in the presence of this NO synthesis inhibitor. These findings suggest that L-NAME potentiates the tachycardia produced by sympathetically-derived norepinephrine. The increased responsiveness to norepinephrine may involve (i) a rapid up-regulation of cardiac beta1-adrenoceptors and cAMP signaling in cardiac pacemaker cells due to the loss of the inhibitory influence of cardiac NO, and (ii) the up-regulation of beta1-adrenoceptor-mediated signal transduction processes in response to the L-NAME-induced withdrawal of cardiac sympathetic nerve activity.

Predictors of Arterial Blood Pressure Control During Deliberate Hypotension with Sodium Nitroprusside in Children

PubMed Central

Spielberg, David R; Barrett, Jeffrey S; Hammer, Gregory B; Drover, David R; Reece, Tammy; Cohane, Carol A; Schulman, Scott R

2014-01-01

Background Sodium nitroprusside (SNP) is used to decrease arterial blood pressure (BP) during certain surgical procedures. There are limited data regarding efficacy of BP control with SNP. There are no data on patient and clinician factors that affect BP control. We evaluated the dose-response relationship of SNP in infants and children undergoing major surgery and performed a quantitative assessment of BP control. Methods One hundred fifty-three subjects at 7 sites received a blinded infusion followed by open-label SNP during operative procedures requiring controlled hypotension. SNP was administered by continuous infusion and titrated to maintain BP control (mean arterial BP [MAP] within ±10% of clinician-defined target). BP was recorded using an arterial catheter. Statistical Process Control methodology was used to quantify BP control. A multivariable model assessed the effects of patient and procedural factors. Results BP was controlled an average 45.4% (SD 23.9%, 95% CI 41.5%-49.18%) of the time. Larger changes in infusion rate were associated with worse BP control (7.99% less control for 1 mcg•kg−•min− increase in average titration size, p=0.0009). A larger difference between a patient's baseline and target MAP predicted worse BP control (0.93% worse control per 1 mmHg increase in MAP difference, p=0.0013). Both effects persisted in multivariable models. Conclusions : SNP was effective in reducing BP. However, BP was within the target range less than half of the time. No clinician or patient factors were predictive of BP control, although two inverse relationships were identified. These relationships require additional study and may be best coupled with exposure-response modeling to propose improved dosing strategies when using SNP for controlled hypotension in the pediatric population. PMID:25099924

Beneficial Effects of Apelin on Vascular Function in Patients With Central Obesity.

PubMed

Schinzari, Francesca; Veneziani, Augusto; Mores, Nadia; Barini, Angela; Di Daniele, Nicola; Cardillo, Carmine; Tesauro, Manfredi

2017-05-01

Patients with central obesity have impaired insulin-stimulated vasodilation and increased ET-1 (endothelin 1) vasoconstriction, which may contribute to insulin resistance and vascular damage. Apelin enhances insulin sensitivity and glucose disposal but also acts as a nitric oxide (NO)-dependent vasodilator and a counter-regulator of AT 1 (angiotensin [Ang] II type 1) receptor-induced vasoconstriction. We, therefore, examined the effects of exogenous (Pyr 1 )apelin on NO-mediated vasodilation and Ang II- or ET-1-dependent vasoconstrictor tone in obese patients. In the absence of hyperinsulinemia, forearm blood flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during saline or apelin administration (both P >0.05). During intra-arterial infusion of regular insulin, however, apelin enhanced the vasodilation induced by both acetylcholine and nitroprusside (both P <0.05). Interestingly, the vasodilator effect of concurrent blockade of AT 1 (telmisartan) and AT 2 (PD 123,319) receptors was blunted by apelin (3±5% versus 32±9%; P <0.05). Similarly, during apelin administration, blockade of ET A receptors (BQ-123) resulted in lower vasodilator response than during saline (23±10% versus 65±12%; P <0.05). NO synthase inhibition by L-NMMA (l- N -monometylarginine) during the concurrent blockade of either Ang II or ET A receptors resulted in similar vasoconstriction in the absence or presence of apelin ( P >0.05). In conclusion, in patients with central obesity, apelin has favorable effects not only to improve insulin-stimulated endothelium-dependent and endothelium-independent vasodilator responses but also to blunt Ang II- and ET-1-dependent vasoconstriction by a mechanism not involving NO. Taken together, our results suggest that targeting the apelin system might favorably impact some hemodynamic abnormalities of insulin-resistant states like obesity. © 2017 American Heart Association, Inc.

Developmental stage- and concentration-specific sodium nitroprusside application results in nitrate reductase regulation and the modification of nitrate metabolism in leaves of Medicago truncatula plants

PubMed Central

Antoniou, Chrystalla; Filippou, Panagiota; Mylona, Photini; Fasoula, Dionysia; Ioannides, Ioannis; Polidoros, Alexios; Fotopoulos, Vasileios

2013-01-01

Nitric oxide (NO) is a bioactive molecule involved in numerous biological events that has been reported to display both pro-oxidant and antioxidant properties in plants. Several reports exist which demonstrate the protective action of sodium nitroprusside (SNP), a widely used NO donor, which acts as a signal molecule in plants responsible for the expression regulation of many antioxidant enzymes. This study attempts to provide a novel insight into the effect of application of low (100 μΜ) and high (2.5 mM) concentrations of SNP on the nitrosative status and nitrate metabolism of mature (40 d) and senescing (65 d) Medicago truncatula plants. Higher concentrations of SNP resulted in increased NO content, cellular damage levels and reactive oxygen species (ROS) concentration, further induced in older tissues. Senescing M. truncatula plants demonstrated greater sensitivity to SNP-induced oxidative and nitrosative damage, suggesting a developmental stage-dependent suppression in the plant’s capacity to cope with free oxygen and nitrogen radicals. In addition, measurements of the activity of nitrate reductase (NR), a key enzyme involved in the generation of NO in plants, indicated a differential regulation in a dose and time-dependent manner. Furthermore, expression levels of NO-responsive genes (NR, nitrate/nitrite transporters) involved in nitrogen assimilation and NO production revealed significant induction of NR and nitrate transporter during long-term 2.5 mM SNP application in mature plants and overall gene suppression in senescing plants, supporting the differential nitrosative response of M. truncatula plants treated with different concentrations of SNP. PMID:23838961

Metabolic activation of sodium nitroprusside to nitric oxide in vascular smooth muscle.

PubMed

Kowaluk, E A; Seth, P; Fung, H L

1992-09-01

Sodium nitroprusside (SNP) is thought to exert its vasodilating activity, at least in part, by vascular activation to nitric oxide (NO), but the activation mechanism has not been delineated. This study has examined the potential for vascular metabolism of SNP to NO in bovine coronary arterial smooth muscle subcellular fractions using a sensitive and specific redox-chemiluminescence assay for NO. SNP was readily metabolized to NO in subcellular fractions, and the dominant site of metabolism appeared to be located in the membrane fractions. NO-generating activity was significantly enhanced by, but did not absolutely require, the addition of a NADPH-regenerating system, NADPH per se, NADH or cysteine. A correlation analysis of NO-generating activity (in the presence of a NADPH-regenerating system) with marker enzyme activities indicated that the SNP-directed NO-generating activity was primarily membrane-associated. Radiation inactivation target-size analysis revealed that the microsomal SNP-directed NO-generating activity was relatively insensitive to inactivation by radiation exposure, suggesting that the functioning catalytic unit might be quite small. A molecular weight of 5 to 11 kDa was estimated. NO-generating activity could be solubilized from the crude microsomes with 3-[(3-cholamidopropyl)- dimethylammonio]-1-propane sulfonate, and the solubilized extract was subjected to gel filtration chromatography. NO-generating activity was eluted in two peaks: one peak corresponding to an approximate molecular weight of 4 kDa, thus confirming the existence of a small molecular weight NO-generating activity, and a second activity peak corresponding to a molecular weight of 112 to 169 kDa, the functional significance of which is unclear at present.(ABSTRACT TRUNCATED AT 250 WORDS)

The NO donor sodium nitroprusside: evaluation of skeletal muscle vascular and metabolic dysfunction

PubMed Central

Hirai, Daniel M.; Copp, Steven W.; Ferguson, Scott K.; Holdsworth, Clark T.; Musch, Timothy I.; Poole, David C.

2012-01-01

The nitric oxide (NO) donor sodium nitroprusside (SNP) may promote cyanide-induced toxicity and systemic and/or local responses approaching maximal vasodilation. The hypotheses were tested that SNP superfusion of the rat spinotrapezius muscle exerts 1) residual impairments in resting and contracting blood flow, oxygen utilization (V̇O2) and microvascular O2 pressure (PO2mv); and 2) marked hypotension and elevation in resting PO2mv. Two superfusion protocols were performed: 1) Krebs-Henseleit (control 1), SNP (300 µM; a dose used commonly in superfusion studies) and Krebs-Henseleit (control 2), in this order; 2) 300 and 1200 µM SNP in random order. Spinotrapezius muscle blood flow (radiolabeled microspheres), V̇O2 (Fick calculation) and PO2mv (phosphorescence quenching) were determined at rest and during electrically-induced (1 Hz) contractions. There were no differences in spinotrapezius blood flow, V̇O2 or PO2mv at rest and during contractions pre- and post-SNP condition (control 1 and control 2; p>0.05 for all). With regard to dosing, SNP produced a graded elevation in resting PO2mv (p<0.05) with a reduction in mean arterial pressure only at the higher concentration (p<0.05). Contrary to our hypothesis, skeletal muscle superfusion with the NO donor SNP (300 µM) improved microvascular oxygenation during the transition from rest to contractions (PO2mv kinetics) without precipitating residual impairment of muscle hemodynamic or metabolic control or compromising systemic hemodynamics. These data suggest that SNP superfusion (300 µM) constitutes a valid and important tool for assessing the functional roles of NO in resting and contracting skeletal muscle function without incurring residual alterations consistent with cyanide accumulation and poisoning. PMID:23174313

Quercetin and pioglitazone synergistically reverse endothelial dysfunction in isolated aorta from fructose-streptozotocin (F-STZ)-induced diabetic rats.

PubMed

Kunasegaran, Thubasni; Mustafa, Mohd Rais; Achike, Francis I; Murugan, Dharmani Devi

2017-03-15

Pioglitazone is an anti-diabetic drug with potential to cause adverse effects following prolonged use. This study, therefore, investigated the effects of combination treatment of a subliminal concentration of pioglitazone and quercetin, a potent antioxidant, on vascular reactivity of aorta isolated from fructose-streptozotocin (F-STZ)-induced diabetic rats. Relaxation to acetylcholine and sodium nitroprusside, and contraction to phenylephrine were tested in organ bath chambers following pre-incubation with vehicle (DMSO; 0.05%), quercetin (10-7 M), pioglitazone (10-7 M), or their combination (P+Q; 10-7 M each drug). Subliminal concentration of quercetin or pioglitazone did not alter the acetylcholine- induced relaxation nor the phenylephrine-induced contraction in both normal rat and diabetic F-STZ induced tissues. However, P+Q combination synergistically improved the impaired acetylcholine-induced relaxation and decreased the elevated phenylephrine-induced contraction in aortic rings from diabetic, but not in the normal rats. Neither mono nor combination treatment altered sodium nitroprusside-induced relaxation. The combination also synergistically decreased superoxide anion and increased nitric oxide production compared to the individual treatments in aorta from diabetic rats. Overall, these data demonstrated a synergistic effect, in which, a combination (P+Q; 10-7 M each drug) caused a significantly greater effect than 10-6 M of either agent in improving endothelial function of isolated diabetic aorta. In conclusion, a combination of subliminal concentrations of pioglitazone and quercetin is able to decrease oxidative stress and provide synergistic vascular protection in type 2 diabetes mellitus and thus the possibility of using quercetin as a supplement to pioglitazone in the treatment of diabetes with the goal of reducing pioglitazone toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of perioperative blood pressure variability on health resource utilization after cardiac surgery: an analysis of the ECLIPSE trials.

PubMed

Aronson, Solomon; Levy, Jerrold H; Lumb, Philip D; Fontes, Manuel; Wang, Yamei; Crothers, Tracy A; Sulham, Katherine A; Navetta, Marco S

2014-06-01

To examine the impact of blood pressure control on hospital health resource utilization using data from the ECLIPSE trials. Post-hoc analysis of data from 3 prospective, open-label, randomized clinical trials (ECLIPSE trials). Sixty-one medical centers in the United States. Patients 18 years or older undergoing cardiac surgery. Clevidipine was compared with nitroglycerin, sodium nitroprusside, and nicardipine. The ECLIPSE trials included 3 individual randomized open-label studies comparing clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine. Blood pressure control was assessed as the integral of the cumulative area under the curve (AUC) outside specified systolic blood pressure ranges, such that lower AUC represents less variability. This analysis examined surgery duration, time to extubation, as well as intensive care unit (ICU) and hospital length of stay (LOS) in patients with AUC≤10 mmHg×min/h compared to patients with AUC>10 mmHg×min/h. One thousand four hundred ten patients were included for analysis; 736 patients (52%) had an AUC≤10 mmHg×min/h, and 674 (48%) had an AUC>10 mmHg×min/h. The duration of surgery and ICU LOS were similar between groups. Time to extubation and postoperative LOS were both significantly shorter (p = 0.05 and p<0.0001, respectively) in patients with AUC≤10. Multivariate analysis demonstrates AUC≤10 was significantly and independently associated with decreased time to extubation (hazard ratio 1.132, p = 0.0261) and postoperative LOS (hazard ratio 1.221, p = 0.0006). Based on data derived from the ECLIPSE studies, increased perioperative BP variability is associated with delayed time to extubation and increased postoperative LOS. Copyright © 2014 Elsevier Inc. All rights reserved.

Predictors of arterial blood pressure control during deliberate hypotension with sodium nitroprusside in children.

PubMed

Spielberg, David R; Barrett, Jeffrey S; Hammer, Gregory B; Drover, David R; Reece, Tammy; Cohane, Carol A; Schulman, Scott R

2014-10-01

Sodium nitroprusside (SNP) is used to decrease arterial blood pressure (BP) during certain surgical procedures. There are limited data regarding efficacy of BP control with SNP. There are no data on patient and clinician factors that affect BP control. We evaluated the dose-response relationship of SNP in infants and children undergoing major surgery and performed a quantitative assessment of BP control. One hundred fifty-three subjects at 7 sites received a blinded infusion followed by open-label SNP during operative procedures requiring controlled hypotension. SNP was administered by continuous infusion and titrated to maintain BP control (mean arterial BP [MAP] within ±10% of clinician-defined target). BP was recorded using an arterial catheter. Statistical process control methodology was used to quantify BP control. A multivariable model assessed the effects of patient and procedural factors. BP was controlled an average 45.4% (SD 23.9%; 95% CI, 41.5%-49.18%) of the time. Larger changes in infusion rate were associated with worse BP control (7.99% less control for 1 μg·kg·min increase in average titration size, P = 0.0009). A larger difference between a patient's baseline and target MAP predicted worse BP control (0.93% worse control per 1-mm Hg increase in MAP difference, P = 0.0013). Both effects persisted in multivariable models. SNP was effective in reducing BP. However, BP was within the target range less than half of the time. No clinician or patient factors were predictive of BP control, although 2 inverse relationships were identified. These relationships require additional study and may be best coupled with exposure-response modeling to propose improved dosing strategies when using SNP for controlled hypotension in the pediatric population.

Hydrothermal recrystallization of transition metal nitroprussides. Formation of the most stable phases

NASA Astrophysics Data System (ADS)

Echevarría, F.; Reguera, L.; González M, M.; Galicia, J.; Ávila, M.; Reguera, E.

2018-02-01

Hydrothermal recrystallization appears to be an appropriate treatment to explore the structural diversity of porous coordination polymers. In this contribution, such a post-synthesis treatment is applied to divalent transition metal nitroprussides, T[Fe(CN)5NO]•xH2O with T =Mn, Fe, Co, Ni, Cu, Zn, Cd. This family of compounds forms an interesting series of nanoporous coordination polymers with a wide structural diversity, related to the synthesis route used and the solid hydration degree (x). The effect of a hydrothermal recrystallization of previously prepared fine powders using the precipitation method, on their crystal structure and related properties is herein discussed. In this series of coordination polymers, for Fe, Co, Ni the precipitated powders are obtained as cubic phase, with a high porosity related to presence of systematic vacancies for building unit [Fe(CN)5NO]. For Fe and Co a structural transition, from cubic to orthorhombic, was observed, which is associated to formation of a most compact structure. The crystal structure for the new orthorhombic phases was refined from the collected powder HR-XRD patterns. For Ni, the cubic phase remains stable even for large heating time, which is ascribed to the high polarizing power of this metal. The high porosity for the cubic phase allows an easy accommodation for the local deformations around the Ni atom coordination sphere. The structural information from XRD was complemented with CO2 and H2 adsorption and TG data, IR and UV-vis spectra, and magnetic measurements. The magnetic data, through the presence of spin-orbit coupling for Fe and Co in the two phases, provide fine details on the coordination environment for the metal linked at the N ends of the CN group.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teicher, B.A.; Holden, S.A.; Northey, D.

The perfluorochemical emulsion Fluosol-DA plus carbogen breathing has been shown to increase the effectiveness of radiation therapy in preclinical solid tumors when the emulsion was administered by i.v. bolus injection. Much of the enhancement in tumor radiation response was lost when the emulsion was administered slowly. The authors hypothesized that an increase in tumor perfusion resulted when Fluosol-DA was administered rapidly. In the present study, the [alpha]/[beta] agonist ephedrine, the Ca[sup 2+] channel blocker flunarizine and the nitric oxide producing vasodilating drug nitroprusside have been tested. Ephedrine administration resulted in a decrease in the radiation plus Fluosol-DA [+-] carbogen antitumormore » effects in both the Lewis lung carcinoma and FSaIIC tumor systems. In contrast, flunarizine administration resulted in an increase in the efficacy of the radiation plus carbogen and the radiation plus Fluosol-DA/carbogen in both emulsion was given rapidly. Even with flunarizine administration Fluosol-DA delivered slowly was less effective than when the emulsion was given rapidly. Flunarizine with Fluosol-DA infused i.v. over 30 min followed by carbogen breathing prior to and during radiation therapy resulted in a 1.7-1.6-fold increase in response compared with 2.4-2.2-fold with Fluosol-DA administered by injection i.v. and carbogen breathing prior to and during radiation therapy using growth delay of the Lewis lung carcinoma. The effects of nitroprusside were complex. This drug had considerably more effect at 10 Gy than at higher radiation doses. These studies suggest that Fluosol-DA given by i.v. injection may increase tumor perfusion and that a drug like flunarizine may be beneficial if the Fluosol-DA is administered slowly followed by carbogen breathing and radiation therapy. 45 refs., 4 figs.« less

Neuroprotective and anti-apoptotic propensity of Bacopa monniera extract against sodium nitroprusside induced activation of iNOS, heat shock proteins and apoptotic markers in PC12 cells.

PubMed

Pandareesh, M D; Anand, T

2014-05-01

Sodium nitroprusside (SNP) is a widely used nitric oxide (NO) donor, known to exert nitrative stress by up-regulation of inducible nitric oxide synthase (iNOS). Nω-nitro-L-arginine-methyl esther (L-NAME) is a NO inhibitor, which inhibits iNOS expression, is used as positive control. The present study was designed to assess neuroprotective propensity of Bacopa monniera extract (BME) in SNP-induced neuronal damage and oxido-nitrative stress in PC12 cells via modulation of iNOS, heat shock proteins and apoptotic markers. Our results elucidate that pre-treatment of PC12 cells with BME ameliorates the mitochondrial and plasma membrane damage induced by SNP (200 μM) as evidenced by MTT and LDH assays. BME pre-treatment inhibited NO generation by down regulating iNOS expression. BME replenished the depleted antioxidant status induced by SNP treatment. SNP-induced damage to cellular, nuclear and mitochondrial integrity was also restored by BME, which was confirmed by ROS estimation, comet assay and mitochondrial membrane potential assays respectively. BME pre-treatment efficiently attenuated the SNP-induced apoptotic protein biomarkers such as Bax, Bcl-2, cytochrome-c and caspase-3, which orchestrate the proteolytic damage of the cell. Q-PCR results further elucidated up-regulation of neuronal cell stress markers like HO-1 and iNOS and down-regulation of BDNF upon SNP exposure was attenuated by BME pre-treatment. By considering all these findings, we report that BME protects PC12 cells against SNP-induced toxicity via its free radical scavenging and neuroprotective mechanism.

Continuous positive airway pressure improves vascular function in obstructive sleep apnoea/hypopnoea syndrome: a randomised controlled trial.

PubMed

Cross, M D; Mills, N L; Al-Abri, M; Riha, R; Vennelle, M; Mackay, T W; Newby, D E; Douglas, N J

2008-07-01

The obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is associated with hypertension and increased cardiovascular risk, particularly when accompanied by marked nocturnal hypoxaemia. The mechanisms of these associations are unclear. We hypothesised that OSAHS combined with severe nocturnal hypoxaemia causes impaired vascular function that can be reversed by continuous positive airways pressure (CPAP) therapy. We compared vascular function in two groups of patients with OSAHS: 27 with more than 20 4% desaturations/h (desaturator group) and 19 with no 4% and less than five 3% desaturations/h (non-desaturator group). In a randomised, double blind, placebo controlled, crossover trial, the effect of 6 weeks of CPAP therapy on vascular function was determined in the desaturator group. In all studies, vascular function was assessed invasively by forearm venous occlusion plethysmography during intra-arterial infusion of endothelium dependent (acetylcholine 5-20 microg/min and substance P 2-8 pmol/min) and independent (sodium nitroprusside 2-8 microg/min) vasodilators. Compared with the non-desaturator group, patients with OSAHS and desaturations had reduced vasodilatation to all agonists (p = 0.007 for all). The apnoea/hypopnoea index and desaturation frequency were inversely related to peak vasodilatation with acetylcholine (r = -0.44, p = 0.002 and r = -0.43, p = 0.003) and sodium nitroprusside (r = -0.42, p = 0.009 and r = -0.37, p = 0.02). In comparison with placebo, CPAP therapy improved forearm blood flow to all vasodilators (p = 0.01). Patients with OSAHS and frequent nocturnal desaturations have impaired endothelial dependent and endothelial independent vasodilatation that is proportional to hypoxaemia and is improved by CPAP therapy. Impaired vascular function establishes an underlying mechanism for the adverse cardiovascular consequences of OSAHS.

Chronic stimulation of farnesoid X receptor impairs nitric oxide sensitivity of vascular smooth muscle.

PubMed

Kida, Taiki; Murata, Takahisa; Hori, Masatoshi; Ozaki, Hiroshi

2009-01-01

Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily that is highly expressed in enterohepatic tissue, is implicated in bile acid, lipid, and glucose metabolisms. Although recent studies showed that FXR is also expressed in vascular endothelial cells and smooth muscle cells, its physiological and/or pathological roles in vasculature tissue remain unknown. The aim of this study is to examine the chronic effect of synthetic FXR agonist GW4064 on vascular contraction and endothelium-dependent relaxation using tissue culture procedure. In cultured rabbit mesenteric arteries, the treatment with 0.1-10 microM GW4064 for 7 days did not influence vascular contractility induced by high K(+) (15-65 mM), norepinephrine (0.1-100 microM), and endothelin-1 (0.1-100 nM). However, the chronic treatment with GW4064 (1-10 microM for 7 days) dose dependently impaired endothelium-dependent relaxation induced by substance P (0.1-30 nM). In hematoxylin-eosin cross sectioning and en face immunostaining, GW4064 had no effects on the morphology of endothelial and smooth muscle cells. In endothelium-denuded arteries treated with GW4064 (1-10 microM) for 7 days, 3 nM-100 microM sodium nitroprusside-induced vasorelaxation, but not membrane-permeable cGMP analog 8-bromoguanosine-cGMP (8-Br-cGMP; 1-100 microM)-induced vasorelaxation, was significantly impaired. In these GW4064-treated arteries, 1 muM sodium nitroprusside-induced intracellular cGMP elevations were impaired. In RT-PCR, any changes were detected in mRNA expression level of alpha(1)- and beta(1)-subunit of soluble guanylyl cyclase. These results suggest that chronic stimulation of FXR impairs endothelium-dependent relaxation, which is due to decreased sensitivity of smooth muscle cells to nitric oxide.

Structural and functional changes in the microcirculation of lepromatous leprosy patients - Observation using orthogonal polarization spectral imaging and laser Doppler flowmetry iontophoresis

PubMed Central

Treu, Curt; de Souza, Maria das Graças Coelho; Lupi, Omar; Sicuro, Fernando Lencastre; Maranhão, Priscila Alves; Kraemer-Aguiar, Luiz Guilherme; Bouskela, Eliete

2017-01-01

Leprosy is a chronic granulomatous infection of skin and peripheral nerves caused by Mycobacterium leprae and is considered the main infectious cause of disability worldwide. Despite the several studies regarding leprosy, little is known about its effects on microvascular structure and function in vivo. Thus, we have aimed to compare skin capillary structure and functional density, cutaneous vasomotion (spontaneous oscillations of arteriolar diameter), which ensures optimal blood flow distribution to skin capillaries) and cutaneous microvascular blood flow and reactivity between ten men with lepromatous leprosy (without any other comorbidity) and ten age- and gender-matched healthy controls. Orthogonal polarization spectral imaging was used to evaluate skin capillary morphology and functional density and laser Doppler flowmetry to evaluate blood flow, vasomotion and spectral analysis of flowmotion (oscillations of blood flow generated by vasomotion) and microvascular reactivity, in response to iontophoresis of acetylcholine and sodium nitroprusside. The contribution of different frequency components of flowmotion (endothelial, neurogenic, myogenic, respiratory and cardiac) was not statistically different between groups. However, endothelial-dependent and -independent vasodilatations elicited by acetylcholine and sodium nitroprusside iontophoresis, respectively, were significantly reduced in lepromatous leprosy patients compared to controls, characterizing the existence of microvascular dysfunction. These patients also presented a significant increase in the number of capillaries with morphological abnormalities and in the diameters of the dermal papilla and capillary bulk when compared to controls. Our results suggest that lepromatous leprosy causes severe microvascular dysfunction and significant alterations in capillary structure. These structural and functional changes are probably induced by exposure of the microvascular bed to chronic inflammation evoked by the Mycobacterium leprae. PMID:28419120

Mechanisms underlying sodium nitroprusside-induced tolerance in the mouse aorta: Role of ROS and cyclooxygenase-derived prostanoids.

PubMed

Diniz, Mariana C; Olivon, Vania C; Tavares, Lívia D; Simplicio, Janaina A; Gonzaga, Natália A; de Souza, Daniele G; Bendhack, Lusiane M; Tirapelli, Carlos R; Bonaventura, Daniella

2017-05-01

To determine the role of reactive oxygen species (ROS) on sodium nitroprusside (SNP)-induced tolerance. Additionally, we evaluated the role of ROS on NF-κB activation and pro-inflammatory cytokines production during SNP-induced tolerance. To induce in vitro tolerance, endothelium-intact or -denuded aortic rings isolated from male Balb-c mice were incubated for 15, 30, 45 or 60min with SNP (10nmol/L). Tolerance to SNP was observed after incubation of endothelium-denuded, but not endothelium-intact aortas for 60min with this inorganic nitrate. Pre-incubation of denuded rings with tiron (superoxide anion (O 2 - ) scavenger), and the NADPH oxidase inhibitors apocynin and atorvastatin reversed SNP-induced tolerance. l-NAME (non-selective NOS inhibitor) and l-arginine (NOS substrate) also prevented SNP-induced tolerance. Similarly, ibuprofen (non-selective cyclooxygenase (COX) inhibitor), nimesulide (selective COX-2 inhibitor), AH6809 (prostaglandin PGF 2 α receptor antagonist) or SQ29584 [PGH 2 /thromboxane TXA 2 receptor antagonist] reversed SNP-induced tolerance. Increased ROS generation was detected in tolerant arteries and both tiron and atorvastatin reversed this response. Tiron prevented tolerance-induced increase on O 2 - and hydrogen peroxide (H 2 O 2 ) levels. The increase onp65/NF-κB expression and TNF-α production in tolerant arteries was prevented by tiron. The major new finding of our study is that SNP-induced tolerance is mediated by NADPH-oxidase derived ROS and vasoconstrictor prostanoids derived from COX-2, which are capable of reducing the vasorelaxation induced by SNP. Additionally, we found that ROS mediate the activation of NF-κB and the production of TNF-α in tolerant arteries. These findings identify putative molecular mechanisms whereby SNP induces tolerance in the vasculature. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of atherosclerosis on endothelium-dependent inhibition of platelet activation in humans.

PubMed

Diodati, J G; Dakak, N; Gilligan, D M; Quyyumi, A A

1998-07-07

We investigated whether luminal release of nitric oxide (NO) contributes to inhibition of platelet activation and whether these effects are reduced in patients with atherosclerosis. Femoral blood flow velocity and ex vivo whole blood platelet aggregation by impedance aggregometry were measured in femoral venous blood during femoral arterial infusion of acetylcholine (ACh; 30 microg/min) in 30 patients, 19 of whom had angiographic atherosclerosis. Measurements were repeated with sodium nitroprusside (40 microg/min), L-arginine (160 micromol/min), and N(G)-monomethyl-L-arginine (L-NMMA; 16 micromol/min). There was significant inhibition of collagen-induced platelet aggregation with ACh (45+/-9.5% lower, P<0.001), and this inhibition was greater in patients without atherosclerosis (68.7+/-10.4% reduction) than in those with atherosclerosis (32.5+/-8.1%, P=0.04). The magnitude of inhibition correlated with vasodilation with ACh, indicating an association between the smooth muscle and antiplatelet effects of endothelium-dependent stimulation. Neither L-NMMA nor sodium nitroprusside altered platelet aggregation. L-Arginine inhibited platelet aggregation equally in vitro (34+/-8% reduction, P<0.01) and in vivo (37+/-13% reduction, P<0.01). Stimulation of NO release into the vascular lumen with ACh inhibits platelet aggregation, an effect that is attenuated in patients with atherosclerosis and endothelial dysfunction. Basal NO release does not appear to contribute to platelet passivation in vivo. L-Arginine inhibited platelet aggregation by its direct action on platelets. These findings provide a pathophysiological basis for the observed increase in thrombotic events in atherosclerosis. Use of L-arginine and other strategies to improve endothelial NO activity may impact favorably on thrombotic events in atherosclerosis.

In vitro cytoprotective effects of acetylsalicylic acid, carprofen, meloxicam, or robenacoxib against apoptosis induced by sodium nitroprusside in canine cruciate ligament cells.

PubMed

Waldherr, Katrin; Zurbriggen, Andreas; Spreng, David E; Forterre, Simone

2012-11-01

To determine whether incubation of cruciate ligament cells with acetylsalicylic acid, carprofen, meloxicam, or robenacoxib provides protection against apoptosis induced by sodium nitroprusside (SNP). Explants of cranial (CCL) and caudal (CaCL) cruciate ligaments from eight 1-day-old Beagles. Primary cultures of CCL and CaCL cells were created via enzymatic dissociation of cruciate explants. Purified cell cultures were incubated for 2 hours without (controls) or with 1 of 3 concentrations of 1 of 4 NSAIDs (10, 100, or 200 μg of acetylsalicylic acid/mL; 0.1, 1, or 10 μg of carprofen/mL; 0.1, 1, or 10 μg of meloxicam/mL; or 0.1, 1, or 10 μg of robenacoxib/mL) and subsequently incubated for 18 hours with 1 of 3 concentrations of SNP in an attempt to induce mild, moderate, or severe cytotoxic effects. Cell viability and apoptosis were analyzed via a cell proliferation assay and flow cytometry, respectively. Prostaglandin E(2) concentrations were measured via an ELISA. Cytoprotective effects of NSAIDs were dependent on the extent of SNP-induced apoptosis and were greatest in CCL and CaCL cell cultures with moderate SNP-induced cytotoxic effects. Preincubation with an NSAID improved cell viability by 15% to 45% when CCL and CaCL cells were subsequently incubated with SNP. Carprofen (10 μg/mL) had the greatest cytoprotective effects for CCL and CaCL cells. Incubation with NSAIDs resulted in a nonsignificant decrease in PGE(2) production from SNP-damaged cells. Results indicated that carprofen, meloxicam, and robenacoxib may reduce apoptosis in cells originating from canine cruciate ligaments.

Pharmacological and histological examinations of regional differences of guinea-pig lung: a role of pleural surface smooth muscle in lung strip contraction.

PubMed Central

Wong, W. S.; Bloomquist, S. L.; Bendele, A. M.; Fleisch, J. H.

1992-01-01

1. Parenchymal lung strip preparations have been widely used as an in vitro model of peripheral airway smooth muscle. The present study examined functional responses of 4 consecutive guinea-pig lung parenchymal strips isolated from the central region (segment 1) to the distal edge (segment 4) of the lower lung lobe. The middle two segments were designated as segments 2 and 3. 2. Lung segments 1 and 4 exhibited significantly greater contraction than the other 2 segments to KCl when responses were expressed as mg force per mg tissue weight. Contractile responses to bronchospastic agents including histamine, carbachol, endothelin-1, leukotrienes (LT) B4 and D4, and the thromboxane A2-mimetic U46619 demonstrated no significant difference in EC50 values among the 4 lung segments. 3. Contractile responses of segments 1 and 4 to antigen-challenge (ovalbumin), ionophore A23187 and substance P were significantly greater than the other 2 segments with respect to either sensitivity or maximum responsiveness. 4. U46619-induced contractions of the 4 lung segments were relaxed in similar manner by papaverine and theophylline up to 100%, salbutamol up to 80%, and sodium nitroprusside by only 20%. In contrast, sodium nitroprusside markedly reversed U46619-induced contraction of pulmonary arterial rings and bronchial rings. 5. Histological studies identified 2-4 layers of smooth muscle cells underlying the lung pleural surface. Mast cells were prominent in this area. Moreover, morphometric studies showed that segment 4 possessed the least amount of smooth muscle structures from bronchial/bronchiolar wall and vasculatures as compared to the other 3 segments, and a significant difference in this respect was evident between segment 1 and segment 4.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 6 PMID:1378341

Dissociation between neural and vascular responses to sympathetic stimulation : contribution of local adrenergic receptor function

NASA Technical Reports Server (NTRS)

Jacob, G.; Costa, F.; Shannon, J.; Robertson, D.; Biaggioni, I.

2000-01-01

Sympathetic activation produced by various stimuli, eg, mental stress or handgrip, evokes regional vascular responses that are often nonhomogeneous. This phenomenon is believed to be the consequence of the recruitment of differential central neural pathways or of a sympathetically mediated vasodilation. The purpose of this study was to determine whether a similar heterogeneous response occurs with cold pressor stimulation and to test the hypothesis that local differences in adrenergic receptor function could be in part responsible for this diversity. In 8 healthy subjects, local norepinephrine spillover and blood flow were measured in arms and legs at baseline and during sympathetic stimulation induced by baroreflex mechanisms (nitroprusside infusion) or cold pressor stimulation. At baseline, legs had higher vascular resistance (27+/-5 versus 17+/-2 U, P=0.05) despite lower norepinephrine spillover (0.28+/-0.04 versus 0.4+/-0.05 mg. min(-1). dL(-1), P=0.03). Norepinephrine spillover increased similarly in both arms and legs during nitroprusside infusion and cold pressor stimulation. On the other hand, during cold stimulation, vascular resistance increased in arms but not in legs (20+/-9% versus -7+/-4%, P=0.03). Increasing doses of isoproterenol and phenylephrine were infused intra-arterially in arms and legs to estimate beta-mediated vasodilation and alpha-induced vasoconstriction, respectively. beta-Mediated vasodilation was significantly lower in legs compared with arms. Thus, we report a dissociation between norepinephrine spillover and vascular responses to cold stress in lower limbs characterized by a paradoxical decrease in local resistance despite increases in sympathetic activity. The differences observed in adrenergic receptor responses cannot explain this phenomenon.

Sodium Nitroprusside Enhanced Cardiopulmonary Resuscitation Improves Short Term Survival in a Porcine Model of Ischemic Refractory Ventricular Fibrillation

PubMed Central

Yannopoulos, Demetris; Bartos, Jason A.; George, Stephen A.; Sideris, George; Voicu, Sebastian; Oestreich, Brett; Matsuura, Timothy; Shekar, Kadambari; Rees, Jennifer; Aufderheide, Tom P.

2017-01-01

Introduction Sodium nitroprusside (SNP) enhanced CPR (SNPeCPR) demonstrates increased vital organ blood flow and survival in multiple porcine models. We developed a new, coronary occlusion/ischemia model of prolonged resuscitation, mimicking the majority of out-of-hospital cardiac arrests presenting with shockable rhythms. Hypothesis SNPeCPR will increase short term (4-hour) survival compared to standard 2015 Advanced Cardiac Life Support (ACLS) guidelines in an ischemic refractory ventricular fibrillation (VF), prolonged CPR model. Methods Sixteen anesthetized pigs had the ostial left anterior descending artery occluded leading to ischemic VF arrest. VF was untreated for 5 minutes. Basic life support was performed for 10 minutes. At minute 10 (EMS arrival), animals received either SNPeCPR (n=8) or standard ACLS (n=8). Defibrillation (200J) occurred every 3 minutes. CPR continued for a total of 45 minutes, then the balloon was deflated simulating revascularization. CPR continued until return of spontaneous circulation (ROSC) or a total of 60 minutes, if unsuccessful. SNPeCPR animals received 2 mg of SNP at minute 10 followed by 1 mg every 5 minutes until ROSC. Standard ACLS animals received 0.5 mg epinephrine every 5 minutes until ROSC. Primary endpoints were ROSC and 4-hour survival. Results All SNPeCPR animals (8/8) achieved sustained ROSC versus 2/8 standard ACLS animals within one hour of resuscitation (p=0.04). The 4-hour survival was significantly improved with SNPeCPR compared to standard ACLS, 7/8 versus 1/8 respectively, p=0.0019. Conclusion SNPeCPR significantly improved ROSC and 4-hour survival compared with standard ACLS CPR in a porcine model of prolonged ischemic, refractory VF cardiac arrest. PMID:27771299

Sodium nitroprusside enhanced cardiopulmonary resuscitation improves short term survival in a porcine model of ischemic refractory ventricular fibrillation.

PubMed

Yannopoulos, Demetris; Bartos, Jason A; George, Stephen A; Sideris, George; Voicu, Sebastian; Oestreich, Brett; Matsuura, Timothy; Shekar, Kadambari; Rees, Jennifer; Aufderheide, Tom P

2017-01-01

Sodium nitroprusside (SNP) enhanced CPR (SNPeCPR) demonstrates increased vital organ blood flow and survival in multiple porcine models. We developed a new, coronary occlusion/ischemia model of prolonged resuscitation, mimicking the majority of out-of-hospital cardiac arrests presenting with shockable rhythms. SNPeCPR will increase short term (4-h) survival compared to standard 2015 Advanced Cardiac Life Support (ACLS) guidelines in an ischemic refractory ventricular fibrillation (VF), prolonged CPR model. Sixteen anesthetized pigs had the ostial left anterior descending artery occluded leading to ischemic VF arrest. VF was untreated for 5min. Basic life support was performed for 10min. At minute 10 (EMS arrival), animals received either SNPeCPR (n=8) or standard ACLS (n=8). Defibrillation (200J) occurred every 3min. CPR continued for a total of 45min, then the balloon was deflated simulating revascularization. CPR continued until return of spontaneous circulation (ROSC) or a total of 60min, if unsuccessful. SNPeCPR animals received 2mg of SNP at minute 10 followed by 1mg every 5min until ROSC. Standard ACLS animals received 0.5mg epinephrine every 5min until ROSC. Primary endpoints were ROSC and 4-h survival. All SNPeCPR animals (8/8) achieved sustained ROSC versus 2/8 standard ACLS animals within one hour of resuscitation (p=0.04). The 4-h survival was significantly improved with SNPeCPR compared to standard ACLS, 7/8 versus 1/8 respectively, p=0.0019. SNPeCPR significantly improved ROSC and 4-h survival compared with standard ACLS CPR in a porcine model of prolonged ischemic, refractory VF cardiac arrest. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Antioxidant properties of Taraxacum officinale fruit extract are involved in the protective effect against cellular death induced by sodium nitroprusside in brain of rats.

PubMed

Colle, Dirleise; Arantes, Letícia Priscilla; Rauber, Ricardo; de Mattos, Sérgio Edgar Campos; Rocha, João Batista Teixeira da; Nogueira, Cristina Wayne; Soares, Félix Alexandre Antunes

2012-07-01

Taraxacum officinale Weber (Asteraceae), known as dandelion, is used for medicinal purposes due to its choleretic, diuretic, antitumor, antioxidant, antiinflammatory, and hepatoprotective properties. We sought to investigate the protective activity of T. officinale fruit extract against sodium nitroprusside (SNP)-induced decreased cellular viability and increased lipid peroxidation in the cortex, hippocampus, and striatum of rats in vitro. To explain the mechanism of the extract's antioxidant activity, its putative scavenger activities against NO, DPPH·, OH·, and H(2)O(2) were determined. Slices of cortex, hippocampus, and striatum were treated with 50 μM SNP and T. officinale fruit ethanolic extract (1-20 µg/mL) to determine cellular viability by MTT reduction assay. Lipid peroxidation was measure in cortical, hippocampal and striatal slices incubates with SNP (5 µM) and T. officinale fruit extract (1-20 µg/mL). We also determined the scavenger activities of T. officinale fruit extract against NO·, DPPH·, OH·, and H(2)O(2), as well as its iron chelating capacity. The extract (1, 5, 10, and 20 μg/mL) protected against SNP-induced decreases in cellular viability and increases in lipid peroxidation in the cortex, hippocampus, and striatum of rats. The extract had scavenger activity against DPPH· and NO· at low concentrations and was able to protect against H(2)O(2) and Fe(2+)-induced deoxyribose oxidation. T. officinale fruit extract has antioxidant activity and protects brain slices against SNP-induced cellular death. Possible mechanisms of action include its scavenger activities against reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are attributed to the presence of phenolic compounds in the extract.

Determination of chlorine in silicate rocks

USGS Publications Warehouse

Peck, L.C.

1959-01-01

In a rapid accurate method for the determination of chlorine in silicate rocks, the rock powder is sintered with a sodium carbonate flux containing zinc oxide and magnesium carbonate. The sinter cake is leached with water, the resulting solution is filtered, and the filtrate is acidified with nitric acid. Chlorine is determined by titrating this solution with mercuric nitrate solution using sodium nitroprusside as the indicator. The titration is made in the dark with a beam of light shining through the solution. The end point of the titration is found by visually comparing the intensity of this beam of light with that of a similar beam of light in a reference solution.

[NO donors transform neuronal response to glutamate].

PubMed

D'iakonova, T L

1998-10-01

Electrophysiological experiments on three identified neurones were performed. Two NO donors, sodium nitroprusside (SNP) and sodium nitrite, as well as NO synthase inhibitor, were used. In each neurone, bath application of glutamate caused hyperpolarization and suppression of firing. Combined application of glutamate and SNP resulted in that the same cells responded to identical glutamate solutions with depolarization and excitation. Application of N-monomethyl-L-arginin (NMMA) arrested the glutamate-induced firing and depolarization. The findings suggest involvement of NO in the mechanism of transformation of glutamate-induced inhibition into excitation and a mediation of the latter by the N-methyl-D-aspartate-like receptors in the Helix brain.

Renal sympathetic nerve activity measured by norepinephrine spillover rate in response to changes in blood pressure in conscious rabbits.

PubMed

Sano, N; Way, D; McGrath, B P

1989-04-01

1. Renal sympathetic nerve activity (RSNA) in response to changes in mean arterial pressure (MAP) was examined by measuring renal norepinephrine (NE) spillover rate in conscious rabbits. 2. A chronic renal vein catheter was implanted for sampling renal venous blood without stress in conscious animals. 3. RSNA estimated by renal NE spillover rate significantly increased in response to moderate falls in MAP produced by sodium nitroprusside (SNP) infusion and decreased in response to moderate rises in MAP produced by phenylephrine (PE) infusion. 4. The NE spillover method is sufficiently sensitive to detect responses of RSNA to physiological stimuli in conscious rabbits.

Insufficient sleep is associated with impaired nitric oxide-mediated endothelium-dependent vasodilation.

PubMed

Bain, Anthony R; Weil, Brian R; Diehl, Kyle J; Greiner, Jared J; Stauffer, Brian L; DeSouza, Christopher A

2017-10-01

Habitual short nightly sleep duration is associated with increased atherosclerotic cardiovascular disease risk and morbidity. Vascular endothelial dysfunction represents an important mechanism that may underlie this heightened cardiovascular risk. Impaired endothelium-dependent vasodilation, particularly NO-mediated vasodilation, contributes to the development and progression of atherosclerotic vascular disease and acute vascular events. We tested the hypothesis that chronic insufficient sleep is associated with impaired NO-mediated endothelium-dependent vasodilation in middle-aged adults. Thirty adult men were studied: 15 with normal nightly sleep duration (age: 58 ± 2 y; sleep duration: 7.7 ± 0.2 h/night) and 15 with short nightly sleep duration (55 ± 2 y; 6.1 ± 0.2 h/night). Forearm blood flow (FBF) responses to intra-arterial infusion of acetylcholine, in the absence and presence of the endothelial NO synthase inhibitor N G -monomethyl-L-arginine (L-NMMA), as well as responses to sodium nitroprusside, were determined by strain-gauge venous occlusion plethysmography. The FBF response to acetylcholine was lower (∼20%; p<0.05) in the short sleep duration group (from 4.6 ± 0.3 to 11.7 ± 1.0 ml/100 ml tissue/min) compared with normal sleep duration group (from 4.4 ± 0.3 to 14.5 ± 0.5 ml/100 ml tissue/min). L-NMMA significantly reduced the FBF response to acetylcholine in the normal sleep duration group (∼40%), but not the short sleep duration group. There were no group differences in the vasodilator response to sodium nitroprusside. These data indicate that short nightly sleep duration is associated with endothelial-dependent vasodilator dysfunction due, in part, to diminished NO bioavailability. Impaired NO-mediated endothelium-dependent vasodilation may contribute to the increased cardiovascular risk with insufficient sleep. Copyright © 2017 Elsevier B.V. All rights reserved.

Chiral recognition of pinacidil and its 3-pyridyl isomer by canine cardiac and smooth muscle: Antagonism by sulfonylureas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinberg, M.I.; Wiest, S.A.; Zimmerman, K.M.

1991-01-01

Pinacidil, a potassium channel opener (PCO), relaxes vascular smooth muscle by increasing potassium ion membrane conductance, thereby causing membrane hyperpolarization. PCOs also act on cardiac muscle to decrease action potential duration (APD) selectively. To examine the enantiomeric selectivity of pinacidil, the stereoisomers of pinacidil (a 4-pyridylcyanoguanidine) and its 3-pyridyl isomer (LY222675) were synthesized and studied in canine Purkinje fibers and cephalic veins. The (-)-enantiomers of both pinacidil and LY222675 were more potent in relaxing phenylephrine-contracted cephalic veins and decreasing APD than were their corresponding (+)-enantiomers. The EC50 values for (-)-pinacidil and (-)-LY222675 in relaxing cephalic veins were 0.44 and 0.09more » microM, respectively. In decreasing APD, the EC50 values were 3.2 microM for (-)-pinacidil and 0.43 microM for (-)-LY222675. The eudismic ratio was greater for the 3-pyridyl isomer than for pinacidil in both cardiac (71 vs. 22) and vascular (53 vs. 17) tissues. (-)-LY222675 and (-)-pinacidil (0.1-30 microM) also increased 86Rb efflux from cephalic veins to a greater extent than did their respective optical antipodes. The antidiabetic sulfonylurea, glyburide (1-30 microM), shifted the vascular concentration-response curve of (-)-pinacidil to the right by a similar extent at each inhibitor concentration. Glipizide also antagonized the response to (-)-pinacidil, but was about 1/10 as potent with a maximal shift occurring at 10 and 30 microM. Glyburide antagonized the vascular relaxant effects of 0.3 microM (-)-LY222675 (EC50, 2.3 microM) and reversed the decrease in APD caused by 3 microM (-)-LY222675 (EC50, 1.9 microM). Nitroprusside did not alter 86Rb efflux, and vascular relaxation induced by sodium nitroprusside was unaffected by sulfonylureas.« less

Favorable Vascular Actions of Angiotensin-(1-7) in Human Obesity.

PubMed

Schinzari, Francesca; Tesauro, Manfredi; Veneziani, Augusto; Mores, Nadia; Di Daniele, Nicola; Cardillo, Carmine

2018-01-01

Obese patients have vascular dysfunction related to impaired insulin-stimulated vasodilation and increased endothelin-1-mediated vasoconstriction. In contrast to the harmful vascular actions of angiotensin (Ang) II, the angiotensin-converting enzyme 2 product Ang-(1-7) has shown to exert cardiovascular and metabolic benefits in experimental models through stimulation of the Mas receptor. We, therefore, examined the effects of exogenous Ang-(1-7) on vasodilator tone and endothelin-1-dependent vasoconstriction in obese patients. Intra-arterial infusion of Ang-(1-7) (10 nmol/min) resulted in significant increase in unstimulated forearm flow ( P =0.03), an effect that was not affected by the Mas receptor antagonist A779 (10 nmol/min; P >0.05). In the absence of hyperinsulinemia, however, forearm flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during Ang-(1-7) administration compared with saline (both P >0.05). During infusion of regular insulin (0.15 mU/kg per minute), by contrast, endothelium-dependent vasodilator response to acetylcholine was significantly enhanced by Ang-(1-7) ( P =0.04 versus saline), whereas endothelium-independent response to sodium nitroprusside was not modified ( P =0.91). Finally, Ang-(1-7) decreased the vasodilator response to endothelin A receptor blockade (BQ-123; 10 nmol/min) compared with saline (6±1% versus 93±17%; P <0.001); nitric oxide inhibition by l- N -monomethylarginine (4 µmol/min) during concurrent endothelin A antagonism resulted in similar vasoconstriction in the absence or presence of Ang-(1-7 Ang-(1-7) ( P =0.69). Our findings indicate that in obese patients Ang-(1-7) has favorable effects not only to improve insulin-stimulated endothelium-dependent vasodilation but also to blunt endothelin-1-dependent vasoconstrictor tone. These findings provide support for targeting Ang-(1-7) to counteract the hemodynamic abnormalities of human obesity. © 2017 American Heart Association, Inc.

Necrosis is increased in lymphoblastoid cell lines from children with autism compared with their non-autistic siblings under conditions of oxidative and nitrosative stress.

PubMed

Main, Penelope A E; Thomas, Philip; Esterman, Adrian; Fenech, Michael F

2013-07-01

Autism spectrum disorders are a heterogeneous group of neurodevelopmental conditions characterised by impairments in reciprocal social interaction, communication and stereotyped behaviours. As increased DNA damage events have been observed in a range of other neurological disorders, it was hypothesised that they would be elevated in lymphoblastoid cell lines (LCLs) obtained from children with autism compared with their non-autistic siblings. Six case-sibling pairs of LCLs from children with autistic disorder and their non-autistic siblings were obtained from the Autism Genetic Resource Exchange (AGRE) and cultured in standard RPMI-1640 tissue culture medium. Cells were exposed to medium containing either 0, 25, 50, 100 and 200 µM hydrogen peroxide (an oxidative stressor) or 0, 5, 10, 20 and 40 µM s-nitroprusside (a nitric oxide producer) for 1h. Following exposure, the cells were microscopically scored for DNA damage, cytostasis and cytotoxicity biomarkers as measured using the cytokinesis-block micronucleus cytome assay. Necrosis was significantly increased in cases relative to controls when exposed to oxidative and nitrosative stress (P = 0.001 and 0.01, respectively). Nuclear division index was significantly lower in LCLs from children with autistic disorder than their non-autistic siblings when exposed to hydrogen peroxide (P = 0.016), but there was no difference in apoptosis, micronucleus frequency, nucleoplasmic bridges or nuclear buds. Exposure to s-nitroprusside significantly increased the number of micronuclei in non-autistic siblings compared with cases (P = 0.003); however, other DNA damage biomarkers, apoptosis and nuclear division did not differ significantly between groups. The findings of this study show (i) that LCLs from children with autism are more sensitive to necrosis under conditions of oxidative and nitrosative stress than their non-autistic siblings and (ii) refutes the hypothesis that children with autistic disorder are abnormally susceptible to DNA damage.

Necrosis is increased in lymphoblastoid cell lines from children with autism compared with their non-autistic siblings under conditions of oxidative and nitrosative stress

PubMed Central

Fenech, Michael F.

2013-01-01

Autism spectrum disorders are a heterogeneous group of neurodevelopmental conditions characterised by impairments in reciprocal social interaction, communication and stereotyped behaviours. As increased DNA damage events have been observed in a range of other neurological disorders, it was hypothesised that they would be elevated in lymphoblastoid cell lines (LCLs) obtained from children with autism compared with their non-autistic siblings. Six case–sibling pairs of LCLs from children with autistic disorder and their non-autistic siblings were obtained from the Autism Genetic Resource Exchange (AGRE) and cultured in standard RPMI-1640 tissue culture medium. Cells were exposed to medium containing either 0, 25, 50, 100 and 200 µM hydrogen peroxide (an oxidative stressor) or 0, 5, 10, 20 and 40 µM s-nitroprusside (a nitric oxide producer) for 1h. Following exposure, the cells were microscopically scored for DNA damage, cytostasis and cytotoxicity biomarkers as measured using the cytokinesis-block micronucleus cytome assay. Necrosis was significantly increased in cases relative to controls when exposed to oxidative and nitrosative stress (P = 0.001 and 0.01, respectively). Nuclear division index was significantly lower in LCLs from children with autistic disorder than their non-autistic siblings when exposed to hydrogen peroxide (P = 0.016), but there was no difference in apoptosis, micronucleus frequency, nucleoplasmic bridges or nuclear buds. Exposure to s-nitroprusside significantly increased the number of micronuclei in non-autistic siblings compared with cases (P = 0.003); however, other DNA damage biomarkers, apoptosis and nuclear division did not differ significantly between groups. The findings of this study show (i) that LCLs from children with autism are more sensitive to necrosis under conditions of oxidative and nitrosative stress than their non-autistic siblings and (ii) refutes the hypothesis that children with autistic disorder are abnormally susceptible to DNA damage. PMID:23766106

The neuropathic postural tachycardia syndrome

NASA Technical Reports Server (NTRS)

Jacob, G.; Costa, F.; Shannon, J. R.; Robertson, R. M.; Wathen, M.; Stein, M.; Biaggioni, I.; Ertl, A.; Black, B.; Robertson, D.

2000-01-01

BACKGROUND: The postural tachycardia syndrome is a common disorder that is characterized by chronic orthostatic symptoms and a dramatic increase in heart rate on standing, but that does not involve orthostatic hypotension. Several lines of evidence indicate that this disorder may result from sympathetic denervation of the legs. METHODS: We measured norepinephrine spillover (the rate of entry of norepinephrine into the venous circulation) in the arms and legs both before and in response to exposure to three stimuli (the cold pressor test, sodium nitroprusside infusion, and tyramine infusion) in 10 patients with the postural tachycardia syndrome and in 8 age- and sex-matched normal subjects. RESULTS: At base line, the mean (+/-SD) plasma norepinephrine concentration in the femoral vein was lower in the patients with the postural tachycardia syndrome than in the normal subjects (135+/-30 vs. 215+/-55 pg per milliliter [0.80+/-0.18 vs. 1.27+/-0.32 nmol per liter], P=0.001). Norepinephrine spillover in the arms increased to a similar extent in the two groups in response to each of the three stimuli, but the increases in the legs were smaller in the patients with the postural tachycardia syndrome than in the normal subjects (0.001+/-0.09 vs. 0.12+/-0.12 ng per minute per deciliter of tissue [0.006+/-0.53 vs. 0.71+/-0.71 nmol per minute per deciliter] with the cold pressor test, P=0.02; 0.02+/-0.07 vs. 0.23+/-0.17 ng per minute per deciliter [0.12+/-0.41 vs. 1.36+/-1.00 nmol per minute per deciliter] with nitroprusside infusion, P=0.01; and 0.008+/-0.09 vs. 0.19+/-0.25 ng per minute per deciliter [0.05+/-0.53 vs. 1.12+/-1.47 nmol per minute per deciliter] with tyramine infusion, P=0.04). CONCLUSIONS: The neuropathic postural tachycardia syndrome results from partial sympathetic denervation, especially in the legs.

Inhibition of overexpression of Giα proteins and nitroxidative stress contribute to sodium nitroprusside-induced attenuation of high blood pressure in SHR.

PubMed

Hossain, Ekhtear; Sarkar, Oli; Li, Yuan; Anand-Srivastava, Madhu B

2018-03-01

We earlier showed that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit enhanced expression of Giα proteins which was attributed to the decreased levels of nitric oxide (NO), because elevation of the intracellular levels of NO by NO donors; sodium nitroprusside (SNP) and S-Nitroso-N-acetyl-DL-penicillamine (SNAP), attenuated the enhanced expression of Giα proteins. Since the enhanced expression of Giα proteins is implicated in the pathogenesis of hypertension, the present study was undertaken to investigate if treatment of SHR with SNP could also attenuate the development of high blood pressure (BP) and explore the underlying molecular mechanisms. Intraperitoneal injection of SNP at a concentration of 0.5 mg/kg body weight twice a week for 2 weeks into SHR attenuated the high blood pressure by about 80 mmHg without affecting the BP in WKY rats. SNP treatment also attenuated the enhanced levels of superoxide anion (O 2 - ), hydrogen peroxide (H 2 O 2 ), peroxynitrite (ONOO - ), and NADPH oxidase activity in VSMC from SHR to control levels. In addition, the overexpression of different subunits of NADPH oxidase; Nox-1, Nox-2, Nox-4, P 22phox , and P 47phox , and Giα proteins in VSMC from SHR were also attenuated by SNP treatment. On the other hand, SNP treatment augmented the decreased levels of intracellular NO, eNOS, and cGMP in VSMC from SHR. These results suggest that SNP treatment attenuates the development of high BP in SHR through the elevation of intracellular levels of cGMP and inhibition of the enhanced levels of Giα proteins and nitroxidative stress. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Sodium nitroprusside increases human skeletal muscle blood flow, but does not change flow distribution or glucose uptake.

PubMed

Pitkanen, O P; Laine, H; Kemppainen, J; Eronen, E; Alanen, A; Raitakari, M; Kirvela, O; Ruotsalainen, U; Knuuti, J; Koivisto, V A; Nuutila, P

1999-12-15

1. The role of blood flow as a determinant of skeletal muscle glucose uptake is at present controversial and results of previous studies are confounded by possible direct effects of vasoactive agents on glucose uptake. Since increase in muscle blood flow can be due to increased flow velocity or recruitment of new capillaries, or both, it would be ideal to determine whether the vasoactive agent affects flow distribution or only increases the mean flow. 2. In the present study blood flow, flow distribution and glucose uptake were measured simultaneously in both legs of 10 healthy men (aged 29 +/- 1 years, body mass index 24 +/- 1 kg m-2) using positron emission tomography (PET) combined with [15O]H2O and [18F]fluoro-2-deoxy-D-glucose (FDG). The role of blood flow in muscle glucose uptake was studied by increasing blood flow in one leg with sodium nitroprusside (SNP) and measuring glucose uptake simultaneously in both legs during euglycaemic hyperinsulinaemia (insulin infusion 6 pmol kg-1 min-1). 3. SNP infusion increased skeletal muscle blood flow by 86 % (P < 0.01), but skeletal muscle flow distribution and insulin-stimulated glucose uptake (61.4 +/- 7. 5 vs. 67.0 +/- 7.5 micromol kg-1 min-1, control vs. SNP infused leg, not significant), as well as flow distribution between different tissues of the femoral region, remained unchanged. The effect of SNP infusion on blood flow and distribution were unchanged during infusion of physiological levels of insulin (duration, 150 min). 4. Despite a significant increase in mean blood flow induced by an intra-arterial infusion of SNP, glucose uptake and flow distribution remained unchanged in resting muscles of healthy subjects. These findings suggest that SNP, an endothelium-independent vasodilator, increases non-nutritive, but not nutritive flow or capillary recruitment.

Presence of cardiovascular structural changes in essential hypertensive patients with coronary microvascular disease and effects of long-term treatment.

PubMed

Virdis, A; Ghiadoni, L; Lucarini, A; Di Legge, V; Taddei, S; Salvetti, A

1996-04-01

In asymptomatic essential hypertensive patients with angiographically normal coronary arteries and without left ventricular hypertrophy, dipyridamole-induced ischemic-like ST segment depression may be a marker of coronary microvascular disease. In this study we evaluated, first, whether this cardiac abnormality is linked to structural or functional vascular abnormalities, and second, the effect of antihypertensive treatment by 12-month administration of the angiotensin converting enzyme (ACE) inhibitor captopril (50 mg twice a day orally). In essential hypertensives with dipypridamole echocardiography stress test (DET) (DET+, n = 8) and without (DET-, n = 8) ST segment depression greater than 0.1 mV during intravenous dipyridamole infusion (0.84 mg/kg over 10 min), we studied the forearm blood flow (FBF, venous plethysmography, mL/100) modifications induced by intrabrachial acetylcholine (Ach) (0.15, 0.45, 1.5, 4.5, 15 micrograms/100 mL/min x 5 min each), an endothelium-dependent vasodilator, and by sodium nitroprusside (SNP) (1, 2, 4 micrograms/100 mL/min x 5 min each), a smooth muscle cell relaxant compound. Minimal forearm vascular resistances (MFVR), an index of arteriolar structural changes, were also calculated. Both Ach and SNP caused greater vasodilation in DET- as compared to DET+ while MFVRs were lower in DET- compared to DET+. After treatment, both DET+ and DET- patients showed a significant and similar reduction in blood pressure and left ventricular mass index, while vasodilation to acetylcholine and sodium nitroprusside was increased only in the DET+ group. In addition, forearm minimal vascular resistances were significantly reduced only in DET+ patients, who showed disappearance of dipyridamole-induced ischemic-like ST segment depression. In conclusion, these data confirm that essential hypertensive patients with microvascular coronary disease are characterized by the presence of structural changes in the forearm vascular bed. Our results also indicate that both cardiac and forearm vascular abnormalities can be reversed by antihypertensive treatment with an ACE inhibitor.

Effects of chronic administration of ethanolic extract of kolanut (Cola nitida) and caffeine on vascular function.

PubMed

Salahdeen, H M; Omoaghe, A O; Isehunwa, G O; Murtala, B A; Alada, A R A

2014-03-01

Kolanut (Cola nitida) is consumed in virtually every part of the world. The caffeine content of kolanut is scarce and the number of investigations studying the health benefits of kolanut is negligible compared to coffee. The present study was designed to identify the caffeine content of kolanut and evaluate the effect of its chronic consumption on cardiovascular functions in rats. The caffeine content of kolanut was determined by Gas chromatography-mass spectrometry (GC-MS). Wistar albino rats were divided into four groups (10 Rats/group). Kolanut extract (11.9 mg/kg), caffeine extracted from kolanut (7.5 mg/kg), decaffeinated of kolanut extract (6 mg/kg) and distilled water (control) was administered orally to each group for six-weeks. Effect of treatment on body weight, blood pressure and relaxation response to acetylcholine (ACh) and sodium nitroprusside (SNP) of the aortic rings was assessed. The total caffeine content of kolanut extract was found to be 51% and it was 96% pure from GC-MS analysis. Chronic consumption of kolanut and caffeine significantly (p < 0.05) decreased body weight. Similarly, kolanut extract decaffeinated kolanut and caffeine significantly (p < 0.05) reduced the contractile response to noradrenaline and higher potassium solution. Kolanut extract and caffeine also significantly (p < 0.05) increased the mean arterial blood pressure. Caffeine and kolanut consumption reduced the relaxation response to both acetylcholine and sodium nitroprusside. Atropine and L-NAME considerably inhibit the ACh-induced relaxation of the rat aortic ring suggesting the involvement of cholinergic mechanism. However, indomethacin (10(-4)M) also attenuated the ACh response indicating involvement of protanoids. The results suggest that treatment with both kolanut extract and caffeine had similar characteristics between the two groups with no significant differences in the ACh-induced relaxation of thering suggesting that the action of kolanut extract is due to its caffeine content.

Effect of sodium nitroprusside and 8-bromo cyclic GMP on nerve-mediated and acetylcholine-evoked secretory responses in the rat pancreas

PubMed Central

Yago, Maria D; Tapia, Jose A; Salido, Gines M; Adeghate, Ernest; Juma, Lubna M O; Martinez-Victoria, Emilio; Mañas, Mariano; Singh, Jaipaul

2002-01-01

The effects of sodium nitroprusside (SNP) and 8-bromo-guanosine 3′5′ cyclic monophosphate (8-Br-cyclic GMP) on nerve-mediated and acetylcholine (ACh)-evoked amylase secretion, tritiated choline ([3H]-choline) release and on intracellular free calcium concentration ([Ca2+]i) in the isolated rat pancreas were investigated.Electrical field stimulation (EFS; 10 Hz) and ACh (1×10−5 M) caused large increases in amylase output from pancreatic segments. The response to ACh was blocked by atropine (1×10−5 M) whereas the EFS-evoked response was markedly reduced but not abolished. In contrast, pretreatment with tetrodotoxin (1×10−6 M) abolished the secretory effect of EFS.Either SNP (1×10−3 M) or 8-Br-cyclic GMP (1×10−4 M) inhibited amylase secretion compared to basal. Combining either SNP or 8-Br-cyclic GMP with EFS resulted in a marked decrease in amylase output compared to EFS alone. In contrast, either SNP or 8-Br-cyclic GMP had no significant effect on the amylase response to ACh. When extracellular Ca2+ concentration ([Ca2+]o) was elevated from 2.56 mM to 5.12 mM, SNP failed to inhibit the response to EFS.EFS stimulated the release of 3H from pancreatic segments preloaded with [3H]-choline. Either SNP or 8-Br-cyclic GMP had no effect on basal 3H release but significantly reduced the EFS-evoked response.In fura-2 loaded acinar cells, SNP elicited a small decrease in [Ca2+]i compared to basal and had no effect on the ACh-induced [Ca2+]i peak response.Nitric oxide may modulate the release of endogenous neural ACh in response to EFS in the rat pancreas. PMID:11976267

Protective effect of N-acetylcysteine against oxygen radical-mediated coronary artery injury.

PubMed

Rodrigues, A J; Evora, P R B; Schaff, H V

2004-08-01

The present study investigated the protective effect of N-acetylcysteine (NAC) against oxygen radical-mediated coronary artery injury. Vascular contraction and relaxation were determined in canine coronary arteries immersed in Kreb's solution (95% O2-5% CO2), incubated or not with NAC (10 mM), and exposed to free radicals (FR) generated by xanthine oxidase (100 mU/ml) plus xanthine (0.1 mM). Rings not exposed to FR or NAC were used as controls. The arteries were contracted with 2.5 microM prostaglandin F2alpha. Subsequently, concentration-response curves for acetylcholine, calcium ionophore and sodium fluoride were obtained in the presence of 20 microM indomethacin. Concentration-response curves for bradykinin, calcium ionophore, sodium nitroprusside, and pinacidil were obtained in the presence of indomethacin plus Nomega-nitro-L-arginine (0.2 mM). The oxidative stress reduced the vascular contraction of arteries not exposed to NAC (3.93 +/- 3.42 g), compared to control (8.56 +/- 3.16 g) and to NAC group (9.07 +/- 4.0 g). Additionally, in arteries not exposed to NAC the endothelium-dependent nitric oxide (NO)-dependent relaxation promoted by acetylcholine (1 nM to 10 microM) was also reduced (maximal relaxation of 52.1 +/- 43.2%), compared to control (100%) and NAC group (97.0 +/- 4.3%), as well as the NO/cyclooxygenase-independent receptor-dependent relaxation provoked by bradykinin (1 nM to 10 microM; maximal relaxation of 20.0 +/- 21.2%), compared to control (100%) and NAC group (70.8 +/- 20.0%). The endothelium-independent relaxation elicited by sodium nitroprusside (1 nM to 1 microM) and pinacidil (1 nM to 10 microM) was not affected. In conclusion, the vascular dysfunction caused by the oxidative stress, expressed as reduction of the endothelium-dependent relaxation and of the vascular smooth muscle contraction, was prevented by NAC.

Effects of perilymphatic pressure, sodium nitroprusside, and bupivacaine on cochlear fluid pH of guinea pigs.

PubMed

Suzuki, Masaaki; Kotani, Ryosuke

2015-01-01

Hydrostatic positive pressure and vasoconstrictor acidified the cochlear fluids, whereas the vasodilator made the fluids alkaline. CBF might play a role in regulating cochlea fluid pH. Cochlea fluid pH is highly dependent on the HCO3(-)/CO2 buffer system. Cochlear blood flow (CBF) supplies O2 and removes CO2. It is speculated that cochlear blood flow changes might affect the balance of the HCO3(-)/CO2 buffer system in the cochlea. It is known that the elevation of inner ear pressure decreases the CBF, and local application of vasodilating or vasoconstricting agents directly to the cochlea changes the CBF. The purpose of this study was to elucidate the effect of positive hydrostatic inner ear pressure and application of a vasodilator and vasoconstrictor of cochlear vessels on the pH of the endolymph and perilymph. The authors performed animal physiological experiments on 30 guinea pigs. Hydrostatic positive pressure was infused through a glass capillary tube inserted into the scala tympani of the basal turn. The vasodilator, nitric oxide donor (sodium nitroprusside; SNP), and the vasoconstrictor, bupivacaine, were placed topically onto the round window of the guinea pig cochlea. Endolymph pH (pHe) and endocochlear potential (EP) were monitored by double-barreled ion-selective microelectrodes in the second turn of the guinea pig cochlea. During the topical application study, scala vestibuli perilymph pH (pHv) was also measured simultaneously in the second turn. The application of hydrostatic positive pressure caused a decrease in pHe and EP. Positive perilymphatic pressure caused the endolymph to become acidic pressure-dependently. Application of 3.0% SNP evoked an increase in both the pHe and pHv, following by a gradual recovery to baseline levels. On the other hand, 0.5% bupivacaine caused a decrease in both the pHe and pHv. The EP during topical application showed slight, non-significant changes.

Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside

PubMed Central

Chantler, Paul D.; Nussbacher, Amit; Gerstenblith, Gary; Schulman, Steven P.; Becker, Lewis C.; Ferrucci, Luigi; Fleg, Jerome L.; Najjar, Samer S.

2011-01-01

The coupling between arterial elastance (EA; net afterload) and left ventricular elastance (ELV; pump performance), known as EA/ELV, is a key determinant of cardiovascular performance and shifts during exercise due to a greater increase in ELV versus EA. This normal exercise-induced reduction in EA/ELV decreases with advancing age. We hypothesized that sodium nitroprusside (SNP) can acutely ameliorate the age-associated deficits in EA/ELV. At rest and during graded exercise to exhaustion, EA was characterized as end-systolic pressure/stroke volume and ELV as end-systolic pressure/end-systolic volume. Resting EA/ELV did not differ between old (70 ± 8 yr, n = 15) and young (30 ± 5 yr, n = 17) subjects because of a tandem increase in EA and ELV in older subjects. During peak exercise, a blunted increase in ELV in old (7.8 ± 3.1 mmHg/ml) versus young (11.4 ± 6.5 mmHg/ml) subjects blunted the normal exercise-induced decline in EA/ELV in old (0.25 ± 0.11) versus young (0.16 ± 0.05) subjects. SNP administration to older subjects lowered resting EA/ELV by 31% via a reduction in EA (10%) and an increase in ELV (47%) and lowered peak exercise EA/ELV (36%) via an increase in ELV (68%) without a change in EA. Importantly, SNP attenuated the age-associated deficits in EA/ELV and ELV during exercise, and at peak exercise EA/ELV in older subjects on drug administration did not differ from young subjects without drug administration. In conclusion, some age-associated deficiencies in EA/ELV, EA, and ELV, in older subjects can be acutely abolished by SNP infusion. This is relevant to common conditions in older subjects associated with a significant impairment of exercise performance such as frailty or heart failure with preserved ejection fraction. PMID:21378146

Relaxation of isolated guinea-pig trachea by apigenin, a constituent of celery, via inhibition of phosphodiesterase.

PubMed

Chen, Junn-Lain; Ko, Wun-Chang

2017-09-15

Apigenin, was reported to have vasodilatory effects by inhibiting Ca 2+ influx through both voltage- and receptor-operated calcium channels, but not by inhibiting cAMP- or cGMP-phosphodiesterases (PDEs) in rat thoracic aorta. However, apigenin was reported to inhibit PDE1, 2 and 3 in guinea-pig lung and heart. The aim of this study was to clarify that guinea-pig tracheal relaxation by apigenin whether via PDE inhibition. We isometrically recorded the tension of isolated guinea-pig tracheal segments on a polygraph. Antagonistic effects of apigenin against cumulative contractile agents or Ca 2+ induced contractions of the trachealis in normal or isotonic high-K + , Ca 2+ -free Krebs solution, respectively. Effects of apigenin (15 and 30μM) on the cumulative forskolin- and nitroprusside-induced relaxations to histamine (30μM)-induced precontraction were performed. The inhibitory effects of 30-300μM apigenin and 3-isobutyl-1-methylxanthine (IBMX, positive control) on the cAMP- and cGMP-PDEs were determined. Apigenin concentration-dependently but non-competitively inhibited cumulative histamine-, carbachol- or Ca 2+ -induced contractions in normal or in the depolarized (K + , 60mM) trachealis, suggesting that Ca 2+ influx through voltage-dependent calcium channels is inhibited. However, apigenin (15-30μM) parallel leftward shifted the concentration-response curves of forskolin and nitroprusside, and significantly increased the pD 2 values of these two cyclase activators. Both apigenin and IBMX, a reference drug, concentration (10-300μM)-dependently and significantly, but non-selectively inhibited the activities of cAMP- and cGMP-PDEs in the trachealis. In conclusion, the relaxant effect of apigenin may be due to inhibition of both enzyme activities and reduction of intracellular Ca 2+ by inhibiting Ca 2+ influx in the trachealis. Copyright © 2017 Elsevier B.V. All rights reserved.

Hypoxia and alkalinization inhibit endothelium-derived nitric oxide but not endothelium-derived hyperpolarizing factor responses in porcine coronary artery.

PubMed

Shimizu, S; Paul, R J

1999-10-01

We investigated the mechanisms by which hypoxia and alkalinization inhibit the endothelium-dependent relaxation to Substance P (SP) in porcine coronary artery. In a KCl contracture, the major component of the SP response is endothelium-derived nitric oxide (EDNO), whereas with receptor-mediated 9,11-dideoxy-llalpha, 9alpha-epoxymethanoprostaglandin F(2alpha) (U46619) stimulation, the SP response is dependent on both EDNO and endothelium-derived hyperpolarization factor. Intracellular alkalinization by NH(4)Cl reduced the peak of SP responses when arteries were contracted with KCl, whereas with U46619 stimulation, the peak was little effected but the duration was shortened. In endothelial cell-denuded arteries, alkalinization with NH(4)Cl shifted the sodium nitroprusside concentration-relaxation relations rightward. The effects of NH(4)Cl in SP- and sodium nitroprusside-induced relaxations were attenuated by decreasing extracellular pH (pH(o)) from 7.4 to 7.2, which normalized intracellular pH (pH(i)) to control levels. In contrast, in U46619 contractures, the SP response in the presence of a NO synthase inhibitor was unaffected by NH(4)Cl. Moreover, hypoxia blunted but did not abolish the responses to SP for U46619 contractures; addition of KCl, however, abolished the SP response under hypoxia. Endothelial [Ca(2+)](i) was measured with fura-2 differentially loaded only into endothelial cells on intact arteries. Despite the attenuation of the SP response in KCl contractures by NH(4)Cl or hypoxia, endothelial [Ca(2+)](i) responses were unchanged. Our results suggest that hypoxia and alkalinization inhibit EDNO but not endothelium-derived hyperpolarization factor relaxations through a mechanism(s) not involving endothelial cell [Ca(2+)](i). Inhibition of EDNO relaxation by alkalinization with NH(4)Cl is likely to occur at the level of activation of guanylate cyclase and/or at a step downstream in smooth muscle.

Endothelium-dependent and independent vasorelaxant effects of aqueous extract of Tridax procumbens Lin. leaf in rat aortic rings.

PubMed

Salahdeen, Hussein M; Idowu, Gbolahan O; Murtala, Babatunde A

2012-12-01

Tridax procumbens leaf extract induced aortic relaxation in a concentration-dependent manner, for both phenylephrine (PE) and KCl- induced contractions in isolated rat aortic rings. The relaxation effect of the extract on PE-induced contraction was 57% greater than that on KCl- induced contraction. The extract caused dose-dependent relaxations in precontracted isolated rat aorta with phenylephrine; the relaxation was attenuated by the removal of endothelium. However, the relaxation responses to sodium nitroprusside were not significantly abolished by the removal of endothelium. The vasorelaxatory effect of the extract was completely abolished in presence of L-NAME. The results indicate that the vasorelaxant effect of T. procumbens extract is probably mediated by both endothelium-dependent and-independent mechanisms.

Recent developments in nitric oxide donor drugs

PubMed Central

Miller, M R; Megson, I L

2007-01-01

During the 1980s, the free radical, nitric oxide (NO), was discovered to be a crucial signalling molecule, with wide-ranging functions in the cardiovascular, nervous and immune systems. Aside from providing a credible explanation for the actions of organic nitrates and sodium nitroprusside that have long been used in the treatment of angina and hypertensive crises respectively, the discovery generated great hopes for new NO-based treatments for a wide variety of ailments. Decades later, however, we are still awaiting novel licensed agents in this arena, despite an enormous research effort to this end. This review explores some of the most promising recent advances in NO donor drug development and addresses the challenges associated with NO as a therapeutic agent. PMID:17401442

Inhibition of the gap junctional component of endothelium-dependent relaxations in rabbit iliac artery by 18-α glycyrrhetinic acid

PubMed Central

Taylor, Hannah J; Chaytor, Andrew T; Evans, W Howard; Griffith, Tudor M

1998-01-01

The gap junction inhibitor 18-α-glycyrrhetinic acid (α-GA, 100 μM) attenuated endothelium-dependent relaxations to acetylcholine and cyclopiazonic acid by ∼20% in rings of pre-constricted rabbit iliac artery. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 300 μM) inhibited relaxations to both agents by ∼65% and these were further attenuated by α-GA to <10% of control. In endothelium-denuded preparations, relaxations to sodium nitroprusside were not affected by α-GA. Heterocellular gap junctional communication may therefore account for nitric oxide-independent relaxations evoked both by receptor-dependent and -independent mechanisms in rabbit iliac artery. PMID:9776336

Changes in blood volume and response to vaso-active drugs in horizontally casted primates

NASA Technical Reports Server (NTRS)

Dickey, D. T.; Teoh, K. K.; Sandler, H.; Stone, H. L.

1982-01-01

Experiments were performed on horizontally casted primates (male rhesus monkeys) in order to note changes in blood volume caused by horizontal restraint, to compare orthostatic tolerance before and after casting using the responses to upright tilting, to begin to uncover the cardiovascular and neural mechanisms involved in deconditioning, and to compare the data with that obtained from bed-rested human subjects and from humans exposed to weightlessness. Bolus injections of norepinephrine of 2.0 microgram/kg, phenylephrine of 4.0 microgram/kg, and nitroprusside of 2.0 microgram/kg were administered; and aortic pressure and heart rate were recorded during the injections. The results indicate that the horizontally casted primate is a valid animal model for studying the effects of simulated zero-G on the human cardiovascular system.

Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside-induced lipid peroxidation in rat pancreas by water extractable phytochemicals from some tropical spices.

PubMed

Adefegha, Stephen Adeniyi; Oboh, Ganiyu

2012-07-01

Spices have been used as food adjuncts and in folklore for ages. Inhibition of key enzymes (α-amylase and α-glucosidase) involved in the digestion of starch and protection against free radicals and lipid peroxidation in pancreas could be part of the therapeutic approach towards the management of hyperglycemia and dietary phenolics have shown promising potentials. This study investigated and compared the inhibitory properties of aqueous extracts of some tropical spices: Xylopia aethiopica [Dun.] A. Rich (Annonaceae), Monodora myristica (Gaertn.) Dunal (Annonaceae), Syzygium aromaticum [L.] Merr. et Perry (Myrtaceae), Piper guineense Schumach. et Thonn (Piperaceae), Aframomum danielli K. Schum (Zingiberaceae) and Aframomum melegueta (Rosc.) K. Schum (Zingiberaceae) against α-amylase, α-glucosidase, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and sodium nitroprusside (SNP)-induced lipid peroxidation in rat pancreas--in vitro using different spectrophotometric method. Aqueous extract of the spices was prepared and the ability of the spice extracts to inhibit α-amylase, α-glucosidase, DPPH radicals and SNP-induced lipid peroxidation in rat pancreas--in vitro was investigated using various spectrophotometric methods. All the spice extracts inhibited α-amylase (IC(50) = 2.81-4.83 mg/mL), α-glucosidase (IC(50) = 2.02-3.52 mg/mL), DPPH radicals (EC(50) = 15.47-17.38 mg/mL) and SNP-induced lipid peroxidation (14.17-94.38%), with the highest α-amylase & α-glucosidase inhibitory actions and DPPH radical scavenging ability exhibited by X. aethiopica, A. danielli and S. aromaticum, respectively. Also, the spices possess high total phenol (0.88-1.3 mg/mL) and flavonoid (0.24-0.52 mg/mL) contents with A. melegueta having the highest total phenolic and flavonoid contents. The inhibitory effects of the spice extracts on α-amylase, α-glucosidase, DPPH radicals and SNP-induced lipid peroxidation in pancreas (in vitro) could be attributed to the presence of biologically active phytochemicals such as phenolics and some non-phenolic constituents of the spices. Furthermore, these spices may exert their anti-diabetic properties through the mechanism of enzyme inhibition, free radicals scavenging ability and prevention of lipid peroxidation.

Exogenous sodium nitroprusside and glutathione alleviate copper toxicity by reducing copper uptake and oxidative damage in rice (Oryza sativa L.) seedlings.

PubMed

Mostofa, Mohammad Golam; Seraj, Zeba Islam; Fujita, Masayuki

2014-11-01

Nitric oxide (NO) and glutathione (GSH) regulate a variety of physiological processes and stress responses; however, their involvement in mitigating Cu toxicity in plants has not been extensively studied. This study investigated the interactive effect of exogenous sodium nitroprusside (SNP) and GSH on Cu homeostasis and Cu-induced oxidative damage in rice seedlings. Hydroponically grown 12-day-old seedlings were subjected to 100 μM CuSO4 alone and in combination with 200 μM SNP (an NO donor) and 200 μM GSH. Cu exposure for 48 h resulted in toxicity symptoms such as stunted growth, chlorosis, and rolling in leaves. Cu toxicity was also manifested by a sharp increase in lipoxygenase (LOX) activity, lipid peroxidation (MDA), hydrogen peroxide (H2O2), proline (Pro) content, and rapid reductions in biomass, chlorophyll (Chl), and relative water content (RWC). Cu-caused oxidative stress was evident by overaccumulation of reactive oxygen species (ROS; superoxide (O2 (•-)) and H2O2). Ascorbate (AsA) content decreased while GSH and phytochelatin (PC) content increased significantly in Cu-stressed seedlings. Exogenous SNP, GSH, or SNP + GSH decreased toxicity symptoms and diminished a Cu-induced increase in LOX activity, O2 (•-), H2O2, MDA, and Pro content. They also counteracted a Cu-induced increase in superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascorbate reductase (MDHAR), and glyoxalase I and glyoxalase II activities, which paralleled changes in ROS and MDA levels. These seedlings also showed a significant increase in catalase (CAT), glutathione peroxidase (GPX), dehydroascorbate reductase (DHAR), glutathione S-transferase (GST) activities, and AsA and PC content compared with the seedlings stressed with Cu alone. Cu analysis revealed that SNP and GSH restricted the accumulation of Cu in the roots and leaves of Cu-stressed seedlings. Our results suggest that Cu exposure provoked an oxidative burden while reduced Cu uptake and modulating the antioxidant defense and glyoxalase systems by adding SNP and GSH play an important role in alleviating Cu toxicity. Furthermore, the protective action of GSH and SNP + GSH was more efficient than SNP alone.

Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy

We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOSmore » and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced vascular dysfunction. • Arsenic reduced ACh-induced aortic relaxation but didn’t alter response to SNP and PE. • Arsenic affected aortic NO signalling and production of inflammatory mediators. • Arsenic produced vasculopathic lesions in aorta. • Atorvastatin restored arsenic-induced functional, biochemical and structural changes.« less

Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions

PubMed Central

2010-01-01

Background Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions. Objectives To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures. Methods In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 μg/m3) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions. Measurements and Main Results Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05). Conclusion Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel exhaust properties, whereas the novel calcium flux-related effect may be associated with exhaust properties more specific for the ETC condition, for example a higher content of diesel soot particles along with their adsorbed organic compounds. PMID:20653945

Responses of aortic depressor nerve-evoked neurones in rat nucleus of the solitary tract to changes in blood pressure

PubMed Central

Zhang, Jing; Mifflin, Steven W

2000-01-01

Using electrophysiological techniques, the discharge of neurones in the nucleus of the solitary tract (NTS) receiving aortic depressor nerve (ADN) inputs was examined during blood pressure changes induced by I.V. phenylephrine or nitroprusside in anaesthetized, paralysed and artificially ventilated rats. Various changes in discharge rate were observed during phenylephrine-induced blood pressure elevations: an increase (n = 38), a decrease (n = 5), an increase followed by a decrease (n = 4) and no response (n = 11). In cells receiving a monosynaptic ADN input (MSNs), the peak discharge frequency response was correlated to the rate of increase in mean arterial pressure (P < 0.01) but was not correlated to the absolute increase in blood pressure. The peak discharge frequency response of cells receiving a polysynaptic ADN input (PSNs) was correlated to neither the absolute increase in blood pressure nor the rate of increase in mean arterial pressure. Diverse changes in discharge rate were observed during nitroprusside-induced reductions in blood pressure: an increase (n = 3), a decrease (n = 10), an increase followed by a decrease (n = 3) and no response (n = 6). Reductions in pressure of 64 ± 2 mmHg produced weak reductions in spontaneous discharge of 1.3 ± 0.9 Hz and only totally abolished spontaneous discharge in one neurone. These response patterns of NTS neurones during changes in arterial pressure suggest that baroreceptor inputs are integrated differently in MSNs compared to PSNs. The sensitivity of MSNs to the rate of change of pressure provides a mechanism for the rapid regulation of cardiovascular function. The lack of sensitivity to the mean level of a pressure increase in both MSNs and PSNs suggests that steady-state changes in pressure are encoded by the number of active neurones and not graded changes in the discharge of individual neurones. Both MSNs and PSNs receive tonic excitatory inputs from the arterial baroreceptors; however, these tonic inputs appear to be insufficient to totally account for their spontaneous discharge. PMID:11101652

Effects of aging and exercise training on spinotrapezius muscle microvascular Po2 dynamics and vasomotor control

PubMed Central

McCullough, Danielle J.; Davis, Robert T.; Dominguez, James M.; Stabley, John N.; Bruells, Christian S.

2011-01-01

With advancing age, there is a reduction in exercise tolerance, resulting, in part, from a perturbed ability to match O2 delivery to uptake within skeletal muscle. In the spinotrapezius muscle (which is not recruited during incline treadmill running) of aged rats, we tested the hypotheses that exercise training will 1) improve the matching of O2 delivery to O2 uptake, evidenced through improved microvascular Po2 (PmO2), at rest and throughout the contractions transient; and 2) enhance endothelium-dependent vasodilation in first-order arterioles. Young (Y, ∼6 mo) and aged (O, >24 mo) Fischer 344 rats were assigned to control sedentary (YSED; n = 16, and OSED; n = 15) or exercise-trained (YET; n = 14, and OET; n = 13) groups. Spinotrapezius blood flow (via radiolabeled microspheres) was measured at rest and during exercise. Phosphorescence quenching was used to quantify PmO2 in vivo at rest and across the rest-to-twitch contraction (1 Hz, 5 min) transition in the spinotrapezius muscle. In a follow-up study, vasomotor responses to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) stimuli were investigated in vitro. Blood flow to the spinotrapezius did not increase above resting values during exercise in either young or aged groups. Exercise training increased the precontraction baseline PmO2 (OET 37.5 ± 3.9 vs. OSED 24.7 ± 3.6 Torr, P < 0.05); the end-contracting PmO2 and the time-delay before PmO2 fell in the aged group but did not affect these values in the young. Exercise training improved maximal vasodilation in aged rats to acetylcholine (OET 62 ± 16 vs. OSED 27 ± 16%) and to sodium nitroprusside in both young and aged rats. Endurance training of aged rats enhances the PmO2 in a nonrecruited skeletal muscle and is associated with improved vascular smooth muscle function. These data support the notion that improvements in vascular function with exercise training are not isolated to the recruited muscle. PMID:21212242

Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside.

PubMed

Chantler, Paul D; Nussbacher, Amit; Gerstenblith, Gary; Schulman, Steven P; Becker, Lewis C; Ferrucci, Luigi; Fleg, Jerome L; Lakatta, Edward G; Najjar, Samer S

2011-05-01

The coupling between arterial elastance (E(A); net afterload) and left ventricular elastance (E(LV); pump performance), known as E(A)/E(LV), is a key determinant of cardiovascular performance and shifts during exercise due to a greater increase in E(LV) versus E(A). This normal exercise-induced reduction in E(A)/E(LV) decreases with advancing age. We hypothesized that sodium nitroprusside (SNP) can acutely ameliorate the age-associated deficits in E(A)/E(LV). At rest and during graded exercise to exhaustion, E(A) was characterized as end-systolic pressure/stroke volume and E(LV) as end-systolic pressure/end-systolic volume. Resting E(A)/E(LV) did not differ between old (70 ± 8 yr, n = 15) and young (30 ± 5 yr, n = 17) subjects because of a tandem increase in E(A) and E(LV) in older subjects. During peak exercise, a blunted increase in E(LV) in old (7.8 ± 3.1 mmHg/ml) versus young (11.4 ± 6.5 mmHg/ml) subjects blunted the normal exercise-induced decline in E(A)/E(LV) in old (0.25 ± 0.11) versus young (0.16 ± 0.05) subjects. SNP administration to older subjects lowered resting E(A)/E(LV) by 31% via a reduction in E(A) (10%) and an increase in E(LV) (47%) and lowered peak exercise E(A)/E(LV) (36%) via an increase in E(LV) (68%) without a change in E(A). Importantly, SNP attenuated the age-associated deficits in E(A)/E(LV) and E(LV) during exercise, and at peak exercise E(A)/E(LV) in older subjects on drug administration did not differ from young subjects without drug administration. In conclusion, some age-associated deficiencies in E(A)/E(LV), E(A), and E(LV), in older subjects can be acutely abolished by SNP infusion. This is relevant to common conditions in older subjects associated with a significant impairment of exercise performance such as frailty or heart failure with preserved ejection fraction.

Bcl-2 upregulation and neuroprotection in guinea pig brain following chronic simvastatin treatment.

PubMed

Franke, Cornelia; Nöldner, Michael; Abdel-Kader, Reham; Johnson-Anuna, Leslie N; Gibson Wood, W; Müller, Walter E; Eckert, Gunter P

2007-02-01

The present study determined if chronic simvastatin administration in vivo would provide neuroprotection in brain cells isolated from guinea pigs after challenge with the Bcl-2 inhibitor HA 14-1 or the NO donor sodium nitroprusside (SNP). Bcl-2 levels were significantly increased in brains of simvastatin-treated guinea pigs while levels of the pro-apoptotic protein Bax were significantly reduced. The ratio of Bax/Bcl-2, being a critical factor of the apoptotic state of cells, was significantly reduced in simvastatin-treated animals. Cholesterol levels in the brain remained unchanged in the simvastatin group. Brain cells isolated from simvastatin-treated guinea pigs were significantly less vulnerable to mitochondrial dysfunction and caspase-activation. These results provide new insight into potential mechanisms for the protective actions of statins within the CNS where programmed cell death has been implicated.

Possible involvement of nitric oxide in pilocarpine induced seminal emission in rats.

PubMed

Tomé, A R; da Silva, J C; Souza, A A; Mattos, J P; Vale, M R; Rao, V S

1999-12-01

Intraperitoneal injection of pilocarpine (0.75-3.0 mg/kg) caused a dose-related seminal emission in adult male rats. The seminal emission response to 3 mg/kg of pilocarpine was greatly reduced in atropinized (5 and 10 mg/kg, SC) animals, suggesting a cholinomimetic effect. Nw-nitro-L-arginine methyl ester (5, 10, and 20 mg/kg, SC), a nitric oxide synthesis inhibitor, also inhibited the pilocarpine-induced seminal emission, which was reversed by L-arginine (600 mg/kg, SC) or by coinjection of sodium nitroprusside (0.5 mg/kg, SC). Urine analysis for levels of nitric oxide metabolites, nitrate/nitrite (NO3-/NO2-), showed marked alterations in accordance with the drug treatments. The results suggest that nitric oxide mediates the inhibitory neurotransmission responsible for seminal emission in pilocarpine stimulated rats.

A Simple and Useful Method to Apply Exogenous NO Gas to Plant Systems: Bell Pepper Fruits as a Model.

PubMed

Palma, José M; Ruiz, Carmelo; Corpas, Francisco J

2018-01-01

Nitric oxide (NO) is involved many physiological plant processes, including germination, growth and development of roots, flower setting and development, senescence, and fruit ripening. In the latter physiological process, NO has been reported to play an opposite role to ethylene. Thus, treatment of fruits with NO may lead to delay ripening independently of whether they are climacteric or nonclimacteric. In many cases different methods have been reported to apply NO to plant systems involving sodium nitroprusside, NONOates, DETANO, or GSNO to investigate physiological and molecular consequences. In this chapter a method to treat plant materials with NO is provided using bell pepper fruits as a model. This method is cheap, free of side effects, and easy to apply since it only requires common chemicals and tools available in any biology laboratory.

Comparison of inert-gas-fusion and modified Kjeldahl techniques for determination of nitrogen in niobium alloys

NASA Technical Reports Server (NTRS)

Merkle, E. J.; Graab, J. W.; Davis, W. F.

1974-01-01

This report compares results obtained for the determination of nitrogen in a selected group of niobium-base alloys by the inert-gas-fusion and the Kjeldahl procedures. In the inert-gas-fusion procedure the sample is heated to approximately 2700 C in a helium atmosphere in a single-use graphite crucible. A platinum flux is used to facilitate melting of the sample. The Kjeldahl method consisted of a rapid decomposition with a mixture of hydrofluoric acid, phosphoric acid, and potassium chromate; distillation in the presence of sodium hydroxide; and highly sensitive spectrophotometry with nitroprusside-catalyzed indophenol. In the 30- to 80-ppm range, the relative standard deviation was 5 to 7 percent for the inert-gas-fusion procedure and 2 to 8 percent for the Kjeldahl procedure. The agreement of the nitrogen results obtained by the two techniques is considered satisfactory.

[Activation of the bioluminescence of the sensor Escherichia coli strains used for detecting N-acyl-homoserine lactones in the presence of nitrofurans and NO generators].

PubMed

Zaĭtseva, Iu V; Granik, V G; Belik, A S; Koksharova, O A; Khmel', I A

2010-01-01

Nitrofurans (nitrofurazone, nitrofurantoin, furazidin, nifuroxazide), and nitric oxide generators (sodium nitroprusside and isosorbide mononitrate) in subinhibitory concentrations were shown to significantly increase the bioluminescence of the sensor Escherichia coli strains used for detecting N-acyl-homoserine lactones, signaling molecules of Quorum Sensing (QS) regulatory systems. The highest activation of bioluminescence (up to 250-400 fold) was observed in the presence of nitrofurazone on E. coli DH5alpha biosensors containing lux-reporter plasmids pSB401 or pSB536. However, this activation was not specifically associated with the functioning of QS systems. We suggest that the effect observed results from a direct action of nitrofurans and NO donors on the process of bioluminescence. The data indicate the necessity of using the biosensors that make it possible to detect specific effects of substances tested on QS regulation.

Nitric oxide - an activating factor of adenosine deaminase 2 in vitro.

PubMed

Sargisova, Ye G; Andreasyan, N A; Hayrapetyan, H L; Harutyunyan, H A

2012-01-01

In this study we have investigated the effect of reactive oxygen species produced by some chemicals in aqueous solutions on activity of adenosine deaminase 2 (ADA2) purified from human blood plasma. An activating effect on ADA2 was observed in vitro with sodium nitroprusside (SNP), the source of NO (nitrosonium ions NO(-) in aqueous solutions). Not SH-groups of cysteine but other amino acid residues sensitive to NO were responsible for ADA2 activation. The SNP-derived activation was more pronounced when purified ADA2 was preincubated with heparin and different proteins as an experimental model of the protein environment in vivo. The most effective was heparin, which is known for its ability to regulate enzyme and protein functions in extracellular matrix. We conclude that ADA2 is a protein with flexible conformation that is affected by the protein environment, and it changes its activity under oxidative (nitrosative) stress.

Alterations in Skeletal Muscle Microcirculation of Head-Down Tilted Rats

NASA Technical Reports Server (NTRS)

Musacchia, X. J.; Stepke, Bernhard; Fleming, John T.; Joshua, Irving G.

1992-01-01

In this study we assessed the function of microscopic blood vessels in skeletal muscle (cremaster muscle) for alterations which may contribute to the observed elevation of blood pressure associated with head-down tilted whole body suspension (HDT/WBS), a model of weightlessness. Arteriolar baseline diameters, vasoconstrictor responses to norepinephrine (NE) and vasodilation to nitroprusside (NP) were assessed in control rats, rats suspended for 7 or 14 day HDT/WBS rats, and rats allowed to recover for 1 day after 7 days HDT/WBS. Neither baseline diameters nor ability to dilate were influenced by HDT/WBS. Maximum vasoconstriction to norepinephrine was significantly greater in arterioles of hypertensive 14 day HDT/WBS rats. This first study of the intact microvasculature in skeletal muscle indicates that an elevated contractility of arterioles to norepinephrine in suspended rats, and suggests an elevated peripheral resistance in striated muscle may contribute to the increase in blood pressures among animals subjected to HDT/WBS.

Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats.

PubMed

Capellini, Verena Kise; Baldo, Caroline Floreoto; Celotto, Andréa Carla; Batalhão, Marcelo Eduardo; Cárnio, Evelin Capellari; Rodrigues, Alfredo José; Evora, Paulo Roberto Barbosa

2010-08-01

To verify if an experimental model of alloxan-diabetic rats promotes oxidative stress, reduces nitric oxide bioavailability and causes vascular dysfunction, and to evaluate the effect of N-acetylcysteine (NAC) on these parameters. Alloxan-diabetic rats were treated or not with NAC for four weeks. Plasmatic levels of malondialdehyde (MDA) and nitrite/nitrate (NOx), the endothelial and inducible nitric oxide synthase (eNOS and iNOS) immunostaining and the vascular reactivity of aorta were compared among diabetic (D), treated diabetic (TD) and control (C) rats. MDA levels increased in D and TD. NOx levels did not differ among groups. Endothelial eNOS immunostaining reduced and adventitial iNOS increased in D and TD. The responsiveness of rings to acetylcholine, sodium nitroprusside, and phenylephrine did not differ among groups. NAC had no effect on the evaluated parameters and this experimental model did not promote vascular dysfunction despite the development of oxidative stress.

Role of catecholamines and nitric oxide on pigment displacement of the chromatophores of freshwater snakehead teleost fish, Channa punctatus.

PubMed

Biswas, Saikat P; Jadhao, Arun G; Palande, Nikhil V

2014-04-01

We are reporting for the first time that the catecholamines (adrenaline and noradrenaline) inhibit the effect of nitric oxide (NO) on melanosome dispersion in freshly isolated scales of the freshwater snakehead fish, Channa punctatus. We studied the effect of NO and catecholamines on the pigment displacement by observing the changes in the melanophore index. The scales when treated with solution containing NO donor sodium nitroprusside (SNP) showed dispersion of melanosomes, whereas NO synthase blocker N-omega-Nitro-L-arginine suppresses this action of SNP. Treatment with adrenaline and noradrenaline on the isolated scales caused aggregation of melanosomes. Scales treated with solution containing catecholamines and SNP resulted in aggregation of melanosomes suggesting that catecholamines mask the effect of SNP. These results suggest that the catecholamines are inhibiting the effect of NO and causing the aggregation of the melanosomes may be via surface receptors.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watson, E.L.; Singh, J.C.; Jacobson, K.L.

Cholinergic-mediated amylase release in mouse parotid acini was augmented by forskolin; the potency but not the maximal response to carbachol was altered. Amylase released by carbachol plus forskolin was dependent on extracellular calcium and was mimicked by the calcium ionophore, A23187 plus forskolin. Forskolin was also shown to enhance carbachol-stimulated /sup 45/Ca/sup 2 +/ uptake into isolated acini. Hydroxylamine, nitroprusside, and 8-bromo-c-GMP each in combination with forskolin mimicked the effects of carbachol plus forskolin on amylase release. In the presence of carbachol (10/sup -8/M) forskolin did not augment c-AMP levels. However, in the presence of carbachol (5 x 10/sup -7/more » M) or hydroxylamine (50 ..mu..M) forskolin did significantly augment c-AMP accumulation. These results suggest that calcium and c-GMP may mediate the augmentation of cholinergic-mediated amylase release by effects on c-AMP metabolism. 21 references, 1 figure, 3 tables.« less

Effects of papaverine on carbachol- and high K+ -induced contraction in the bovine abomasum.

PubMed

Kaneda, Takeharu; Saito, Erika; Kanda, Hidenori; Urakawa, Norimoto; Shimizu, Kazumasa

2015-10-01

The effects of papaverine on carbachol (CCh) -and high K(+)- induced contraction in the bovine abomasum were investigated. Papaverine inhibited CCh (1 µM) -and KCl (65 mM) -induced contractions in a concentration-dependent manner. Forskolin or sodium nitroprusside inhibited CCh-induced contractions in a concentration-dependent manner in association with increases in the cAMP or cGMP contents, whereas papaverine increased cGMP contents only at 30 µM. Changes in the extracellular Ca(2+) from 1.5 mM to 7.5 mM reduced verapamil-induced relaxation in high K(+)-depolarized muscles, but papaverine-induced relaxation did not change. Furthermore, papaverine (30 µM) and NaCN (300 µM) decreased the creatine phosphate contents. These results suggest that the relaxing effects of papaverine on the bovine abomasum are mainly due to the inhibition of aerobic energy metabolism.

Influence of the nature of the ligand on the structure and spectra of boron-containing iron(II) dioximates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pol'shin, E.V.; Trachevskii, V.V.; Tyukhtenko, S.I.

1987-11-01

The Moessbauer (/sup 57/Fe) and NMR (/sup 1/H, /sup 13/C, /sup 11/B) spectra of the macrobicyclic dioximates FeD/sub 3/(BF)/sub 2/, where H/sub 2/D stands for glyoxime, methylglyoxime, 1,2-cyclohexanedione dioxime (Nioxime), furildioxime, and benzil dioxime, have been investigated. The values of the isomer shifts for these compounds range from 0.31 to 0.37 mm/sec relative to sodium nitroprusside, and the Raman scattering ranges from 0.6 to 0.9 for the aliphatic oximes and is equal to approx. 0.2 for the aromatic oximes. The changes in the Raman scattering have been related to the angle of distortion of the trigonal prism. The greatest changesmore » in the /sup 13/C and /sup 1/H NMR spectra are observed for the atoms of the substituents.« less

Hypertensive crisis in children.

PubMed

Chandar, Jayanthi; Zilleruelo, Gastón

2012-05-01

Hypertensive crisis is rare in children and is usually secondary to an underlying disease. There is strong evidence that the renin-angiotensin system plays an important role in the genesis of hypertensive crisis. An important principle in the management of children with hypertensive crisis is to determine if severe hypertension is chronic, acute, or acute-on-chronic. When it is associated with signs of end-organ damage such as encephalopathy, congestive cardiac failure or renal failure, there is an emergent need to lower blood pressures to 25-30% of the original value and then accomplish a gradual reduction in blood pressure. Precipitous drops in blood pressure can result in impairment of perfusion of vital organs. Medications commonly used to treat hypertensive crisis in children are nicardipine, labetalol and sodium nitroprusside. In this review, we discuss the pathophysiology, differential diagnosis and recent developments in management of hypertensive crisis in children.

Responses of enzymatically isolated mammalian vascular smooth muscle cells to pharmacological and electrical stimuli.

PubMed

DeFeo, T T; Morgan, K G

1985-05-01

A modified method for enzymatically isolating mammalian vascular smooth muscle cells has been developed and tested for ferret portal vein smooth muscle. This method produces a high proportion of fully relaxed cells and these cells appear to have normal pharmacological responsiveness. The ED50 values for both alpha stimulation and potassium depolarization are not significantly different in the isolated cells from those obtained from intact strips of ferret portal vein, suggesting that the enzymatic treatment does not destroy receptors or alter the electrical responsiveness of the cells. It was also possible to demonstrate a vasodilatory action of papaverine, nitroprusside and adenosine directly on the isolated cells indicating that the pathways involved are intact in the isolated cells. This method should be of considerable usefulness, particularly in combination with the new fluorescent indicators and cell sorter techniques which require isolated cells.

Relaxant effects of butylidenephthalide in isolated dog blood vessels.

PubMed

Ko, Wun Chang; Liao, Chao-Chiun; Shih, Chih-Hsien; Lei, Chien-Bang; Chen, Chi-Ming

2002-11-01

We investigated the reason why butylidenephthalide (Bdph) can have an antianginal effect without changing blood pressure in conscious rats. Isolated dog coronary artery (CA), femoral vein (FV), femoral artery (FA), and mesenteric artery (MA) were used to evaluate the relaxant effects of Bdph. Bdph concentration-dependently relaxed isolated CA, FV, FA, and MA precontracted by KCl (60 mM) and phenylephrine (phe, 5 microM) with the exception that CA was precontracted by prostaglandin F 2 alpha (PGF 2 alpha, 2 microM) instead of phe. The potency order of Bdph to these blood vessels was FV > CA > FA > or = MA. Bdph also concentration-dependently and non-competitively inhibited cumulative KCl (5 - 120 mM)- and phe (0.1 - 100 microM)-induced contractions in normal, and inhibited cumulative Ca 2+-induced contractions in depolarized blood vessels. The potency order of Bdph to these blood vessels was FV congruent with CA > FA congruent with MA. Bdph (0.02 - 0.04 mM) concentration-dependently and leftward-shifted the log concentration-response curves in parallel and significantly increased the pD 2 value of forskolin, but not nitroprusside in FV. Bdph (0.1 mM) did both in CA. Bdph (0.225 - 0.45 mM) did the opposite to that of nitroprusside, but not forskolin, in FA. Bdph (0.45 - 0.9 mM) did neither in MA. Bdph (0.1 - 1 mM) significantly inhibited cAMP- but not cGMP-PDE activities in these four blood vessels, suggesting that Bdph more selectively inhibited the former in these tissues. The above results suggest that the higher potencies of Bdph on FV and CA than on FA and MA, may be interpreted as the reason why Bdph is useful in the treatment of angina pectoris without changing blood pressure, after Bdph administration in vivo, because the venoreturn may be reduced and the coronary flow may be increased without affecting the arterioles, such as MA, the main determinant of blood pressure. Abbreviations. Bdph:butylidenephthalide Phe:phenylephrine PGF 2alpha :prostaglandin F 2alpha CA:coronary artery FV:femoral vein FA:femoral artery MA:mesenteric artery cAMP:adenosine 3',5'-cyclic monophosphate cGMP:guanosine 3',5'-cyclic monophosphate PDE:phosphodiesterase

Protection by scoparone against the alterations of plasma lipoproteins, vascular morphology and vascular reactivity in hyperlipidaemic diabetic rabbit.

PubMed

Huang, H C; Weng, Y I; Lee, C R; Jan, T R; Chen, Y L; Lee, Y T

1993-12-01

1. The in vivo pharmacological effects of scoparone (6,7-dimethoxycoumarin) in a hyperlipidaemic diabetic rabbit model were investigated. 2. Three groups of rabbits were studied: (1) normal, (2) hyperlipidaemic and diabetic-untreated and (3) hyperlipidaemic and diabetic-scoparone treated. The hyperlipidaemic diabetic rabbits were fed with 1% cholesterol and treated with alloxan, a diabetogenic agent. The plasma levels of total cholesterol, total triglyceride, very low-density lipoprotein (VLDL) cholesterol, low density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were markedly increased as soon as the rabbit became diabetic at the second week. Scoparone-treatment (5 mg kg-1 day-1, s.c.) significantly reduced the plasma lipid and lipoprotein cholesterol levels of the hyperlipidaemic diabetic rabbit to 73.3% of total cholesterol, 48.3% of total triglyceride, 66.0% of VLDL cholesterol, 55.7% of LDL cholesterol and 79.5% of HDL cholesterol. 3. Six weeks after cholesterol-feeding, the aortic arch and thoracic aorta were dissected for morphological and functional studies. In vascular rings from the untreated hyperlipidaemic diabetic rabbit, there was intimal thickening with accumulation of fatty streaks, foam cells and migration of smooth muscle cells to the intima. In the rabbits treated with scoparone, there were fewer pathological morphology changes found in vascular segments than in the untreated hyperlipidaemic diabetic rabbits. 4. In the vascular reactivity experiments, the phenylephrine-induced contraction and nitroprusside induced dilatation did not differ significantly among the three rabbit groups, except that the contraction was enhanced in the thoracic aorta of hyperlipidaemic diabetic rabbits either untreated or treated withscoparone, as compared to the normal group, and the sensitivity to nitroprusside was increased in the thoracic aorta of the scoparone-treated group as compared to the untreated group.5. The endothelium-dependent dilatation induced by acetylcholine was significantly attenuated in both the aortic arch and thoracic aorta from the hyperlipidaemic diabetic rabbits as compared to the normal rabbits. This attenuation was partially prevented, when scoparone (5 mg kg-1) was administered daily.6. These results suggest that scoparone protects against some alterations of plasma lipoproteins,vascular morphology and vascular reactivity in the hyperlipidaemic diabetic rabbit. These protective effects of scoparone may be partly related to its free radical scavenging property.

In vivo cardiac electrical activity of nitric oxide in barium chloride treated male rats

NASA Astrophysics Data System (ADS)

Salihi, Abbas B. Q.; Shekha, Mudhir S.; Hamadamin, Peshraw S.; Maulood, Ismail M.; Rasul, Khder H.; Salim, Muhammed A.; Qadir, Fikry A.; Othman, Goran Q.; Mahmud, Almas M. R.; Al-Habib, Omar A. M.

2017-09-01

The aim of this study was to evaluate the effects of nitric oxide in barium chloride (BaCl2)-induced arrhythmia in male albino rats. 10mg/kg/hr of BaCl2 was infused intravenously through caudal vein to induce arrhythmia, to ameliorate this effect 1mg and 10mg/kg/hr of sodium nitroprusside (SNP; nitric oxide donor) were infused, respectively. The ECG signals and parameters were recorded and analyzed with the aid of BioAmp of ADInstruments data acquisition system and Labchart software. The results showed that infusion of both 1mg/kg/hr and 10mg/kg/hr of SNP non significantly changed heart rate (BPM), QRS interval (s), S amplitude (mV), T amplitude (mV), ST height (mV), JT height (mV), QT intervals (s) and QTc (s). In conclusion the results of the current study indicate that SNP cannot ameliorate arrhythmia-induced by BaCl2.

[A clinical study and analysis of congenital lenticular dislocation (35 cases)].

PubMed

Guo, X; Mao, W; Chen, Y; Ma, Q; Zeng, L; Luo, T

1991-12-01

Thirty-five cases of congenital lenticular dislocation seen in our Center since 1985 have been studied and analyzed clinically. By the survey of pedigrees and examination of these patients, including ocular, systemic, skeletal X-ray, psychocardiogram, and urinary sodium-nitroprusside test, 21 cases were diagnosed as Marfan's syndrome, 6 cases as simple ectopia lentis, 3 cases as Weill-Marchesani's syndrome, 4 cases as aniridia and 1 case as homecys tinuria. We found that the most significant ocular manifestation of congenital lenticular dislocation was reduction in visual acuity. The severity of visual disturbance varied with the types of dislocation and the visual deficiency was closely related to the intermediate-grade (II) dislocation of the lens. Examination of ERG showed normal function in most of the patients. From this, we believe that the major cause of visual reduction in congenital lenticular dislocation is lenticular myopia and astigmatism. There fore, early diagnosis and effective correction of vision should be emphasized to prevent the occurrence of amblyopia.

Effect of hypothyroidism on the nitrergic relaxant responses of corpus cavernosal smooth muscle in rabbits.

PubMed

Sarac, Bulent; Yildirim, Mustafa K; Bagcivan, Ihsan; Kaya, Kemal; Kilicarslan, Hakan; Yildirim, Sahin

2006-01-01

The incidence of hormonal dysfunction as a cause of impotence remains controversial. However, several recent studies have reported evidence of hormonal abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. In the present study, we examined nitrergic responses in hypothyroidism in rabbit corpus cavernosum and compared them with controls. Carbachol-induced relaxation responses and electrical field stimulation (EFS)-induced frequency-dependent relaxations decreased significantly in hypothyroid rabbits. Papaverine and sodium nitroprusside (SNP)-induced relaxation responses did not change significantly in hypothyroid rabbits. The contraction responses of phenylephrine and EFS-induced frequency-dependent contractions were significantly decreased in the hypothyroid group. We can speculate that the reduction of relaxant responses to EFS and carbachol in hypothyroid rabbits can depend on a decreased release of nitric oxide (NO) from nitrergic nerves and endothelium or a reduction of muscarinic receptor density. Also, decreases in contraction responses may depend on diminished adrenoceptor density.

The effect of hypoxia on neuroeffector transmission in the bovine retractor penis and rat anococcygeus muscles.

PubMed Central

Bowman, A.; McGrath, J. C.

1985-01-01

The effects of reducing the PO2 of the bathing fluid were studied on non-adrenergic non-cholinergic (NANC) transmission in isolated preparations of the bovine retractor penis muscle, the rat anococcygeus muscle, the guinea-pig taenia caeci and the guinea-pig urinary bladder. Hypoxia rapidly and reversibly impaired NANC transmission in the bovine retractor penis and rat anococcygeus muscles but did not affect transmission in the guinea-pig taenia caeci or bladder, suggesting that different NANC mechanisms are involved. Although neurally-evoked relaxation of the bovine retractor penis was impaired by hypoxia, relaxations produced by vasoactive intestinal peptide, prostaglandin E1, sodium nitroprusside or an inhibitory factor isolated from the bovine retractor penis were unaffected. Since the inhibitory factor is similar to, and may actually be the NANC transmitter, the results suggest that the site of action of hypoxia in impairing transmission is prejunctional at the inhibitory nerve endings. PMID:2994787

Iron-induced nitric oxide leads to an increase in the expression of ferritin during the senescence of Lotus japonicus nodules.

PubMed

Chungopast, Sirinapa; Duangkhet, Mallika; Tajima, Shigeyuki; Ma, Jian Feng; Nomura, Mika

2017-01-01

Iron is an essential nutrient for legume-rhizobium symbiosis and accumulates abundantly in the nodules. However, the concentration of free iron in the cells is strictly controlled to avoid toxicity. It is known that ferritin accumulates in the cells as an iron storage protein. During nodule senescence, the expression of the ferritin gene, Ljfer1, was induced in Lotus japonicus. We investigated a signal transduction pathway leading to the increase of Ljfer1 in the nodule. The Ljfer1 promoter of L. japonicus contains a conserved Iron-Dependent Regulatory Sequence (IDRS). The expression of Ljfer1 was induced by the application of iron or sodium nitroprusside, which is a nitric oxide (NO) donor. The application of iron to the nodule increased the level of NO. These data strongly suggest that iron-induced NO leads to increased expression of Ljfer1 during the senescence of L. japonicus nodules. Copyright © 2016 Elsevier GmbH. All rights reserved.

A "Dual-acceptor Channel" Membraneless Gas-diffusion Unit for Simultaneous Determination of Ethanol and Acetaldehyde in Liquors Using Reverse Flow Injection.

PubMed

Choengchan, Nathawut; Poontong, Bangerdsuk; Mathaweesansurn, Arjnarong; Maneerat, Noppadol; Motomizu, Shoji; Ratanawimarnwong, Nuanlaor; Nacapricha, Duangjai

2018-01-01

A new design of membraneless gas-diffusion unit with dual acceptor channels for separation, collection and simultaneous determination of two volatile analytes in liquid sample is presented. The unit is comprised of three parallel channels in a closed module. A sample is aspirated into the central channel and two kinds of reagents are introduced into the other two channels. Two analytes are isolated from the sample matrix by diffusion into head-space and absorbed into the specific reagents. Non-absorbed vapor is released by opening the programmable controlled lid. The unit was applied to liquors for measurement of ethanol and acetaldehyde using reverse flow injection. Dichromate and nitroprusside were exploited as reagents for colorimetric detection of ethanol and acetaldehyde, respectively. Good linearity ranges (r 2 >0.99) with high precision (RSD <2%) and high accuracy (recovery: 90 - 105%) were achieved. The results were compared to the results by GC-FID and no significant difference was observed by paired t-test (95% confidence).

Microinjection of l-glutamate into the nucleus ambiguus partially inhibits gastric motility through the NMDA receptor - nitric oxide pathway.

PubMed

Sun, Hong-Zhao; Zhao, Shu-Zhen; Ai, Hong-Bin

2014-06-01

We have previously reported that both l-glutamate (l-Glu) and nitric oxide (NO) modulate gastric motility in the nucleus ambiguus (NA). The aim of this study is to explore the potential correlation between the l-Glu and NO. A latex balloon connected to a pressure transducer was inserted into the pylorus through the fundus of anesthetized male Wistar rats to continuously record changes in gastric smooth muscle contractile curves. Pretreatment with the NO-synthase inhibitor N-nitro-l-arginine methylester (l-NAME) did not completely abolish the inhibitory effect of l-Glu on gastric motility, but intravenous injection of the ganglionic blocker hexamethonium bromide (Hb) did. By using a specific N-methyl-d-aspartic acid (NMDA) receptor antagonist, we blocked the inhibitory effect of the NO-donor sodium nitroprusside (SNP) on gastric motility. These results suggest that microinjections of l-Glu into the NA inhibits gastric motility by activating the cholinergic preganglionic neurons, partially through the NMDA receptor - NO pathway.

Role of nitric oxide in the control of the gastric motility within the nucleus ambiguus of rats.

PubMed

Sun, H-Z; Zhao, S-Z; Ai, H-B

2012-12-01

This study aims to investigate whether exogenous nitric oxide (NO) plays a role in controlling gastric motility within the nucleus ambiguus (NA). Experiments were performed on male Wistar rats anaesthetized with chloral hydrate. A latex balloon, connected to a pressure transducer, was inserted into the pylorus through the fundus for continuous recording of the change of gastric smooth muscle contractile curves. Microinjection of the NO-donor sodium nitroprusside (SNP; 5 nmol) or L-arginine (L-Arg; 5 nmol) into the NA significantly inhibited gastric motility, whereas the treatment of NO-synthase inhibitor N-nitro-L-arginine methylester (L-NAME) increased gastric motility remarkably. The negative effect of SNP or L-Arg on gastric motility was abolished by bilateral subdiaphragmatic vagotomy as well as by intravenous injection of ganglionic blocker, hexamethonium bromide (Hb). These results demonstrated that NO inhibited gastric motility by activating the cholinergic preganglionic neurons in the NA and through the mediation of vagus nerves.

Exogenous Nitric Oxide (NO) Interferes with Lead (Pb)-Induced Toxicity by Detoxifying Reactive Oxygen Species in Hydroponically Grown Wheat (Triticum aestivum) Roots

PubMed Central

Kaur, Gurpreet; Singh, Harminder Pal; Batish, Daizy R.; Mahajan, Priyanka; Kohli, Ravinder Kumar; Rishi, Valbha

2015-01-01

Nitric Oxide (NO) is a bioactive signaling molecule that mediates a variety of biotic and abiotic stresses. The present study investigated the role of NO (as SNP [sodium nitroprusside]) in ameliorating lead (Pb)-toxicity in Triticum aestivum (wheat) roots. Pb (50 and 250 μM) alone and in combination with SNP (100 μM) was given to hydroponically grown wheat roots for a period of 0–8 h. NO supplementation reduced the accumulation of oxidative stress markers (malondialdehyde, conjugated dienes, hydroxyl ions and superoxide anion) and decreased the antioxidant enzyme activity in wheat roots particularly up to 6 h, thereby suggesting its role as an antioxidant. NO ameliorated Pb-induced membrane damage in wheat roots as evidenced by decreased ion-leakage and in situ histochemical localization. Pb-exposure significantly decreased in vivo NO level. The study concludes that exogenous NO partially ameliorates Pb-toxicity, but could not restore the plant growth on prolonged Pb-exposure. PMID:26402793

Mechanisms of adaptation to nitrosative stress in Bacillus subtilis.

PubMed

Rogstam, Annika; Larsson, Jonas T; Kjelgaard, Peter; von Wachenfeldt, Claes

2007-04-01

Bacteria use a number of mechanisms for coping with the toxic effects exerted by nitric oxide (NO) and its derivatives. Here we show that the flavohemoglobin encoded by the hmp gene has a vital role in an adaptive response to protect the soil bacterium Bacillus subtilis from nitrosative stress. We further show that nitrosative stress induced by the nitrosonium cation donor sodium nitroprusside (SNP) leads to deactivation of the transcriptional repressor NsrR, resulting in derepression of hmp. Nitrosative stress induces the sigma B-controlled general stress regulon. However, a sigB null mutant did not show increased sensitivity to SNP, suggesting that the sigma B-dependent stress proteins are involved in a nonspecific protection against stress whereas the Hmp flavohemoglobin plays a central role in detoxification. Mutations in the yjbIH operon, which encodes a truncated hemoglobin (YjbI) and a predicted 34-kDa cytosolic protein of unknown function (YjbH), rendered B. subtilis hypersensitive to SNP, suggesting roles in nitrosative stress management.

Different responses of mesenteric artery from normotensive and spontaneously hypertensive rats to nitric oxide and its redox congeners.

PubMed

Orescanin, Zorana S; Milovanović, Slobodan R; Spasić, Snezana D; Jones, David R; Spasić, Mihajlo B

2007-01-01

The conversion of nitric oxide (NO*) into its congeners nitrosonium (NO(+)) and nitroxyl (HNO/NO(-)) ions may have important consequences for signal transduction and physiological responses. Manganese-containing superoxide dismutase (MnSOD) may convert NO. into its redox congeners. In our current work, we have examined the mechanism of sodium nitroprusside (SNP)-induced relaxation of arteries, with or without endothelium, from both normotensive and spontaneously hypertensive (SH) rats in the absence and presence of MnSOD. SNP induced a greater degree of relaxation in normotensive than in SH rats. MnSOD antagonized SNP-induced relaxation and effect was greater in normotensive than hypertensive rats. However, MnSOD even potentiated SNP-induced relaxation in mesenteric arteries with endothelium from SH rats. Our results indicate that HNO/NO(-)-mediated relaxation is more effective in mesenteric artery smooth muscle from SH rats than from normotensive rats and that vascular dysfunction in SH rats is not solely endothelium-derived but involves changes in vascular smooth muscles.

Mechanisms of Adaptation to Nitrosative Stress in Bacillus subtilis▿ †

PubMed Central

Rogstam, Annika; Larsson, Jonas T.; Kjelgaard, Peter; von Wachenfeldt, Claes

2007-01-01

Bacteria use a number of mechanisms for coping with the toxic effects exerted by nitric oxide (NO) and its derivatives. Here we show that the flavohemoglobin encoded by the hmp gene has a vital role in an adaptive response to protect the soil bacterium Bacillus subtilis from nitrosative stress. We further show that nitrosative stress induced by the nitrosonium cation donor sodium nitroprusside (SNP) leads to deactivation of the transcriptional repressor NsrR, resulting in derepression of hmp. Nitrosative stress induces the sigma B-controlled general stress regulon. However, a sigB null mutant did not show increased sensitivity to SNP, suggesting that the sigma B-dependent stress proteins are involved in a nonspecific protection against stress whereas the Hmp flavohemoglobin plays a central role in detoxification. Mutations in the yjbIH operon, which encodes a truncated hemoglobin (YjbI) and a predicted 34-kDa cytosolic protein of unknown function (YjbH), rendered B. subtilis hypersensitive to SNP, suggesting roles in nitrosative stress management. PMID:17293416

Mechanism of reduction of mitral regurgitation with vasodilator therapy.

PubMed

Yoran, C; Yellin, E L; Becker, R M; Gabbay, S; Frater, R W; Sonnenblick, E H

1979-04-01

Acute mitral regurgitation was produced in six open chest dogs by excising a portion of the anterior valve leaflet. Electromagnetic flow probes were placed in the left atrium around the mitral anulus and in the ascending aorta to determine phasic left ventricular filling volume, regurgitant volume and stroke volume. The systolic pressure gradient was calculated from simultaneously measured high fidelity left atrial and left ventricular pressures. The effective mitral regurgitant orifice area was calculated from Gorlin's hydraulic equation. Infusion of nitroprusside resulted in a significant reduction in mitral regurgitation. No significant change occurred in the systolic pressure gradient between the left ventricle and the left atrium because both peak left ventricular pressure and left atrial pressure were reduced. The reduction of mitral regurgitation was largely due to reduction in the size of the mitral regurgitant orifice. Reduction of ventricular volume rather than the traditional concept of reduction of impedance of left ventricular ejection may explain the effects of vasodilators in reducing mitral regurgitation.

Effects of abscisic acid and nitric oxide on trap formation and trapping of nematodes by the fungus Drechslerella stenobrocha AS6.1.

PubMed

Xu, Ling-Ling; Lai, Yi-Ling; Wang, Lin; Liu, Xing-Zhong

2011-02-01

The in vitro effects of abscisic acid (ABA) and nitric oxide (NO) on the nematode-trapping fungus Drechslerella stenobrocha AS6.1 were examined. The average number of traps (constricting rings) per colony and the percentage of nematodes (Caenorhabditis elegans) trapped were greatly increased by addition of ABA but greatly suppressed by addition of sodium nitroprusside (SNP, an NO donor) to corn meal agar. The suppressive effect of SNP was not negated by addition of an NO synthase competitive inhibitor (l-naphthylacetic acid, L-NNA) or an NO-specific scavenger [2-(4-carboxyphenyl)-4,4, 5,5-tetramethylimidazoline-1-oxyl-3-oxide, cPTIO]. When added without SNP, however, L-NNA and cPTIO caused moderate increases in trap number and trapping. The results indicate that the trap formation and nematode-trapping ability of D. stenobrocha were enhanced by ABA but decreased by exogenous NO. Copyright © 2010 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Effect of diabetes on the cutaneous microcirculation of the feet in patients with intermittent claudication.

PubMed

Klonizakis, M; Manning, G; Lingam, K; Donnelly, R; Yeung, J M C

2015-01-01

To evaluate endothelial-dependent and - independent cutaneous vasodilator responses in the feet of patients with peripheral arterial disease (PAD) with or without Type 2 diabetes. Cutaneous microvascular responses in the dorsum of both lower limbs were measured in the supine position using Laser Doppler Fluximetry combined with iontophoretic administration of endothelial-dependent (acetylcholine, Ach) and -independent (sodium nitroprusside, SNP) vasodilators in diabetic (n = 19) and non diabetic (n = 17) patients with PAD (presenting as unilateral calf intermittent claudication (IC). In patients with diabetes and IC, endothelial-dependent vasodilation was significantly impaired in the symptomatic limb [74 (57,105) vs 68 (24,81) PU, Z =-2.79, p = 0.005] compared to the asymptomatic limb. Patients without diabetes showed no impairment of vasodilation. Resting ankle-brachial pressure index did not identify the presence of abnormalities in microvascular function. The combination of diabetes and PAD is associated with a reduction in endothelial-dependent cutaneous vasodilation in the feet without an associated reduction in endothelial independent vasodilation.

Ocular hemodynamic effects of nitrovasodilators in healthy subjects.

PubMed

Schmidl, D; Polska, E; Kiss, B; Sacu, S; Garhofer, G; Schmetterer, L

2010-01-01

Nitric oxide (NO) plays a key role in the regulation of ocular blood flow and may be an interesting therapeutic target in ocular ischemic disease. In the present study, we hypothesized that NO-releasing drugs may increase blood flow to the head of the optic nerve and also in the choroid. The study employed a randomized, placebo-controlled, double blind, four-way crossover design. On separate study days, 12 healthy subjects received infusions of nitroglycerin, isosorbide dinitrate, sodium nitroprusside, or placebo. All three study drugs reduced the mean arterial pressure (MAP) and ocular perfusion pressure (OPP) (P < 0.001). None of the administered drugs increased the ocular hemodynamic variables. By contrast, vascular resistance decreased dose dependently during administration of the study drugs (P < 0.001). These results indicate that systemic administration of NO-donor drugs is associated with a decrease in vascular resistance in the ocular vasculature. However, because these drugs also reduce blood pressure, they do not improve perfusion to the posterior eye pole.

Effects of isradipine and other calcium antagonists on arteriovenous-shunt flow in anesthetized rabbits and cats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hof, R.P.

The effects of vasodilators on arteriovenous (AV)-shunt flow was investigated in anesthetized cats and rabbits, using the tracer microsphere method. In cats, the calcium antagonist isradipine reduced AV-shunt flow; verapamil showed a similar tendency and nicardipine was without effect. Dihydralazine strongly increased, but nitroglycerin and dipyridamole decreased AV-shunt flow. In rabbits, the effects of isradipine and verapamil were similar to those seen in cats. Sodium nitroprusside had no effect, whereas prazosin, minoxidil, and the potassium-channel activator cromakalim increased AV-shunt flow. The contrasting effects of drugs sharing the same mechanism of action suggest that target-tissue selectivity is more important than themore » mechanism of action. An increase of AV-shunt flow is unlikely to be beneficial but could be associated with a number of undesirable side effects. It might negatively affect migraine sufferers and, if AV-shunt dilatation shows no tolerance development, it represents an unnecessary hemodynamic burden for the heart.« less

Nitric oxide mitigates arsenic-induced oxidative stress and genotoxicity in Vicia faba L.

PubMed

Shukla, Pratiksha; Singh, A K

2015-09-01

The protective effects of nitric oxide (NO) against arsenic (As)-induced structural disturbances in Vicia faba have been investigated. As treatment (0.25, 0.50, and 1 mM) resulted in a declined growth of V. faba seedlings. Arsenic treatment stimulates the activity of SOD and CAT while the activities of APX and GST content were decreased. The oxidative stress markers such as superoxide radical, hydrogen peroxide and malondialdehyde (lipid peroxidation) contents were enhanced by As. Overall results revealed that significant accumulation of As suppressed growth, photosynthesis, antioxidant enzymes (SOD, CAT, APX, and GST activity), mitotic index, and induction of different chromosomal abnormalities, hence led to oxidative stress. The concentration of SNP (0.02 mM) was very effective in counteracting the adverse effect of As toxicity. These abnormalities use partially or fully reversed by a simultaneous application of As and NO donor and sodium nitroprusside and has an ameliorating effect against As-induced oxidative stress and genotoxicity in V. faba roots.

Skin blood flow responses to the iontophoresis of acetylcholine and sodium nitroprusside in man: possible mechanisms.

PubMed

Morris, S J; Shore, A C

1996-10-15

1. The mechanisms involved in the human skin blood flow responses to iontophoretic application of acetylcholine (ACH; delivered using an anodal charge) or sodium nitroprusside (SNP; administered with a cathodal charge) are unclear. The aims of this study were to investigate possible contributions of prostaglandin production to the increase in skin blood flow induced following the iontophoresis of ACh and to investigate possible contributions from local sensory nerves to the perfusion responses induced by ACh, SNP and their vehicles. 2. The contribution of prostaglandins to the ACh response was determined in a randomized double-blind study of eight healthy subjects, who were studied on two occasions. Basal responses to ACh were measured before the oral administration of 600 mg soluble aspirin in diluted orange juice (1 occasion or orange juice (1 occasion) and again 30 min after the drink. The contribution of local sensory nerve activation to the responses to ACh and ACh vehicle (8 subjects) and to SNP and SNP vehicle (7 subjects) was assessed. EMLA (5%) (a eutectic mixture of lignocaine and prilocaine) and placebo cream were applied to two separate areas on the forearm in a double-blind randomized manner 2 h before drug responses were measured. In all studies the skin microcirculation responses to iontophoretically applied drug vehicle (1 site) and drug (2 sites) were recorded by laser Doppler perfusion imaging. 3. The increase in forearm skin perfusion (P < 0.001) in response to the iontophoresis of ACh minus the response to ACh vehicle was not significantly different following placebo or aspirin administration. The increase in forearm skin red blood cell flux (P < 0.001) in response to the iontophoresis of ACh minus the response to ACh vehicle was not significantly different at the placebo-compared with the EMLA-treated site. THe small increase in perfusion (P < 0.001) in response to the iontophoresis of ACh vehicle was significantly inhibited at the EMLA-compared with the placebo-treated site (P < 0.05). The marked increase in perfusion (P < 0.001) in response to the iontophoresis of SNP vehicle was significantly inhibited at the EMLA-compared with the placebo-treated site (P < 0.01). 4. These data suggest that in healthy volunteers: (1) mechanisms other than prostaglandin production and local sensory nerve activation may be involved in the increase in skin perfusion observed following the iontophoretic application of ACh; and (2) stimulation of local sensory nerves may be responsible for the increase in tissue perfusion observed following the iontophoretic application of either ACh vehicle or SNP vehicle.

Demonstration of nitric oxide synthase activity in crustacean hemocytes and anti-microbial activity of hemocyte-derived nitric oxide.

PubMed

Yeh, Feng-Ching; Wu, Su-Hua; Lai, Chi-Yung; Lee, Chi-Ying

2006-05-01

We determined the biochemical characteristics of nitric oxide synthase (NOS) in hemocytes of the crayfish Procambarus clarkii and investigated the roles of hemocyte-derived NO in host defense. Biochemical analysis indicated the presence of a Ca2+ -independent NOS activity, which was elevated by lipopolysaccharide (LPS) treatment. When bacteria (Staphylococcus aureus) and hemocytes were co-incubated, adhesion of bacteria to hemocytes was observed. NO donor sodium nitroprusside (SNP) significantly increased the numbers of hemocytes to which bacteria adhered. Similarly, LPS elicited bacterial adhesion and the LPS-induced adhesion was prevented by NOS inhibitor NG-monomethyl-L-arginine (L-NMMA). Finally, plate count assay demonstrated that addition of LPS to the hemocytes/bacteria co-incubation resulted in a significant decrease in bacterial colony forming unit (CFU), and that L-NMMA reversed the decreasing effect of LPS on CFU. The combined results demonstrate the presence of a Ca2+ -independent LPS-inducible NOS activity in crayfish hemocytes and suggest that hemocyte-derived NO is involved in promoting bacterial adhesion to hemocytes and enhancing bactericidal activity of hemocytes.

Cellular glucose-6-phosphate dehydrogenase (G6PD) status modulates the effects of nitric oxide (NO) on human foreskin fibroblasts.

PubMed

Cheng, M L; Ho, H Y; Liang, C M; Chou, Y H; Stern, A; Lu, F J; Chiu, D T

2000-06-23

Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in cellular redox homeostasis, which is crucial for cell survival. In the present study, we found that G6PD status determines the response of cells exposed to nitric oxide (NO) donor. Treatment with NO donor, sodium nitroprusside (SNP), caused apoptosis in G6PD-deficient human foreskin fibroblasts (HFF1), whereas it was growth stimulatory in the normal counterpart (HFF3). Such effects were abolished by NO scavengers like hemoglobin. Ectopic expression of G6PD in HFF1 cells switched the cellular response to NO from apoptosis to growth stimulation. Experiments with 1H-¿1,2,4ŏxadiazolo¿4, 3-aquinoxalin-1-one and 8-bromo-cGMP showed that the effects of NO on HFF1 and HFF3 cells were independent of cGMP signalling pathway. Intriguingly, trolox prevented the SNP-induced apoptosis in HFF1 cells. These data demonstrate that G6PD plays a critical role in regulation of cell growth and survival.

Preparation and characterization of oxybenzone-loaded gelatin microspheres for enhancement of sunscreening efficacy.

PubMed

Patel, M; Jain, Sunil K; Yadav, Awesh K; Gogna, D; Agrawal, G P

2006-01-01

The objective of our present study was to prepare and evaluate gelatin microspheres of oxybenzone to enhance its sunscreening efficacy. The gelatin microspheres of oxybenzone were prepared by emulsion method. Process parameters were analyzed to optimize the formulation. The in vitro drug release study was performed in pH 7.4 using cellulose acetate membrane. Microspheres prepared using oxybenzone:gelatin ratio of 1:6 showed slowest drug release and those prepared with oxybenzone:gelatin ratio of 1:2 showed fastest drug release. The gelatin microspheres of oxybenzone were incorporated in aloe vera gel. Sun exposure method using sodium nitroprusside solution was used for in vitro sunscreen efficacy testing. The formulation C5 containing oxybenzone-bearing gelatin microspheres in aloe vera gel showed best sunscreen efficacy. The formulations were evaluated for skin irritation test in human volunteers, sun protection factor, and minimum erythema dose in albino rats. These studies revealed that the incorporation of sunscreening agent-loaded microspheres into aloe vera gel greatly increased the efficacy of sunscreen formulation more than four times.

Establishment of an efficient plant regeneration culture protocol and achievement of successful genetic transformation in Jatropha curcas L.

PubMed

Liu, Ying; Liu, Guoxuan; Yang, Yali; Niu, Sufang; Yang, Fuguang; Yang, Shaoxia; Tang, Jianian; Chen, Jianping

2017-12-01

An efficient and reproducible protocol is described for shoot-bud regeneration and Agrobacterium tumefaciens-mediated genetic transformation of J. curcas. Treating the explants with high concentrations (5-120 mg/L) of TDZ for short durations (5-80 min) before inoculation culture increased significantly the regeneration frequency and improved the quality of the regenerated buds. The highest shoot-buds induction rate (87.35%) was achieved when petiole explants were treated with 20 mg/L TDZ solution for 20 min and inoculated on hormone-free MS medium for 30 days. Regenerated shoots of 0.5 cm or a little longer were isolated and grafted to seedling stocks of the same species, and then the grafted plantlets were planted on half-strength MS medium containing 0.1 mg/L IBA and 2 mg/L sodium nitroprusside (SNP). This grafting strategy was found to be very effective, to obtain that healthy grafted plantlets ready for acclimatization within 20 days. By the above mentioned protocol and with general Agrobacterium - mediated genetic transformation methods only 65 days were needed to obtain intact transgenic plants.

Determination of nitric oxide mediating intracellular Ca2+ release on neurons based on confocal microscopy imaging

NASA Astrophysics Data System (ADS)

Zheng, Liqin; Wang, Yuhua; He, Yipeng; Zeng, Yixiu; Zhang, Yanding; Xie, Shusen

2014-09-01

The gas NO is a ubiquitous intercellular messenger that modulates a wide range of physiological and pathophysiological functions. But few studies were made to study the role of NO in the Ca2+ release in dorsal root ganglion (DRG) neurons by confocal microscopy. Thus the objective of this study was to assess if NO has a role in Ca2+ signaling in DRG neurons using confocal microscopy combined with special fluorescence probe Fluo-3/AM. A 100 μM concentration of the NO donors (Sodium Nitroprusside, Dihydrate, SNP) and NO synthase inhibitor (NG-Monomethyl-L-arginine, Monoacetate salt, L-NMMA) was used in the study. Results showed that the fluorescence intensity increased rapidly after injecting SNP, which indicated that SNP could enhance intracellular Ca2+ release. And the fluorescence intensity shrank gradually with time and kept at a low level for quite a long period after loading with L-NMMA which indicated that L-NMMA could block intracellular Ca2+ release. All these results demonstrated that NO was involved in the regulation of intracellular Ca2+ release in the DRG neurons.

Targeting cysteine residues of human immunodeficiency virus type 1 protease by reactive free radical species.

PubMed

Basu, A; Sehajpal, P K; Ogiste, J S; Lander, H M

1999-01-01

Nitric oxide (NO) is a naturally occurring free radical with many functions. The oxidized form of NO, the nitrosonium ion, reacts with the thiol group of cysteine residues resulting in their modification to S-nitrosothiols. The human immunodeficiency virus type 1 (HIV-1) protease (HIV-PR) has two cysteine residues that are conserved amongst different viral isolates found in patients with acquired immunodeficiency syndrome (AIDS). In an active dimer, these residues are located near the surface of the protease. We have found that treatment of HIV-PR with different NO congeners results in loss of its proteolytic activity and simultaneous formation of S-nitrosothiols. Sodium nitroprusside inhibited HIV-PR up to 70% and S-nitroso-N-acetylpenicillamine completely inhibited the protease within 5 min of treatment. The pattern of inhibition by NO donors is comparable to its inhibition by N-acetyl pepstatin. Using electrospray ionization-mass spectrometry, we identified the modification of HIV-PR by NO as that of S-nitrosation. Our findings point towards a possible role of NO in mediating resistance to HIV-1 infection.

Inositol uptake in rat aorta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rapoport, R.M.; Van Gorp, C.; Chang, Ki-Churl

1990-01-01

{sup 3}H-inositol uptake into deendothelialized aorta was linear for at least 2 h and was composed of both a saturable, Na{sup +}-dependent, and a nonsaturable, Na{sup +}-independent component. The Na{sup +}-dependent component of inositol uptake had a K{sub m} of 50 {mu}M and a V{sub max} of 289 pmol/mg prot/h. Exposure to LiCl, ouabain, or Ca{sup 2+} - free Krebs-Ringer bicarbonate solution inhibited uptake. Metabolic poisoning with dinitrophenol, as well as incubation with phloretin, an inhibitor of carrier-mediated hexose transport, also inhibited uptake. Exposure to norepinephrine decreased inositol uptake, while phorbol myristate acetate was without effect. Isobutylmethylxanthine significantly increased inositolmore » uptake, while the increased uptake due to dibutyryl cyclic AMP and forskolin were not statistically significant. Sodium nitroprusside, and activator of guanylate cyclase, and 8-bromo cyclic GMP, were without effect on uptake, as was methylene blue, an inhibitor of guanylate cyclase. Inositol uptake into the aorta was increased when the endothelium was allowed to remain intact, although this effect was likely due to uptake in both the endothelial and smooth muscle cells.« less

BDNF-induced nitric oxide signals in cultured rat hippocampal neurons: time course, mechanism of generation, and effect on neurotrophin secretion.

PubMed

Kolarow, Richard; Kuhlmann, Christoph R W; Munsch, Thomas; Zehendner, Christoph; Brigadski, Tanja; Luhmann, Heiko J; Lessmann, Volkmar

2014-01-01

BDNF and nitric oxide signaling both contribute to plasticity at glutamatergic synapses. However, the role of combined signaling of both pathways at the same synapse is largely unknown. Using NO imaging with diaminofluoresceine in cultured hippocampal neurons we analyzed the time course of neurotrophin-induced NO signals. Application of exogenous BDNF, NT-4, and NT-3 (but not NGF) induced NO signals in the soma and in proximal dendrites of hippocampal neurons that were sensitive to NO synthase activity, TrkB signaling, and intracellular calcium elevation. The effect of NO signaling on neurotrophin secretion was analyzed in BDNF-GFP, and NT-3-GFP transfected hippocampal neurons. Exogenous application of the NO donor sodium-nitroprusside markedly inhibited neurotrophin secretion. However, endogenously generated NO in response to depolarization and neurotrophin stimulation, both did not result in a negative feedback on neurotrophin secretion. These results suggest that a negative feedback of NO signaling on synaptic secretion of neurotrophins operates only at high intracellular levels of nitric oxide that are under physiological conditions not reached by depolarization or BDNF signaling.

BDNF-induced nitric oxide signals in cultured rat hippocampal neurons: time course, mechanism of generation, and effect on neurotrophin secretion

PubMed Central

Kolarow, Richard; Kuhlmann, Christoph R. W.; Munsch, Thomas; Zehendner, Christoph; Brigadski, Tanja; Luhmann, Heiko J.; Lessmann, Volkmar

2014-01-01

BDNF and nitric oxide signaling both contribute to plasticity at glutamatergic synapses. However, the role of combined signaling of both pathways at the same synapse is largely unknown. Using NO imaging with diaminofluoresceine in cultured hippocampal neurons we analyzed the time course of neurotrophin-induced NO signals. Application of exogenous BDNF, NT-4, and NT-3 (but not NGF) induced NO signals in the soma and in proximal dendrites of hippocampal neurons that were sensitive to NO synthase activity, TrkB signaling, and intracellular calcium elevation. The effect of NO signaling on neurotrophin secretion was analyzed in BDNF-GFP, and NT-3-GFP transfected hippocampal neurons. Exogenous application of the NO donor sodium-nitroprusside markedly inhibited neurotrophin secretion. However, endogenously generated NO in response to depolarization and neurotrophin stimulation, both did not result in a negative feedback on neurotrophin secretion. These results suggest that a negative feedback of NO signaling on synaptic secretion of neurotrophins operates only at high intracellular levels of nitric oxide that are under physiological conditions not reached by depolarization or BDNF signaling. PMID:25426021

Microprocessor-controlled hemodynamics: a step towards improved efficiency and safety.

PubMed

Keogh, B E; Jacobs, J; Royston, D; Taylor, K M

1989-02-01

Manual titration of sodium nitroprusside (SNP) is widely used for treatment of hypertension following cardiac surgery. This study compared conventional manual control with control by a research prototype of an automatic infusion module based on a proportional plus integral plus derivative (PID) negative feedback loop. Two groups of coronary artery bypass patients requiring SNP for postoperative hypertension were studied prospectively. In the first group, hypertension was controlled by manual adjustment of the SNP infusion rate, and in the second, the infusion rate was controlled automatically. The actual and desired mean arterial pressures (MAP) over consecutive ten-second epochs were recorded during the period of infusion. The MAP was maintained within 10% of the desired MAP 45.8% of the time in the manual group, compared with 90.0% in the automatic group, and the mean percent error in the automatic group was significantly less than in the manual group (P less than 0.01). It is concluded that adoption of such systems will result in improved patient safety and may facilitate more effective distribution of nursing staff within intensive care units.

A standardized procedure for using human corpus cavernosum strips to evaluate drug activity.

PubMed

Mirone, V; Sorrentino, R; di Villa Bianca, R; Imbimbo, C; Palmieri, A; Fusco, F; Tajana, G; Cirino, G

2000-01-01

The main problem of using human corpus cavernosum (HCC) tissue to perform bioassay is linked to its limited availability further complicated by the heterogeneous source of the tissues used. Here, we show that gender reassignment is a reliable source of human tissue without major ethical problems. Indeed, the entire corpus cavernosum is obtained from the surgery procedure, which allows creating a standardized procedure to prepare HCC strip. In addition, human tissue, if kept in the fridge in the condition described, does not loose its ability to contract to phenylephrine (PE; alpha agonist), angiotensin II (AG II) and KCl up to 4 days. Furthermore, once contracted with PE, HCC relaxes to acetylcholine (endothelium-dependent mechanism); sodium nitroprusside (endothelium-independent mechanism); cromakalim (CRK), a K(ATP) channel opener; or alprostadil, a synthetic PGE2 (ALPR). In conclusion, we have standardized a procedure that allows the use of HCC strips to evaluate drug activity and/or to study pathophysiological mechanisms with an intact functional human tissue up to 4 days from the surgery procedure.

Involvement of cannabinoids in the cardioprotection induced by lipopolysaccharide

PubMed Central

Lagneux, Caroline; Lamontagne, Daniel

2001-01-01

We have examined the involvement of the endocannabinoid system in the cardioprotection triggered by lipopolysaccharide (LPS). Rats were treated with saline or LPS (10 μg Kg−1). 24 h later, hearts were excised, retrogradely perfused, submitted to a low-flow ischaemia (0.6 ml min−1) for 90 min and reperfused for 60 min. Some hearts were perfused with either SR 141716A (a cannabinoid CB1, receptor antagonist 1 μM), SR 144528 (a CB2 receptor anagonist μM), NNLA (3 μM) or sodium nitroprusside (1 μM) 5 min before ischaemia and during the ischaemic period. The cardioprotective effects of LPS treatment, in terms of infarction and functional recovery, were not altered by the perfusion of SR 141716A but abolished by both SR 144528 and NNLA. Finally, SR 144528 abolished the beneficial effects of SNP perfusion. Our results suggest an involvement of endocannabinoids, acting through the CB2 receptors, in the cardioprotection triggered by LPS against myocardial ischaemia. This could be attributed to a relationship between cannabinoids and NO. PMID:11181418

Modelling and multi-parametric control for delivery of anaesthetic agents.

PubMed

Dua, Pinky; Dua, Vivek; Pistikopoulos, Efstratios N

2010-06-01

This article presents model predictive controllers (MPCs) and multi-parametric model-based controllers for delivery of anaesthetic agents. The MPC can take into account constraints on drug delivery rates and state of the patient but requires solving an optimization problem at regular time intervals. The multi-parametric controller has all the advantages of the MPC and does not require repetitive solution of optimization problem for its implementation. This is achieved by obtaining the optimal drug delivery rates as a set of explicit functions of the state of the patient. The derivation of the controllers relies on using detailed models of the system. A compartmental model for the delivery of three drugs for anaesthesia is developed. The key feature of this model is that mean arterial pressure, cardiac output and unconsciousness of the patient can be simultaneously regulated. This is achieved by using three drugs: dopamine (DP), sodium nitroprusside (SNP) and isoflurane. A number of dynamic simulation experiments are carried out for the validation of the model. The model is then used for the design of model predictive and multi-parametric controllers, and the performance of the controllers is analyzed.

Single dose regorafenib-induced hypertensive crisis.

PubMed

Yilmaz, B; Kemal, Y; Teker, F; Kut, E; Demirag, G; Yucel, I

2014-06-01

Gastrointestinal stromal tumors (GISTs) are uncommon tumors of the gastrointestinal (GI) tract. Regorafenib is a new multikinase inhibitor and is approved for the treatment of GISTs in patients who develop resistance to imatinib and sunitinib. The most common drug-related adverse events with regorafenib are hypertension, hand-foot skin reactions, and diarrhea. Grade IV hypertensive side effect has never been reported after a single dose. In this report, we present a case of Grade IV hypertensive side effect (hypertensive crisis and seizure) after a single dose of regorafenib. A 54-year-old male normotensive GIST patient was admitted to the emergency department with seizure and encephalopathy after the first dosage of regorafenib. His blood pressure was 240/140 mmHg upon admission. After intensive treatment with nitrate and nitroprusside, his blood pressure returned to normal levels in five days. Regorafenib was discontinued, and he did not experience hypertension again. This paper reports the first case of Grade IV hypertension after the first dosage of regorafenib. We can suggest that hypertension is an idiosyncratic side effect unrelated to the dosage.

The mechanism of action of lymphokines. IX. The enzymatic basis of hydrogen peroxide production by lymphokine-activated macrophages.

PubMed

Freund, M; Pick, E

1986-08-15

The purpose of this study was to elucidate the biochemical basis of the enhanced hydrogen peroxide (H2O2) production by guinea pig peritoneal macrophages (MP) cultured in lymphokine (LK)-containing medium. The markedly augmented H2O2 generation by these cells, demonstrable by the horseradish peroxidase (HRP)-catalyzed oxidation of phenol red, is distinguished by its lack of dependence on a second stimulus. We demonstrate that H2O2 production is truly spontaneous and is not caused by a stimulant present among the H2O2 assay reagents. The principal candidate for such a role was HRP type II (a mixture of five isoenzymes) that was reported to be capable of eliciting an oxidative burst in MP. Four distinct HRP isoenzymes that were found incapable of provoking an oxidative response were nevertheless adequate for demonstrating H2O2 production by LK-activated MP. Blocking the MP receptor for mannose by the addition of mannan to the assay system resulted in enhanced detection of H2O2 by low concentrations of HRP type II and by three out of four HRP isoenzymes. Treatment of MP with LK-containing medium for 72 hr did not result in a significant change in the activity of cellular superoxide dismutase (SOD) compared with MP cultured for the same length of time in control medium. By using the specific inhibitor of copper, zinc-containing SOD, sodium diethyldithiocarbamate (DDC), and the universal SOD inhibitor, sodium nitroprusside, we found that the predominant enzyme in guinea pig peritoneal MP is probably manganese-containing SOD. Incubation of LK-activated MP with nitroprusside resulted in almost total inhibition of H2O2 production and a simultaneous switch to superoxide (O2-) liberation. Similar exposure to DDC had no effect. These data indicate that H2O2 produced by LK-activated MP is derived exclusively by enzymatic dismutation of O2- mediated by a manganese-containing SOD. The increase in spontaneous H2O2 production induced by LK is therefore secondary to augmented O2- production that occurs at a cellular location where O2- is accessible to SOD. The enzymatic basis of the enhanced oxygen radical production was investigated by determining the kinetic parameters of the O2- -forming NADPH oxidase of resting LK-treated MP in a cellfree system in which O-2 production was induced by sodium dodecyl sulfate. The Km for NADPH and the Vmax of the enzyme of LK-treated MP were not different from those of the enzyme of MP incubated in control medium. We conclude that LK treatment of MP does not modulate the NADPH oxidase itself but, most likely, a process related to activation of the enzyme.

Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip muscle ischemia in humans

NASA Technical Reports Server (NTRS)

Cui, J.; Wilson, T. E.; Shibasaki, M.; Hodges, N. A.; Crandall, C. G.

2001-01-01

To identify whether muscle metaboreceptor stimulation alters baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA, beat-by-beat arterial blood pressure (Finapres), and electrocardiogram were recorded in 11 healthy subjects in the supine position. Subjects performed 2 min of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 2.5 min of posthandgrip muscle ischemia. During muscle ischemia, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.001) during posthandgrip muscle ischemia (-201.9 +/- 20.4 units. beat(-1). mmHg(-1)) when compared with control conditions (-142.7 +/- 17.3 units. beat(-1). mmHg(-1)). No significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. However, both curves shifted during postexercise ischemia to accommodate the elevation in blood pressure and MSNA that occurs with this condition. These data suggest that the sensitivity of baroreflex modulation of MSNA is elevated by muscle metaboreceptor stimulation, whereas the sensitivity of baroreflex of modulate heart rate is unchanged during posthandgrip muscle ischemia.

Indirect determination of thiocyanate with ammonium sulfate and ethanol by extraction-flotation of copper.

PubMed

Li, Q; Wei, W; Liu, Q

2000-10-01

A new method for the indirect determination of thiocyanate with ammonium sulfate and ethanol by extraction-flotation of copper in the presence of ascorbic acid is described. A small amount of Cu(II) is reduced to Cu(I) by ascorbic acid, then Cu(I) is precipitated with SCN-. In the course of phase separation of ethanol from water, the precipitated CuSCN stays in the interface of ethanol and water. A good linear relationship is observed between the flotation yield of Cu(II) and the amount of SCN-. Using 1.0 ml of 1 x 10(-3) M ascorbic acid solution, 50 micrograms of Cu(II), 3.5 g of (NH4)2SO4 and 3.0 ml of ethanol with a total volume of 10 ml, the concentration of thiocyanate could then be determined by determining the flotation yield of Cu(II). The detection limit for thiocyanate is 5 x 10(-5) M. Every parameter was optimized and the reaction mechanism was studied. The method is simple and rapid and it was successfully applied to the determination of thiocyanate in urine and saliva of smokers and non-smokers and in venous blood of patients infused with sodium nitroprusside.

Atrial natriuretic peptide induces acrosomal exocytosis in bovine spermatozoa.

PubMed

Zamir, N; Barkan, D; Keynan, N; Naor, Z; Breitbart, H

1995-08-01

The induction of acrosomal exocytosis in capacitated bull spermatozoa by atrial natriuretic peptide (ANP) was studied in vitro. ANP markedly stimulated acrosomal exocytosis in a calcium-dependent manner. Typically, ANP exerts its action via activation of the ANP receptor (ANPR-A), a particulate guanylyl cyclase-linked receptor, and subsequent formation of guanosine 3',5'-cyclic monophosphate (cGMP). We found that the ANP-induced acrosome reaction was inhibited by the competitive ANPR-A receptor antagonist-anantin, indicating a receptor-mediated effect. We could mimic the effect of ANP on the acrosome reaction by using 8-bromo-cGMP, suggesting that cGMP may serve as a signal transducer mediating the acrosome reaction. Indeed, the ANP-induced acrosome reaction was associated with elevation of cGMP levels. cGMP can also be formed by activation of the soluble form of guanylyl cyclase. Sodium nitroprusside (SNP) stimulated cGMP accumulation and acrosome reaction of capacitated spermatozoa. Thus ANP and the nitric oxide-releasing compound SNP, via activation of guanylyl cyclase (the former activating the particulate and the latter activating the soluble form of the enzyme), may play a significant role in the induction of the acrosome reaction.

Altered central nervous system processing of baroreceptor input following hindlimb unloading in rats

NASA Technical Reports Server (NTRS)

Moffitt, J. A.; Schadt, J. C.; Hasser, E. M.

1999-01-01

The effect of cardiovascular deconditioning on central nervous system processing of baroreceptor afferent activity was evaluated following 14 days of hindlimb unloading (HU). Inactin-anesthetized rats were instrumented with catheters, renal sympathetic nerve electrodes, and aortic depressor nerve electrodes for measurement of mean arterial pressure, heart rate, renal sympathetic nerve activity (RSNA), and aortic depressor nerve activity (ADNA). Baroreceptor and baroreflex functions were assessed during infusion of phenylephrine and sodium nitroprusside. Central processing of baroreceptor afferent input was evaluated by linear regression relating RSNA to ADNA. The maximum baroreflex-elicited increase in RSNA was significantly reduced in HU rats (122 +/- 3.8 vs. 144 +/- 4.9% of baseline RSNA), whereas ADNA was not altered. The slope (-0.18 +/- 0.04 vs. -0.40 +/- 0.04) and y-intercept (121 +/- 3.2 vs. 146 +/- 4.3) of the linear regression relating increases in efferent RSNA to decreases in afferent ADNA during hypotension were significantly reduced in HU rats. There were no differences during increases in arterial pressure. Results demonstrate that the attenuation in baroreflex-mediated increases in RSNA following HU is due to changes in central processing of baroreceptor afferent information rather than aortic baroreceptor function.

Allopurinol prevents nitroglycerin-induced tolerance in rat thoracic aorta.

PubMed

Azarmi, Yadollah; Babaei, Hossein; Alizadeh, Fatemeh; Gharebageri, Afsaneh; Fouladi, Daniel F; Nikkhah, Elhameh

2014-02-01

Xanthine oxidase is an important source of reactive oxygen species; so, it may play a role in the pathogenesis of endothelium dysfunction and its consequences. Allopurinol, a purine analog, is a famous xanthine oxidase inhibitor. This study aimed to investigate possible effects of allopurinol on nitroglycerin tolerance, vasoconstriction, and vasorelaxation in rat aortic ring. Using thoracic aortic rings obtained from male Wistar rats, the effect of allopurinol was examined on nitroglycerin-induced tolerance. In addition, changes of vasoconstriction (by using KCl and phenylephrine) and vasorelaxation (by using carbachol, sodium nitroprusside, and nitroglycerin) were also measured and compared between tissues treated with and without allopurinol. All 3 concentrations of allopurinol (50, 100, and 150 μM) significantly acted against the development of nitroglycerin-induced tolerance in comparison with controls. In terms of vasoconstriction and vasorelaxation, the effect of allopurinol was significant only on carbachol-induced (endothelium related) vasorelaxation in a dose-dependent manner. In conclusion, although allopurinol had no significant effect on the contractile response of the aorta, in accord with the previous data, it significantly intensified endothelium-dependent vasodilation. The inhibitory effect of allopurinol against the development of nitrate-induced tolerance may suggest its clinical benefit and is worth to be studied more extensively.

The effects of angiotensin II on blood perfusion in the rat renal papilla

PubMed Central

Walker, L L; Rajaratne, A A J; Blair-West, J R; Harris, P J

1999-01-01

Systemic infusion of angiotensin II (AII) increased papillary blood perfusion (PBP) measured by laser-Doppler flowmetry in rats, aged about 5 weeks. The mechanisms involved in this response were determined by infusion of AII in the presence of systemic doses of losartan (a type 1 AII receptor antagonist), HOE-140 (a bradykinin B2 receptor antagonist), and an inhibitor of NO production - Nω -nitro-L-arginine (NOLA). Mean arterial blood pressure (MAP) and PBP increased in a dose-dependent manner in response to intravenous infusions of AII. Infusion of losartan abolished these responses to AII but HOE-140 was without effect. Infusion of NOLA abolished the increase in PBP but did not affect the pressor response to AII. Systemic infusion of sodium nitroprusside restored the response to AII in experiments with NOLA infusion. The results indicate that the increase in PBP caused by AII is mediated via angiotensin AT1 receptors and does not involve bradykinin B2 receptors. The AII-induced increase in PBP is dependent upon the presence of NO, thus providing a mechanism for maintenance of papillary perfusion in the face of generalized renal vasoconstriction due to AII. PMID:10432357

A nitric oxide burst precedes apoptosis in angiosperm and gymnosperm callus cells and foliar tissues.

PubMed

Pedroso, M C; Magalhaes, J R; Durzan, D

2000-06-01

Leaves and callus of Kalanchoë daigremontiana and Taxus brevifolia were used to investigate nitric oxide-induced apoptosis in plant cells. The effect of nitric oxide (NO) was studied by using a NO donor, sodium nitroprusside (SNP), a nitric oxide-synthase (NOS) inhibitor, N:(G)-monomethyl-L-arginine (NMMA), and centrifugation (an apoptosis-inducing treatment in these species). NO production was visualized in cells and tissues with a specific probe, diaminofluorescein diacetate (DAF-2 DA). DNA fragmentation was detected in situ by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) method. In both species, NO was detected diffused in the cytosol of epidermal cells and in chloroplasts of guard cells and leaf parenchyma cells. Centrifugation increased NO production, DNA fragmentation and subsequent cell death by apoptosis. SNP mimicked centrifugation results. NMMA significantly decreased NO production and apoptosis in both species. The inhibitory effect of NMMA on NO production suggests that a putative NOS is present in Kalanchoë and Taxus cells. The present results demonstrated the involvement of NO on DNA damage leading to cell death, and point to a potential role of NO as a signal molecule in these plants.

High Concentration of Benzyladenine Solution Stimulates Anthers for Inducing Callus in Ricinus Communis L.

NASA Astrophysics Data System (ADS)

Liu, Ying; Yan, Shuying; Yang, Fuguang; Li, Dongliang; Tang, Jianian; Liu, Guoxuan; Lin, Shiwan; Niu, Sufang; Yang, Yali

2017-12-01

An high-frequency protocol for induction of callus from anther explants of Ricinus communis was described. When anther explants of R. communis was cultured directly onto medium containing 6-benzylaminopurine (BA) induced formation of only poor quality callus that had a low induction frequency of anther callus (10.67%). However, treating the anther explants with high concentrations (7.5-120 mg/L) of BA solution for short time periods (5-80 min) helped to improve the induction frequency and enhance the quality of the callus formation significantly. The best callus induction (41.25%) was observed when anther explants were treated with 15 mg/L BA solution for 10 min before being inoculated onto hormone-free Murashige and Skoog (MS) medium for 30 days. In order to further optimize the culture system, after treated with 15 mg/L BA for 10 min, anther explants were inoculated on the hormone-free MS medium contained concentrations of sodium nitroprusside (SNP). The results showed that SNP significantly promoted the response of callus induction, especially when 8 mg/L SNP was applied, the the highest percentage of callus induction (60.37%) were gained.

Effects of the natural flavonoid delphinidin on diabetic microangiopathy.

PubMed

Bertuglia, S; Malandrino, S; Colantuoni, A

1995-04-01

The purpose of the present study was to investigate the effects of the flavonoid delphinidin chloride (CAS 528-53-0, IdB 1056) on diabetic microangiopathy. Hamsters were injected with alloxan and cheek pouch microcirculation was observed by a fluorescent microscopy technique 90 days from alloxan. The increase in permeability, the number of adhering leukocytes to venular vessel wall and vasodilatory responses to acetylcholine (Ach) and sodium nitroprusside (SNP) were measured. In diabetic group microvascular permeability and the number of sticking leukocytes to the venular endothelium were increased. Vasoconstriction by Ach was observed while the vasodilation by SNP was significantly attenuated in diabetic animals. These results are consistent for a decreased relaxation and suggest also an impairment in the smooth muscle cell function in diabetic arterioles. IdB 1056 exhibited an inhibitory effect on increased microvascular permeability and on leukocytes adhering to the venular vessels. Indeed, the treatment with IdB 1056 in diabetic hamsters pretreated or not with indometacin, a cyclooxygenase inhibitor, restored the relaxant responses to Ach and SNP. In conclusion, the effects of IdB 1056 observed in vivo at the microcirculatory level prevent the injury to endothelial cell function associated with diabetes and/or oxidative stress.

Central N-acetylcysteine effects on baroreflex in juvenile spontaneously hypertensive rats.

PubMed

Valenti, Vitor E; De Abreu, Luiz Carlos; Sato, Monica A; Saldiva, Paulo H N; Fonseca, Fernando L A; Giannocco, Gisele; Riera, Andreas R P; Ferreira, Celso

2011-06-01

In this study, we evaluated the acute effects of central NAC administration on baroreflex in juvenile SHR and Wistar Kyoto (WKY) rats. Male SHR and WKY rats (8-10 weeks old) were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. After basal MAP and HR recordings, the baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 μg/kg, bolus) and a depressor dose of sodium nitroprusside (SNP, 50 μg/kg, bolus). Baroreflex was evaluated before, 5, 15, 30 and 60 minutes after NAC injection into the 4th V. Vehicle treatment did not change baroreflex responses in WKY and SHR. Central NAC slightly but significantly increased basal HR at 15 minutes and significantly reduced PHE-induced increase in MAP 30 and 60 minutes after NAC injection (p < 0.05) in WKY rats. In relation to SHR, NAC decreased HR range 15 and 30 minutes after its administration. In conclusion, acute NAC into the 4th V does not improve baroreflex in juvenile SHR.

Blood vessel adaptation to gravity in a semi-arboreal snake

NASA Technical Reports Server (NTRS)

Conklin, D. J.; Lillywhite, H. B.; Olson, K. R.; Ballard, R. E.; Hargens, A. R.

1996-01-01

The effects of vasoactive agonists on systemic blood vessels were examined with respect to anatomical location and gravity acclimation in the semi-arboreal snake, Elaphe Obsoleta. Major blood vessels were reactive to putative neurotransmitters, hormones or local factors in vessel specific patterns. Catecholamines, adenosine triphosphate, histamine and high potassium (80 mM) stimulated significantly greater tension per unit vessel mass in posterior than anterior arteries. Anterior vessels were significantly more sensitive to catecholamines than midbody and posterior vessels. Angiotensin II stimulated significantly greater tension in carotid artery than in midbody and posterior dorsal aorta. Arginine vasotocin strongly contracted the left and right aortic arches and anterior dorsal aorta. Veins were strongly contracted by catecholamines, high potassium and angiotensin II, but less so by adenosine triphosphate, arginine vasotocin and histamine. Precontracted vessel were relaxed by acetylcholine and sodium nitroprusside, but not by atrial natriuretic peptide or bradykinin. Chronic exposure of snakes to intermittent hypergravity stress ( + 1.5 Gz at tail) did not affect the majority of vessel responses. These data demonstrate that in vitro tension correlates with that catecholamines, as well as other agonists, are important in mediating vascular responses to gravitational stresses in snakes.

The urea decomposition product cyanate promotes endothelial dysfunction

PubMed Central

El-Gamal, Dalia; Rao, Shailaja Prabhakar; Holzer, Michael; Hallström, Seth; Haybaeck, Johannes; Gauster, Martin; Wadsack, Christian; Kozina, Andrijana; Frank, Saša; Schicho, Rudolf; Schuligoi, Rufina; Heinemann, Akos; Marsche, Gunther

2014-01-01

The dramatic cardiovascular mortality of chronic kidney disease patients is attributable in a significant proportion to endothelial dysfunction. Cyanate, a reactive species in equilibrium with urea, is formed in excess in chronic kidney disease. Cyanate is thought to have a causal role in promoting cardiovascular disease, but the underlying mechanisms remain unclear. Immunohistochemical analysis performed in the present study revealed that carbamylated epitopes associate mainly with endothelial cells in human atherosclerotic lesions. Cyanate treatment of human coronary artery endothelial cells reduced expression of endothelial nitric oxide synthase and increased tissue factor and plasminogen activator inhibitor-1 expression. In mice, administration of cyanate - promoting protein carbamylation at levels observed in uremic patients - attenuated arterial vasorelaxation of aortic rings in response to acetylcholine, without affecting sodium nitroprusside-induced relaxation. Total endothelial nitric oxide synthase and nitric oxide production were significantly reduced in aortic tissue of cyanate-treated mice. This coincided with a marked increase of tissue factor and plasminogen activator inhibitor-1 protein levels in aortas of cyanate-treated mice. These data provide evidence that cyanate compromises endothelial functionality in vitro and in vivo and may contribute to the dramatic cardiovascular risk of patients suffering from chronic kidney disease. PMID:24940796

A flatness-based control approach to drug infusion for cardiac function regulation

NASA Astrophysics Data System (ADS)

Rigatos, Gerasimos; Zervos, Nikolaos; Melkikh, Alexey

2016-12-01

A new control method based on differential flatness theory is developed in this article, aiming at solving the problem of regulation of haemodynamic parameters, Actually control of the cardiac output (volume of blood pumped out by heart per unit of time) and of the arterial blood pressure is achieved through the administered infusion of cardiovascular drugs, such as dopamine and sodium nitroprusside. Time delays between the control inputs and the system's outputs are taken into account. Using the principle of dynamic extension, which means that by considering certain control inputs and their derivatives as additional state variables, a state-space description for the heart's function is obtained. It is proven that the dynamic model of the heart is a differentially flat one. This enables its transformation into a linear canonical and decoupled form, for which the design of a stabilizing feedback controller becomes possible. The proposed feedback controller is of proven stability and assures fast and accurate tracking of the reference setpoints by the outputs of the heart's dynamic model. Moreover, by using a Kalman Filter-based disturbances' estimator, it becomes possible to estimate in real-time and compensate for the model uncertainty and external perturbation inputs that affect the heart's model.

Biodegradable membrane-covered stent from chitosan-based polymers.

PubMed

Thierry, Benjamin; Merhi, Yahye; Silver, Jim; Tabrizian, Maryam

2005-12-01

Membrane-covered devices could help treat disease of the vasculature such as aneurysm, rupture, and fistulas. They are also investigated to reduce embolic complication associated with revascularization of saphenous vein graft. The aim of this study is to design a clinically applicable biodegradable membrane-covered stent based on the natural polysaccharide chitosan, which has been developed. The mechanical properties of the membrane is optimized through blending with polyethylene oxide (70:30% Wt CH:PEO). The membrane was able to sustain the mechanical deformation of the supporting self-expandable metallic stents during its deployment. The membrane was demonstrated to resist physiological transmural pressure (burst pressure resistance >500 mm Hg) and presented a high-water permeation resistance (1 mL/cm(2) min(-1) at 120 mmHg). The CH-PEO membrane showed a good hemocompatibility in an ex vivo assay. Heparin and hyaluronan surface complexation with the membrane further reduced platelet adhesion by 50.1 and 63% (p = 0.05). The ability of the membrane-covered devices to be used as a drug reservoir was investigated using the nitric oxide donor sodium nitroprusside (SNP). SNP-loaded membranes displayed significantly reduced platelet adhesion. (c) 2005 Wiley Periodicals, Inc.

Interactions between CO2 chemoreflexes and arterial baroreflexes

NASA Technical Reports Server (NTRS)

Henry, R. A.; Lu, I. L.; Beightol, L. A.; Eckberg, D. L.

1998-01-01

We studied interactions between CO2 chemoreflexes and arterial baroreflexes in 10 supine healthy young men and women. We measured vagal carotid baroreceptor-cardiac reflexes and steady-state fast Fourier transform R-R interval and photoplethysmographic arterial pressure power spectra at three arterial pressure levels (nitroprusside, saline, and phenylephrine infusions) and three end-tidal CO2 levels (3, 4, and 5%, fixed-frequency, large-tidal-volume breathing, CO2 plus O2). Our study supports three principal conclusions. First, although low levels of CO2 chemoreceptor stimulation reduce R-R intervals and R-R interval variability, statistical modeling suggests that this effect is indirect rather than direct and is mediated by reductions of arterial pressure. Second, reductions of R-R intervals during hypocapnia reflect simple shifting of vagally mediated carotid baroreflex responses on the R-R interval axis rather than changes of baroreflex gain, range, or operational point. Third, the influence of CO2 chemoreceptor stimulation on arterial pressure (and, derivatively, on R-R intervals and R-R interval variability) depends critically on baseline arterial pressure levels: chemoreceptor effects are smaller when pressure is low and larger when arterial pressure is high.

Diligustilide releases H2S and stabilizes S-nitrosothiols in ethanol-induced lesions on rat gastric mucosa.

PubMed

Velázquez-Moyado, Josué Arturo; Balderas-López, José Luis; Pineda-Peña, Elizabeth Arlen; Sánchez-Ortiz, Brenda Lorena; Tavares-Carvalho, José Carlos; Navarrete, Andrés

2018-04-01

(Z,Z')-Diligustilide (DLG) or levistolide A is a dimeric phthalide isolated from Ligusticum porteri (Osha), the roots of which are used in the traditional treatment of many diseases including gastric aches. However, its action has not been completely elucidated. We analyzed the contributions of hydrogen sulfide and S-nitrosothiols to the action of DLG. Animals were pretreated with freshly formed in vitro nitrosothiol using Na 2 S and sodium nitroprusside to elucidate participation in the action of DLG. We also evaluated the production of H 2 S in vivo and in real time on the stomach via a specific electrode introduced into the stomachs of anaesthetized animals pretreated with DLG. Treatment with 10 mg/kg DLG increases gastric H 2 S production in vivo from 7.8 ± 0.81 ppm to 13.1 ± 3.01 ppm and prevents the decrease in gastric injury caused by absolute ethanol. In addition, it maintains endogenous concentrations of GSH and NO · . Exogenous S-nitrosothiols protect the gastric mucosa from damage, suggesting that the action of DLG might be associated with S-nitrosothiol and H 2 S formation.

In vivo and in situ monitoring of the nitric oxide stimulus response of single cancer cells by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Su, L.; Chen, Y.; Zhang, G. N.; Wang, L. H.; Shen, A. G.; Zhou, X. D.; Wang, X. H.; Hu, J. M.

2013-04-01

Raman spectroscopy is capable of studying time-resolved information of selected biomolecular distributions inside individual cells without labeling. In this study, Raman spectroscopy was for the first time utilized to in vivo and in situ monitor the cellular response to nitric oxide (NO) in single oral squamous cell carcinoma (OSCC) cells over a period of 24 h. Sodium nitroprusside (SNP) was chosen as a NO donor to be incubated with the OSCC cell line (TCA8113) for certain time intervals. In vivo and in situ Raman analysis revealed that the degradation and conformational changes of nucleic acids, lipids and proteins could be directly observed by changes in the characteristic Raman bands. In comparison with conventional flow cytometric analysis, Raman spectroscopy not only detected more subtle NO-induced chemical changes of cells, where the SNP concentration could be even less than 1 mM, but also provided a full view of the whole chemical components of single cells. Raman spectroscopy therefore is an important candidate for label-free, nondestructive and in situ monitoring of cellular changes in response to chemotherapeutic agents, which could potentially be used in rapid screening of novel drugs.

Baroreflex modulation of muscle sympathetic nerve activity during cold pressor test in humans

NASA Technical Reports Server (NTRS)

Cui, Jian; Wilson, Thad E.; Crandall, Craig G.

2002-01-01

The purpose of this project was to test the hypothesis that baroreceptor modulation of muscle sympathetic nerve activity (MSNA) and heart rate is altered during the cold pressor test. Ten subjects were exposed to a cold pressor test by immersing a hand in ice water for 3 min while arterial blood pressure, heart rate, and MSNA were recorded. During the second and third minute of the cold pressor test, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.005) during the cold pressor test (-244.9 +/- 26.3 units x beat(-1) x mmHg(-1)) when compared with control conditions (-138.8 +/- 18.6 units x beat(-1) x mmHg(-1)), whereas no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that baroreceptors remain capable of modulating MSNA and heart rate during a cold pressor test; however, the sensitivity of baroreflex modulation of MSNA is elevated without altering the sensitivity of baroreflex control of heart rate.

Increase in sensitivity of the baroreceptor reflex following microinjection of carbachol into the posterior hypothalamic nucleus of awake rats.

PubMed

Newey, C R; Martin, J R

2016-01-01

In a rat model, the baroreceptor reflex can be assessed by graded infusions of either phenylephrine or sodium nitroprusside with continuous hemodynamic monitoring. Microinjection of the cholinergic agonist carbachol (CCh) into the posterior hypothalamic nucleus (PHN) evokes an increase in mean arterial pressure and a change in heart rate. Lower doses of CCh evoke only tachycardia, whereas middle and higher doses evoke a biphasic change in heart rate of tachycardia followed by bradycardia. The bradycardia following the microinjection of CCh into the PHN can be attenuated by the previous administration of the vasopressin V1 receptor antagonist [d(CH2 )5 Tyr(Me)] arginine vasopressin (AVPX). Circulating arginine vasopressin (AVP) has been shown to increase the sensitivity of the baroreceptor reflex by stimulating vasopressin V1 receptors in the area postrema. The attenuation by AVPX of the bradycardia that results following the high doses of CCh suggests that AVP is released into the circulation following stimulation of cholinergic systems within the PHN. Thus, microinjection of a high dose of CCh (11 nmol) into the PHN alters the sensitivity of the baroreceptor reflex by increasing peripheral levels of AVP. © 2016 John Wiley & Sons Ltd.

Effects of exercise training and detraining on cutaneous microvascular function in man: the regulatory role of endothelium-dependent dilation in skin vasculature.

PubMed

Wang, Jong-Shyan

2005-01-01

This study investigated how exercise training and detraining affect the cutaneous microvascular function and the regulatory role of endothelium-dependent dilation in skin vasculature. Ten healthy sedentary subjects cycled on an ergometer at 50% of maximal oxygen uptake (VO(2max)) for 30 min daily, 5 days a week, for 8 weeks, and then detrained for 8 weeks. Plasma nitric oxide (NO) metabolites (nitrite plus nitrate) were measured by a microplate fluorometer. The cutaneous microvascular perfusion responses to six graded levels of iontophoretically applied 1% acetylcholine (ACh) and 1% sodium nitroprusside (SNP) in the forearm skin were determined by laser Doppler. After training, (1) resting heart rate and blood pressure were reduced, whereas VO(2max), skin blood flow and cutaneous vascular conductance to acute exercise were enhanced; (2) plasma NO metabolite levels and ACh-induced cutaneous perfusion were increased; (3) skin vascular responses to SNP did not change significantly. However, detraining reversed these effects on cutaneous microvascular function and plasma NO metabolite levels. The results suggest that endothelium-dependent dilation in skin vasculature is enhanced by moderate exercise training and reversed to the pretraining state with detraining.

NO-producing compounds transform neuron responses to glutamate.

PubMed

D'yakonova, T L

2000-01-01

We have previously shown that NO increases the excitatory effects of glutamate and blocks the desensitization of neurons to glutamate in the brain of the common snail. The aim of the present work was to identify the possible effect of NO on inhibitory responses to glutamate in the neurons of this mollusk. Electrophysiological investigations were performed on three identified neurons. The results showed that glutamate (0.05-0.1 mM) initially induced hyperpolarization and blocked the spike activity of these neurons. Simultaneous exposure to glutamate and the NO donor nitroprusside or preincubation with an NO donor had the effect that cells again responded to glutamate with depolarization and excitation. The transformed excitatory response lasted several minutes and could be reproduced even after 24 h of washing. The NO synthase blocker monomethylarginine blocked the excitatory response to glutamate. Another agonist of glutamate receptors, N-methyl-D-aspartate (NMDA, 0.1-1 mM), initially had excitatory effects on these neurons; this effect was significantly enhanced after transformation of the response to glutamate by NO donors. The results obtained here show that NO is involved in transforming the inhibitory responses to glutamate to excitatory responses, and that this effect may be mediated by NMDA-type receptors.

Oxidative damage induced by heat stress could be relieved by nitric oxide in Trichoderma harzianum LTR-2.

PubMed

Yu, Yang; Yang, Zijun; Guo, Kai; Li, Zhe; Zhou, Hongzi; Wei, Yanli; Li, Jishun; Zhang, Xinjian; Harvey, Paul; Yang, Hetong

2015-04-01

Trichoderma harzianum is an important commercial biocontrol fungal agent. The temperature has been shown to be an important parameter and strain-specific to the mycelia growth of fungi, but less report makes the known of the mechanisms in T. harzianum. In our study, a 6-h treatment of heat increased the thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO) concentration in mycelia to 212 and 230 % the level of the control, respectively. The exogenous NO donor sodium nitroprusside (150 μM) reduced the TBARS concentration to 53 % of that under heat stress (HS). At the same time, the NO-specific scavenger at 250 μM, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-1-oxyl-3-oxide, prevented the exogenous NO-relieved TBARS accumulation under HS. The increased NO concentration under HS was reduced 41 % by the NO synthase (NOS) inhibitor L-N(G)-nitroarginine methyl ester, but not the nitrate reductase (NR) inhibitor tungstate. Our study exhibited that NO can protect the mycelia of T. harzianum from HS and reduce the oxidative damage by enhancing the activity of NOS and NR.

Effects of nitric oxide on red blood cell deformability.

PubMed

Bor-Kucukatay, Melek; Wenby, Rosalinda B; Meiselman, Herbert J; Baskurt, Oguz K

2003-05-01

In addition to its known action on vascular smooth muscle, nitric oxide (NO) has been suggested to have cardiovascular effects via regulation of red blood cell (RBC) deformability. The present study was designed to further explore this possibility. Human RBCs in autologous plasma were incubated for 1 h with NO synthase (NOS) inhibitors [N(omega)-nitro-l-arginine methyl ester (l-NAME) and S-methylisothiourea], NO donors [sodium nitroprusside (SNP) and diethylenetriamine (DETA)-NONOate], an NO precursor (l-arginine), soluble guanylate cyclase inhibitors (1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one and methylene blue), and a potassium channel blocker [triethylammonium (TEA)]. After incubation, RBC deformability at various shear stresses was determined by ektacytometry. Both NOS inhibitors significantly reduced RBC deformability above a threshold concentration, whereas the NO donors increased deformability at optimal concentrations. NO donors, as well as the NO precursor l-arginine and the potassium blocker TEA, were able to reverse the effects of NOS inhibitors. Guanylate cyclase inhibition reduced RBC deformation, with both SNP and DETA-NONOate able to reverse this effect. These results thus indicate the importance of NO as a determinant of RBC mechanical behavior and suggest its regulatory role for normal RBC deformability.

Acute blood pressure effects of YC-1-induced activation of soluble guanylyl cyclase in normotensive and hypertensive rats

PubMed Central

Rothermund, Lars; Friebe, Andreas; Paul, Martin; Koesling, Doris; Kreutz, Reinhold

2000-01-01

We used YC-1 as a pharmacological tool to investigate the short-term blood pressure effects of NO-independent activation of sGC in normotensive and hypertensive rats. Four groups of normotensive Wistar-Kyoto rats were treated by i.v. injection with vehicle (V), YC-1 (YC-1), sodium nitroprusside (SNP), or YC-1 and SNP (YC-1+SNP). Hypertension was induced in four additional groups of WKY rats by 3 weeks of oral treatment with L-NAME. These animals were investigated with the same protocol as the normotensive animals: L-NAME/V, L-NAME/YC-1, L-NAME/SNP, L-NAME/YC-1+SNP. YC-1 lowered mean arterial blood pressure (MAP) in normotensive and hypertensive animals similarly to SNP alone (P<0.05, respectively). The combination of YC-1 with SNP caused a strong decrease of MAP in both the hypertensive and normotensive animals (P<0.05, respectively). SNP with YC-1 also induced a pronounced cyclic GMP increase in the aorta. This study shows for the first time the blood pressure lowering potential of bimodal targeting of the NO-sGC-system. PMID:10807655

Hypertensive Crisis, Burden, Management, and Outcome at a Tertiary Care Center in Karachi.

PubMed

Almas, Aysha; Ghouse, Ayaz; Iftikhar, Ahmed Raza; Khursheed, Munawwar

2014-01-01

Objectives. Hypertension, if uncontrolled, can lead to hypertensive crisis. We aim to determine the prevalence of hypertensive crisis, its management, and outcome in patients presenting to a tertiary care center in Karachi. Methods. This was a cross-sectional study conducted at the Aga Khan University, Karachi, Pakistan. Adult inpatients (>18 yrs) presenting to the ER who were known hypertensive and had uncontrolled hypertension were included. Results. Out of 1336 patients, 28.6% (387) had uncontrolled hypertension. The prevalence of hypertensive crisis among uncontrolled hypertensive was 56.3% (218). Per oral calcium channel blocker; 35.4% (137) and intravenous nitrate; 22.7% (88) were the most commonly administered medication in the ER. The mean (SD) drop in SBP in patients with hypertensive crisis on intravenous treatment was 53.1 (29) mm Hg and on per oral treatment was 43 (27) mm Hg. The maximum mean (SD) drop in blood pressure was seen by intravenous sodium nitroprusside; 80 (51) mm Hg in SBP. Acute renal failure was the most common complication with a prevalence of 11.5% (24). Conclusion. The prevalence of hypertensive crisis is high. Per oral calcium channel blocker and intravenous nitrate are the most commonly administered medications in our setup.

[Hypertensive crisis in children and adolescents].

PubMed

Skrzypczyk, Piotr; Roszkowska-Blaim, Maria; Daniel, Maria

2013-12-01

Hypertensive crisis is a sudden rise in blood pressure above 99 c. for sex, age and height +5 mm Hg. Depending on patient's symptoms, hypertensive crisis can be divided into hypertensive emergency severe arterial hypertension with target organ insufficiency and/r damage (central nervous system, heart, kidney, eye), and hypertensive urgency - severe arterial hypertension without target organ insufficiency and damage with non-specific symptoms like: headaches, vertigo, nasal bleeding, nausea, and vomiting. The most common causes of hypertensive crisis in neonates and infants are renal artery thrombosis, broncho-pulmonary dysplasia, and coarctation of aorta; in older children - kidney diseases and renal artery stenosis. In neonates and infants symptoms of cardiac failure predominate, whereas in older children symptoms from central nervous system (headaches, nausea, vomiting, changes in level of consciousness, seizures, focal deficits). Hypertensive crisis is treated with fast- and short-acting medications; 25% reduction of blood pressure within first 8 hours is recommended, with complete normalization within 24-48 hours. Hypertensive emergency should be treated with intravenous agents (labetalol, hydralazine, nicardipine, and sodium nitroprusside), hypertensive urgency with intravenous or oral agents like nifedipine, isradipine, clonidine and minoxidil. Nicardipine is a first-choice medication in neonates.

Lack of effect of sodium nitroprusside on insulin-mediated blood flow and glucose disposal in the elderly.

PubMed

Meneilly, G S; Battistini, B; Floras, J S

2000-03-01

Insulin increases skeletal muscle blood flow in healthy young subjects by a nitric oxide (NO)-dependent mechanism. Impairment of this mechanism may contribute to the insulin resistance of normal aging, a state characterized by reduced endothelial production of NO, an attenuated effect of insulin on skeletal muscle blood flow, and resistance to insulin-mediated glucose uptake (IMGU). We tested the hypothesis that the NO donor sodium nitroprusside (SNP) would augment insulin-mediated vasodilation and thus increase IMGU in healthy elderly subjects. Experiments were performed with young (n = 9; age, 25 +/- 1 years; body mass index [BMI], 24 +/- 1 kg/m2) and old (n = 10; age, 78 +/- 2 years; BMI, 25 +/- 1 kg/m2) healthy subjects. Each group underwent two studies in random order. In one study (control), insulin was infused using the euglycemic clamp protocol for 240 minutes at a rate of 40 mU/m2/min (young) and 34 mU/m2/min (old). In the other study (SNP), SNP was coinfused with insulin from 120 to 240 minutes. At regular intervals in each study, blood samples were obtained and calf blood flow was measured using venous occlusion plethysmography. Glucose and insulin values were similar in control and SNP studies in both age groups. In the young, SNP had no effect on blood flow to the calf, but its action in calf resistance vessels augmented insulin-mediated vasodilation, since incremental calf vascular conductance was greater during SNP infusion (control v SNP, 0.027 +/- 0.002 v 0.040 +/- 0.008 mL/100 mL/min/mm Hg, P< .0001). However, SNP had no effect on insulin-mediated glucose disposal. In the elderly, SNP reduced the blood flow to the calf, but this was countered by its effect on calf resistance vessels such that vascular conductance was unaffected (control v SNP, 0.012 +/- 0.003 v 0.011 +/- 0.003 mL/100 mL/min/mm Hg, P = nonsignificant [NS]). Steady-state (180 to 240 minutes) glucose disposal (control v SNP, 7.47 +/- 0.47 v 6.54 +/- 0.56 mg/kg/min, P < .01) rates were significantly lower during SNP infusion. In summary, systemic infusion of SNP did not increase insulin-mediated glucose disposal in either young or old subjects. Thus, the present findings do not support the concept that increasing NO availability will enhance glucose disposal in either age group. However, because the incremental increases in IMGU during SNP infusion paralleled the changes in blood supply to the calf rather than calf vascular conductance, any potential benefits on NO delivery in elderly subjects may have been offset by the direct or reflex effects of systemic hypotension. Other stimuli to NO production that do not cause hypotension must be tested before this therapeutic strategy can be considered as a potential means for enhancing the metabolic actions of insulin in the elderly.

Study of the Adsorption Space of Modified Clinoptilolites

DOE PAGES

Roque-Malherbe, Rolando; Costa-Hernandez,, Alba N.; Rivera-Maldonado, Christymarie; ...

2013-05-25

Carbon dioxide (CO 2) adsorption is an important adsorbent characterization method and a significant industrial process. In separation and recovery technology, the adsorption of the CO 2 is important to reduce the concentration of this gas considered as one of the greenhouse gases. Natural zeolites, particularly clinoptilolite, are widely applied as adsorbents. In the present research, the structure, composition and morphology of modified with hexafluorosilicate (HFSi) and orthophosphoric acid (H 3PO 4) clinoptilolites were investigated by characterizations and measurements made with, X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy-energy dispersive X-ray analysis (SEM-EDAX) and gravimetric adsorption. In addition, themore » surface Chemistry of the modified clinoptilolites was analyzed by applying diffuse reflectance fourier transform infrared spectrometry (DRIFTS). Further, the interaction of CO 2 within the adsorption space of these modified clinoptilolites and a synthetic ZSM-5 zeolite was studied with the help of adsorption measurements. An appropriate theoretical methodology for the analysis of the XRD and adsorption data was applied. The calculated cell parameters of the tested are similar to those reported for a typical clinoptilolite of: a = 17.662 Å, b = 17.911 Å, c = 7.407 Å and β = 116.40 The resolution of the TGA derivative profiles indicated the presence of two steps for water release, one of them represents the loss of majority of the water present in the micropores. This was evidenced as a broad peak centered at about 50°C for the CSW-HFSi-0.1, but at 100 °C for the samples CSW-HFSi-0.4. The SEM micrographs corresponding to the modified clinoptilolites, was evidenced that the CSW zeolite shows secondary particles exhibiting diameters from 3 to 40 μm, formed by primary clinoptilolite crystallites showing a crystallite size, Φ = 40 nm. The EDAX elemental analysis it can be demonstrated that the exchange process replaced about 85% of the charge compensating ions. The DRIFT spectra of the modified clinoptilolites, specifically, CSW-HFSi-0.1, show a narrow band at about: 3,740 cm-l corresponding to terminal silanol groups (Si-OH) and a band 3,600-3,650 cm -1 resulting from extra-framework Al-OH. With the precision of the measured micropore volumes related to the excellent fitting of the adsorption data by the D-R isotherm equation, it can be affirm that carbon adsorption took only place in the micropore region. The isosteric heat of adsorption calculated for the modified clinoptilolites was greater than those values reported of ZSM-5 zeolite, particle packing silica, dealuminated Y zeolite (DAY) Cd, Zn and Ni-nitroprussides and Cu-nitroprusside and a Ni-MOF. With the obtained result it can be concluded that the modified clinoptilolites with HFSi showed a quality as adsorbent comparable to commercial synthetic zeolites.« less

Oxidative and antioxidative responses in the wheat-Azospirillum brasilense interaction.

PubMed

Méndez-Gómez, Manuel; Castro-Mercado, Elda; Alexandre, Gladys; García-Pineda, Ernesto

2016-03-01

Azospirillum is a plant growth-promoting rhizobacteria (PGPR) able to enhance the growth of wheat. The aim of this study was to test the effect of Azospirillum brasilense cell wall components on superoxide (O2·(-)) production in wheat roots and the effect of oxidative stress on A. brasilense viability. We found that inoculation with A. brasilense reduced O2·(-) levels by approx. 30 % in wheat roots. Inoculation of wheat with papain-treated A. brasilense, a Cys protease, notably increased O2·(-) production in all root tissues, as was observed by the nitro blue tetrazolium (NBT) reduction. However, a 24-h treatment with rhizobacteria lipopolysaccharides (50 and 100 μg/mL) alone did not affect the pattern of O2·(-) production. Analysis of the effect of plant cell wall components on A. brasilense oxidative enzyme activity showed no changes in catalase activity but a decrease in superoxide dismutase activity in response to polygalacturonic acid treatment. Furthermore, A. brasilense growth was only affected by high concentrations of H2O2 or paraquat, but not by sodium nitroprusside. Our results suggest that rhizobacterial cell wall components play an important role in controlling plant cell responses and developing tolerance of A. brasilense to oxidative stress produced by the plant.

Nitric oxide donors or nitrite counteract copper-[dithiocarbamate](2)-mediated tumor cell death and inducible nitric oxide synthase down-regulation: possible role of a nitrosyl-copper [dithiocarbamate](2) complex.

PubMed

Rhenals, Maricela Viola; Strasberg-Rieber, Mary; Rieber, Manuel

2010-02-25

In contrast to other metal-dithiocarbamate [DEDTC] complexes, the copper-DEDTC complex is highly cytotoxic, inducing oxidative stress, preferentially in tumor cells. Because nitric oxide (NO) forms adducts with Cu[DEDTC](2), we investigated whether NO donors like S-nitroso-N-acetyl penicillamine (SNAP) or sodium nitroprusside (SNP), and nitrite, a NO decomposition product, modulate Cu[DEDTC](2) cytotoxicity against human tumor cells. We show that apoptosis-associated PARP cleavage and inducible nitric oxide synthase (iNOS) down-regulation induced by nanomolar Cu[DEDTC](2), are counteracted by 50 muM SNAP, SNP, or CoCl(2), an inducer of hypoxia and NO signaling. Nitrite was stochiometrically effective in antagonizing Cu[DEDTC](2) cytotoxicity and inducing shifts in the absorption spectrum of the binary complex in the 280 and 450 nm regions. Subtoxic concentrations of Cu[DEDTC](2) became lethal when tumor cells were pretreated with c-PTIO, a membrane-impermeable scavenger for extracellular NO. Our results suggest that: (a) reactive oxygen species induced by Cu[DEDTC](2) are scavenged by nitrite released from NO, (b) the extent of lethality of Cu[DEDTC](2) is dependent on the reciprocal formation of an inactive ternary Cu[DEDTC](2)NO copper-nitrosyl complex.

Nitric oxide enhances Oct-4 expression in bone marrow stem cells and promotes endothelial differentiation.

PubMed

Chu, Ling; Jiang, Yuehua; Hao, Hong; Xia, Yong; Xu, Jian; Liu, Zehao; Verfaillie, Catherine M; Zweier, Jay L; Liu, Zhenguo

2008-09-04

This study was designed to investigate the role of nitric oxide (NO) in bone marrow stem cells and their differentiation into endothelial cells in vitro. Adult mouse bone marrow multipotent progenitor cells (MAPCs) were used as the source of stem cells. Oct-4 expression (both mRNA and protein) was significantly increased by up to 68.0% in MAPCs when incubated with NO donors DETA-NONOate or sodium nitroprusside (SNP) in a concentration-dependant manner (n=3, P<0.05). However, the cell proliferation was dramatically decreased by over 3-folds when treated with DETA-NONOate or SNP for 48 h (n=3, P<0.05). When MAPCs were exposed to DETA-NONOate (100 microM) for the first 48 h during differentiation, the expression (both mRNA and protein) of vWF was significantly increased at day 14 in the differentiating cells. The effects of DETA-NONOate or SNP on cell proliferation, Oct-4 expression and endothelial differentiation of MAPCs were not affected by the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one or cGMP analog 8-Br-cGMP. These data indicate that NO may regulate both the pluripotency and differentiation of MAPCs via a cGMP-independent mechanism.

Nitric Oxide Regulates Lung Carcinoma Cell Anoikis through Inhibition of Ubiquitin-Proteasomal Degradation of Caveolin-1*

PubMed Central

Chanvorachote, Pithi; Nimmannit, Ubonthip; Lu, Yongju; Talbott, Siera; Jiang, Bing-Hua; Rojanasakul, Yon

2009-01-01

Anoikis, a detachment-induced apoptosis, is a principal mechanism of inhibition of tumor cell metastasis. Tumor cells can acquire anoikis resistance which is frequently observed in metastatic lung cancer. This phenomenon becomes an important obstacle of efficient cancer therapy. Recently, signaling mediators such as caveolin-1 (Cav-1) and nitric oxide (NO) have garnered attention in metastasis research; however, their role and the underlying mechanisms of metastasis regulation are largely unknown. Using human lung carcinoma H460 cells, we show that NO impairs the apoptotic function of the cells after detachment. The NO donors sodium nitroprusside and diethylenetriamine NONOate inhibit detachment-induced apoptosis, whereas the NO inhibitors aminoguanidine and 2-(4-carboxyphenyl) tetramethylimidazoline-1-oxyl-3-oxide promote this effect. Resistance to anoikis in H460 cells is mediated by Cav-1, which is significantly down-regulated after cell detachment through a non-transcriptional mechanism involving ubiquitin-proteasomal degradation. NO inhibits this down-regulation by interfering with Cav-1 ubiquitination through a process that involves protein S-nitrosylation, which prevents its proteasomal degradation and induction of anoikis by cell detachment. These findings indicate a novel pathway for NO regulation of Cav-1, which could be a key mechanism of anoikis resistance in tumor cells. PMID:19706615

Nitric oxide regulates lung carcinoma cell anoikis through inhibition of ubiquitin-proteasomal degradation of caveolin-1.

PubMed

Chanvorachote, Pithi; Nimmannit, Ubonthip; Lu, Yongju; Talbott, Siera; Jiang, Bing-Hua; Rojanasakul, Yon

2009-10-09

Anoikis, a detachment-induced apoptosis, is a principal mechanism of inhibition of tumor cell metastasis. Tumor cells can acquire anoikis resistance which is frequently observed in metastatic lung cancer. This phenomenon becomes an important obstacle of efficient cancer therapy. Recently, signaling mediators such as caveolin-1 (Cav-1) and nitric oxide (NO) have garnered attention in metastasis research; however, their role and the underlying mechanisms of metastasis regulation are largely unknown. Using human lung carcinoma H460 cells, we show that NO impairs the apoptotic function of the cells after detachment. The NO donors sodium nitroprusside and diethylenetriamine NONOate inhibit detachment-induced apoptosis, whereas the NO inhibitors aminoguanidine and 2-(4-carboxyphenyl) tetramethylimidazoline-1-oxyl-3-oxide promote this effect. Resistance to anoikis in H460 cells is mediated by Cav-1, which is significantly down-regulated after cell detachment through a non-transcriptional mechanism involving ubiquitin-proteasomal degradation. NO inhibits this down-regulation by interfering with Cav-1 ubiquitination through a process that involves protein S-nitrosylation, which prevents its proteasomal degradation and induction of anoikis by cell detachment. These findings indicate a novel pathway for NO regulation of Cav-1, which could be a key mechanism of anoikis resistance in tumor cells.

Histamine paw edema of mice was increased and became H[sub 2]-antagonist sensitive by co-injection of nitric oxide forming agents, but serotonin paw edema was decreased

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oyanagui, Yoshihiko; Sato, Sachio

1993-01-01

Nitric oxide (NO) surprisingly caused the opposite effect on histamine and serotonin edema. The local injection of acidified nitrite (0.3-30 [mu]g/paw which correspond 10 [mu]g-1mg/kg) increased histamine edema of mice up to 45[plus minus]4% and suppressed serotonin edema to 90[plus minus]3%. Other NO-generators (nitroprusside sodium and hydroxylamine) showed similar effects. These results were in accordance with previous data on endogenous NO. Methylene blue (MB, 30ng/paw which corresponds to 1 [mu]g/kg) suppressed histamine edema (62[plus minus]3%) and increased serotonin edema (43[plus minus]3%) in normal mice, being reversed by acidified nitrite. This suggests the involvement of guanosine 3[prime], 5[prime]-cyclic monophosphate (cGMP) formationmore » for the action of NO. Histamine edema became sensitive to H[sub 2]-antagonist, cimetidine, by co-injection of 30 [mu]g/paw (which corresponds to 1mg/kg) acidified nitrite (ED[sub 50] = 30 [mu]g/kg versus [much gt] 1mg/kg). NO seemed to modify the histamine receptor(s) or tautomeric form of histamine. NO, O[sup [minus

Thiopental inhibits nitric oxide production in rat aorta.

PubMed

Castillo, C; Asbun, J; Escalante, B; Villalón, C M; López, P; Castillo, E F

1999-12-01

We studied whether thiopental affects endothelial nitric oxide dependent vasodilator responses and nitrite production (an indicator of nitric oxide production) elicited by acetylcholine, histamine, and A23187 in rat aorta (artery in which nitric oxide is the main endothelial relaxant factor). In addition, we evaluated the barbiturate effect on nitric oxide synthase (NOS) activity in both rat aorta and kidney homogenates. Thiopental (10-100 microg/mL) reversibly inhibited the endothelium-dependent relaxation elicited by acetylcholine, histamine, and A23187. On the contrary, this anesthetic did not modify the endothelium-independent but cGMP-dependent relaxation elicited by sodium nitroprusside (1 nM - 1 microM) and nitroglycerin (1 nM - 1 microM), thus excluding an effect of thiopental on guanylate cyclase of vascular smooth muscle. Thiopental (100 microg/mL) inhibited both basal (87.8+/-14.3%) and acetylcholine- or A23187-stimulated (78.6+/-3.9 and 39.7+/-5.6%, respectively) production of nitrites in aortic rings. In addition the barbiturate inhibited (100 microg/mL) the NOS (45+/-4 and 42.8+/-9%) in aortic and kidney homogenates, respectively (measured as 14C-labeled citrulline production). In conclusion, thiopental inhibition of endothelium-dependent relaxation and nitrite production in aortic rings strongly suggests an inhibitory effect on NOS. Thiopental inhibition of the NOS provides further support to this contention.

Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ignarro, L.J.; Buga, G.M.; Wood, K.S.

1987-12-01

The objective of this study was to determine whether nitric oxide (NO) is responsible for the vascular smooth muscle relaxation elicited by endothelium-derived relaxing factor (EDRF). EDRF is an unstable humoral substance released from artery and vein that mediates the action of endothelium-dependent vasodilators. NO is and unstable endothelium-independent vasodilator that is released from vasodilator drugs such as nitroprusside and glyceryl trinitrate. The authors have repeatedly observed that the actions of NO on vascular smooth muscle closely resemble those of EDRF. In the present study the vascular effects of EDRF released from perfused bovine intrapulmonary artery and vein were comparedmore » with the effects of NO delivered by superfusion over endothelium-denuded arterial and venous strips arranged in a cascade. EDRF was indistinguishable from NO in that both were labile inactivated by pyrogallol or superoxide anion, stabilized by superoxide dismutase, and inhibited by oxyhemoglobin or potassium. Both EDRF and NO produced comparable increases in cyclic GMP accumulation in artery and vein, and this cyclic GMP accumulation was inhibited by pyrogallol, oxyhemoglobin, potassium, and methylene blue. EDRF was identified chemically as NO, or a labile nitroso species, by two procedures. Thus, EDRF released from artery and vein possesses identical and biological and chemical properties as NO.« less

Modulatory Effect of 2-(4-Hydroxyphenyl)amino-1,4-naphthoquinone on Endothelial Vasodilation in Rat Aorta.

PubMed

Palacios, Javier; Cifuentes, Fredi; Valderrama, Jaime A; Benites, Julio; Ríos, David; González, Constanza; Chiong, Mario; Cartes-Saavedra, Benjamín; Lafourcade, Carlos; Wyneken, Ursula; González, Pamela; Owen, Gareth I; Pardo, Fabián; Sobrevia, Luis; Buc Calderon, Pedro

The vascular endothelium plays an essential role in the control of the blood flow. Pharmacological agents like quinone (menadione) at various doses modulate this process in a variety of ways. In this study, Q7 , a 2-phenylamino-1,4-naphthoquinone derivative, significantly increased oxidative stress and induced vascular dysfunction at concentrations that were not cytotoxic to endothelial or vascular smooth muscle cells. Q7 reduced nitric oxide (NO) levels and endothelial vasodilation to acetylcholine in rat aorta. It also blunted the calcium release from intracellular stores by increasing the phenylephrine-induced vasoconstriction when CaCl 2 was added to a calcium-free medium but did not affect the influx of calcium from extracellular space. Q7 increased the vasoconstriction to BaCl 2 (10 -3  M), an inward rectifying K + channels blocker, and blocked the vasodilation to KCl (10 -2  M) in aortic rings precontracted with BaCl 2 . This was recovered with sodium nitroprusside (10 -8  M), a NO donor. In conclusion, Q7 induced vasoconstriction was through a modulation of cellular mechanisms involving calcium fluxes through K + channels, and oxidative stress induced endothelium damage. These findings contribute to the characterization of new quinone derivatives with low cytotoxicity able to pharmacologically modulate vasodilation.

In-vivo Fourier domain optical coherence tomography as a new tool for investigation of vasodynamics in the mouse model.

PubMed

Meissner, Sven; Müller, Gregor; Walther, Julia; Morawietz, Henning; Koch, Edmund

2009-01-01

In-vivo imaging of the vascular system can provide novel insight into the dynamics of vasoconstriction and vasodilation. Fourier domain optical coherence tomography (FD-OCT) is an optical, noncontact imaging technique based on interferometry of short-coherent near-infrared light with axial resolution of less than 10 microm. In this study, we apply FD-OCT as an in-vivo imaging technique to investigate blood vessels in their anatomical context using temporally resolved image stacks. Our chosen model system is the murine saphenous artery and vein, due to their small inner vessel diameters, sensitive response to vasoactive stimuli, and advantageous anatomical position. The vascular function of male wild-type mice (C57BL/6) is determined at the ages of 6 and 20 weeks. Vasoconstriction is analyzed in response to dermal application of potassium (K(+)), and vasodilation in response to sodium nitroprusside (SNP). Vasodynamics are quantified from time series (75 sec, 4 frames per sec, 330 x 512 pixels per frame) of cross sectional images that are analyzed by semiautomated image processing software. The morphology of the saphenous artery and vein is determined by 3-D image stacks of 512 x 512 x 512 pixels. Using the FD-OCT technique, we are able to demonstrate age-dependent differences in vascular function and vasodynamics.

N,N-diacetyl-L-cystine improves endothelial function in atherosclerotic Watanabe heritable hyperlipidaemic rabbits.

PubMed

Pettersson, Knut S; Eliasson, Ulla Brandt; Abrahamsson, Tommy; Wågberg, Maria; Carrier, Martin; Kengatharan, Ken M

2007-01-01

N,N-diacetyl-L-cystine (DiNAC), a novel immunomodulator, stimulates contact sensitivity/delayed type hypersensitivity reactions in mice induced by oxazolone and reduces atherosclerosis in Watanabe heritable hyperlipidaemic (WHHL) rabbits. Forty-week-old WHHL rabbits were given DiNAC (3 micromol/kg per day) for 8 weeks, and endothelium-mediated dilatation was investigated in vivo using pulse wave analysis. A significant improvement in endothelial function was found after 3 weeks of treatment, which was further improved after 8 weeks. For experiments on isolated blood vessels, 40-week-old rabbits were treated for 3 weeks. Treatment did not affect plasma lipid levels. At termination, aortic rings from the thoracic and abdominal aorta were contracted with phenylephrine in vitro. Concentration-effect curves to acetylcholine and the calcium ionophore A 23187 were used to measure endothelium-mediated vasodilatation, and nitroprusside to elicit endothelium-independent relaxations. Abdominal aorta relaxations were generally larger than in thoracic aorta. DiNAC improved endothelium-dependent relaxations in the abdominal but not in the thoracic aorta. This effect was independent of the degree of atherosclerosis. It is concluded that DiNAC improved endothelial function in atherosclerotic rabbit arteries in vivo and in vitro, and may represent a new treatment modality for atherosclerosis-related diseases.

Asthma causes inflammation of human pulmonary arteries and decreases vasodilatation induced by prostaglandin I2 analogs.

PubMed

Foudi, Nabil; Badi, Aouatef; Amrane, Mounira; Hodroj, Wassim

2017-12-01

Asthma is a chronic inflammatory disease associated with increased cardiovascular events. This study assesses the presence of inflammation and the vascular reactivity of pulmonary arteries in patients with acute asthma. Rings of human pulmonary arteries obtained from non-asthmatic and asthmatic patients were set up in organ bath for vascular tone monitoring. Reactivity was induced by vasoconstrictor and vasodilator agents. Protein expression of inflammatory markers was detected by western blot. Prostanoid releases and cyclic adenosine monophosphate (cAMP) levels were quantified using specific enzymatic kits. Protein expression of cluster of differentiation 68, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and cyclooxygenase-2 was significantly increased in arteries obtained from asthmatic patients. These effects were accompanied by an alteration of vasodilatation induced by iloprost and treprostinil, a decrease in cAMP levels and an increase in prostaglandin (PG) E 2 and PGI 2 synthesis. The use of forskolin (50 µmol/L) has restored the vasodilatation and cAMP release. No difference was observed between the two groups in reactivity induced by norepinephrine, angiotensin II, PGE 2 , KCl, sodium nitroprusside, and acetylcholine. Acute asthma causes inflammation of pulmonary arteries and decreases vasodilation induced by PGI 2 analogs through the impairment of cAMP pathway.

Comparative Transcriptome Analysis of the Necrotrophic Fungus Ascochyta rabiei during Oxidative Stress: Insight for Fungal Survival in the Host Plant

PubMed Central

Singh, Kunal; Nizam, Shadab; Sinha, Manisha; Verma, Praveen K.

2012-01-01

Localized cell death, known as the hypersensitive response (HR), is an important defense mechanism for neutralizing phytopathogens. The hallmark of the HR is an oxidative burst produced by the host plant. We aimed to identify genes of the necrotrophic chickpea blight fungus Ascochyta rabiei that are involved in counteracting oxidative stress. A subtractive cDNA library was constructed after menadione treatment, which resulted in the isolation of 128 unigenes. A reverse northern blot was used to compare transcript profiles after H2O2, menadione and sodium nitroprusside treatments. A total of 70 unigenes were found to be upregulated by more than two-fold following menadione treatment at different time intervals. A large number of genes not previously associated with oxidative stress were identified, along with many stress-responsive genes. Differential expression patterns of several genes were validated by quantitative real-time PCR (qRT-PCR) and northern blotting. In planta qRT-PCR of several selected genes also showed differential expression patterns during infection and disease progression. These data shed light on the molecular responses of the phytopathogen A. rabiei to overcome oxidative and nitrosative stresses and advance the understanding of necrotrophic fungal pathogen survival mechanisms. PMID:22427966

L-arginine as dietary supplement for improving microvascular function.

PubMed

Melik, Ziva; Zaletel, Polona; Virtic, Tina; Cankar, Ksenija

2017-01-01

Reduced availability of nitric oxide leads to dysfunction of endothelium which plays an important role in the development of cardiovascular diseases. The aim of the present study was to determine whether the dietary supplement L-arginine improves the endothelial function of microvessels by increasing nitric oxide production. We undertook experiments on 51 healthy male volunteers, divided into 4 groups based on their age and physical activity since regular physical activity itself increases endothelium-dependent vasodilation. The skin laser Doppler flux was measured in the microvessels before and after the ingestion of L-arginine (0.9 g). The endothelium-dependent vasodilation was assessed by acetylcholine iontophoresis and the endothelium-independent vasodilation by sodium nitroprusside iontophoresis. In addition, we measured endothelium-dependent and endothelium-independent vasodilation in 81 healthy subjects divided into four age groups. After the ingestion of L-arginine, the endothelium-dependent vasodilation in the young trained subjects increased (paired t-test, p < 0.05), while in the other groups it remained the same. There were no differences in the endothelium-independent vasodilation after ingestion of L-arginine. With aging endothelium-independent vasodilation decreased while endothelium-dependent vasodilation remained mainly unchanged. Obtained results demonstrated that a single dose of L-arginine influences endothelium-dependent vasodilation predominantly in young, trained individuals.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nally, J.V.; Clarke, H.S.; Grecos, G.P.

To assess the effect of CAP on individual kidney function in ..mu..RAS, the authors compared computer assisted 90 second and 15 minute /sup 99m/Tc-DTPA renal flow studies vs /sup 131/I-Hippuran renography with and without CAP. In Group 1 (n=10), angiograms, split function C/sub PAH/, DTPA and Hippuran studies were performed in dogs pre and post ..mu..RAS. Group II animals (n=8) with milder stenosis underwent the same protocol, plus DTPA and Hippuran studies, C/sub PAH/, and C/sub IN/ were performed during CAP (Captopril 1.5 mg/kg bolus and 1.5 mg/min x 60 min.) Recovery DTPA and Hippuran studies (Rec) were performed andmore » were also obtained using nitroprusside (NP) to lower MP to a similar degree as CAP. The authors conclude /sup 99m/Tc-DTPA studies proved superior to Hipurran renography in both Groups I and II. With mild ..mu..RAS, CAP induced a decrease in ipsilateral GFR resulting in striking changes in the /sup 99m/Tc-DTPA curves such that all were now diagnostic of uRAS. These changes appeared specific for CAP and independent of MAP reduction with NP, and /sup 99m/Tc-DTPA renal flow studies with CAP unmask unilateral angiotension II dependent renal hemodynamic changes.« less

The Dynamics of the Defense Strategy of Pea Induced by Exogenous Nitric Oxide in Response to Aphid Infestation.

PubMed

Woźniak, Agnieszka; Formela, Magda; Bilman, Piotr; Grześkiewicz, Katarzyna; Bednarski, Waldemar; Marczak, Łukasz; Narożna, Dorota; Dancewicz, Katarzyna; Mai, Van Chung; Borowiak-Sobkowiak, Beata; Floryszak-Wieczorek, Jolanta; Gabryś, Beata; Morkunas, Iwona

2017-02-05

The aim of this study was to investigate the effect of exogenous nitric oxide (NO), i.e., S -nitrosoglutathione (GSNO) and sodium nitroprusside (SNP), on the metabolic status of Pisum sativum L. cv. Cysterski leaves infested by Acyrthosiphon pisum Harris, population demographic parameters and A. pisum feeding activity. A reduction in the level of semiquinone radicals in pea seedling leaves pretreated with exogenous NO occurred 24 h after A. pisum infestation, which was earlier than in non-pretreated leaves. A decrease in the level of O₂ •- was observed in leaves pretreated with GSNO and infested by aphids at 48 and 72 h post-infestation (hpi). Directly after the pretreatment with GSNO, an increase in the level of metal ions was recorded. NO considerably induced the relative mRNA levels for phenylalanine ammonia-lyase in 24-h leaves pretreated with NO donors, both non-infested and infested. NO stimulated the accumulation of pisatin in leaves until 24 h. The Electrical Penetration Graph revealed a reduction in the feeding activity of the pea aphid on leaves pretreated with NO. The present study showed that foliar application of NO donors induced sequentially defense reactions of pea against A. pisum and had a deterrent effect on aphid feeding and limited the population growth rate.

Nitric oxide induced by polyamines involves antioxidant systems against chilling stress in tomato (Lycopersicon esculentum Mill.) seedling.

PubMed

Diao, Qian-Nan; Song, Yong-Jun; Shi, Dong-Mei; Qi, Hong-Yan

Polyamines (PAs) and nitric oxide (NO) are vital signals in modulating plant response to abiotic stress. However, to our knowledge, studies on the relationship between NO and PAs in response to cold stress in tomato are limited. Accordingly, in this study, we investigated the effects of putrescine (Put) and spermidine (Spd) on NO generation and the function of Spd-induced NO in the tolerance of tomato seedling under chilling stress. Spd increased NO release via the nitric oxide synthase (NOS)-like and nitrate reductase (NR) enzymatic pathways in the seedlings, whereas Put had no such effect. Moreover, H 2 O 2 might act as an upstream signal to stimulate NO production. Both exogenous NO donor (sodium nitroprusside (SNP)) and Spd enhanced chilling tolerance in tomato, thereby protecting the photosynthetic system from damage. Compared to chilling treatment alone, Spd enhanced the gene expressions of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), and their enzyme activities in tomato leaves. However, a scavenger or inhibitor of NO abolished Spd-induced chilling tolerance and blocked the increased expression and activity due to Spd of these antioxidant enzymes in tomato leaves under chilling stress. The results showed that NO induced by Spd plays a crucial role in tomato's response to chilling stress.

LeMAPK1, LeMAPK2, and LeMAPK3 are associated with nitric oxide-induced defense response against Botrytis cinerea in the Lycopersicon esculentum fruit.

PubMed

Zheng, Yanyan; Hong, Hui; Chen, Lin; Li, Jingyuan; Sheng, Jiping; Shen, Lin

2014-02-12

Nitric oxide (NO) and mitogen-activated protein kinases (MAPKs) are signal molecules involved in the disease resistance of plants. To investigate the role of tomato MAPKs in the NO-mediated defense response, mature green tomatoes (Lycopersicon esculentum Mill. cv. Qian-xi) were treated with a MAPKs inhibitor (1,4-diamino-2,3-dicyano-1,4-bis(o-amino-phenylmercapto) butadiene (U0126)), NO donor sodium nitroprusside (SNP), and SNP plus U0126. Treatment with U0126 increased the incidence of disease and size of lesion areas in the tomato fruits after being inoculated with Botrytis cinerea. NO enhanced the resistance of the tomato fruits against Botrytis cinerea invasion and the activities of nitric oxide synthase, Chitinase, β-1,3-glucanase, polyphenol oxidase, and phenylalanine ammonia-lyase. However, the effects of NO on disease resistance were weakened by the MAPKs inhibitor. Meanwhile, the relative expression of LeMAPK1, LeMAPK2, and LeMAPK3 in the (SNP + U0126)-treated fruits was lower than that in the SNP-treated fruits. The results suggest that LeMAPK1/2/3 are involved in NO-induced disease resistance of tomato fruits against Botrytis cinerea.

Immunocytology on microwave-fixed cells reveals rapid and agonist-specific changes in subcellular accumulation patterns for cAMP or cGMP.

PubMed Central

Barsony, J; Marx, S J

1990-01-01

We developed a method for cAMP and cGMP immunocytology based upon fixation by microwave irradiation. Fixation by microwave irradiation prevented three problems found with other fixation methods: nucleotide loss from cells, nucleotide diffusion within cells, and chemical modification of immunologic epitopes. Six agonists (four that stimulate adenylate cyclase and two that stimulate guanylate cyclase) produced cAMP or cGMP accumulation patterns that were agonist-specific, dose-dependent, detectable at physiologic concentrations of hormone, and time-dependent within 15 sec to 30 min. cAMP accumulation after 1 mM forskolin was greatest in the nucleus. Isoproterenol, prostaglandin E2, or calcitonin caused initial accumulation of cAMP along the plasma membrane, but later accumulation was greater in the cytoplasm. With calcitonin the later accumulation of cAMP was selectively perinuclear and along the nuclear membrane. Sodium nitroprusside stimulated cGMP accumulation diffusely throughout the cytoplasm. Atrial natriuretic peptide initiated cGMP accumulation near the plasma membrane, and cGMP accumulation moved from there into the cytoplasm. In conclusion, microwave irradiation preserved cell structure and allowed visualization of expected as well as unsuspected changes in intracellular accumulation patterns of cAMP and cGMP. Images PMID:2153973

Nitric oxide induced by polyamines involves antioxidant systems against chilling stress in tomato (Lycopersicon esculentum Mill.) seedling*#

PubMed Central

Diao, Qian-Nan; Song, Yong-Jun; Shi, Dong-Mei; Qi, Hong-Yan

2016-01-01

Polyamines (PAs) and nitric oxide (NO) are vital signals in modulating plant response to abiotic stress. However, to our knowledge, studies on the relationship between NO and PAs in response to cold stress in tomato are limited. Accordingly, in this study, we investigated the effects of putrescine (Put) and spermidine (Spd) on NO generation and the function of Spd-induced NO in the tolerance of tomato seedling under chilling stress. Spd increased NO release via the nitric oxide synthase (NOS)-like and nitrate reductase (NR) enzymatic pathways in the seedlings, whereas Put had no such effect. Moreover, H2O2 might act as an upstream signal to stimulate NO production. Both exogenous NO donor (sodium nitroprusside (SNP)) and Spd enhanced chilling tolerance in tomato, thereby protecting the photosynthetic system from damage. Compared to chilling treatment alone, Spd enhanced the gene expressions of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), and their enzyme activities in tomato leaves. However, a scavenger or inhibitor of NO abolished Spd-induced chilling tolerance and blocked the increased expression and activity due to Spd of these antioxidant enzymes in tomato leaves under chilling stress. The results showed that NO induced by Spd plays a crucial role in tomato’s response to chilling stress. PMID:27921397

Abnormal Neurocirculatory Control During Exercise in Humans with Chronic Renal Failure

PubMed Central

Park, Jeanie; Middlekauff, Holly R.

2014-01-01

Abnormal neurocirculatory control during exercise is one important mechanism leading to exercise intolerance in patients with both end-stage renal disease (ESRD) and earlier stages of chronic kidney disease (CKD). This review will provide an overview of mechanisms underlying abnormal neurocirculatory and hemodynamic responses to exercise in patients with kidney disease. Recent studies have shown that ESRD and CKD patients have an exaggerated increase in blood pressure (BP) during both isometric and rhythmic exercise. Subsequent studies examining the role of the exercise pressor reflex in the augmented pressor response revealed that muscle sympathetic nerve activity (MSNA) was not augmented during exercise in these patients, and metaboreflex-mediated increases in MSNA were blunted, while mechanoreflex-mediated increases were preserved under basal conditions. However, normalizing the augmented BP response during exercise via infusion of nitroprusside (NTP), and thereby equalizing baroreflex-mediated suppression of MSNA, an important modulator of the final hemodynamic response to exercise, revealed that CKD patients had an exaggerated increase in MSNA during isometric and rhythmic exercise. In addition, mechanoreflex-mediated control was augmented, and metaboreceptor blunting was no longer apparent in CKD patients with baroreflex normalization. Factors leading to mechanoreceptor sensitization, and other mechanisms underlying the exaggerated exercise pressor response, such as impaired functional sympatholysis, should be investigated in future studies. PMID:25458430

Transcriptome analysis of nitric oxide-responsive genes in upland cotton (Gossypium hirsutum).

PubMed

Huang, Juan; Wei, Hengling; Li, Libei; Yu, Shuxun

2018-01-01

Nitric oxide (NO) is an important signaling molecule with diverse physiological functions in plants. It is therefore important to characterize the downstream genes and signal transduction networks modulated by NO. Here, we identified 1,932 differentially expressed genes (DEGs) responding to NO in upland cotton using high throughput tag sequencing. The results of quantitative real-time polymerase chain reaction (qRT-PCR) analysis of 25 DEGs showed good consistency. Gene Ontology (GO) and KEGG pathway were analyzed to gain a better understanding of these DEGs. We identified 157 DEGs belonging to 36 transcription factor (TF) families and 72 DEGs related to eight plant hormones, among which several TF families and hormones were involved in stress responses. Hydrogen peroxide and malondialdehyde (MDA) contents were increased, as well related genes after treatment with sodium nitroprusside (SNP) (an NO donor), suggesting a role for NO in the plant stress response. Finally, we compared of the current and previous data indicating a massive number of NO-responsive genes at the large-scale transcriptome level. This study evaluated the landscape of NO-responsive genes in cotton and identified the involvement of NO in the stress response. Some of the identified DEGs represent good candidates for further functional analysis in cotton.

Resection of subvalvular aortic stenosis. Surgical and perioperative management in seven dogs.

PubMed

Komtebedde, J; Ilkiw, J E; Follette, D M; Breznock, E M; Tobias, A H

1993-01-01

Open heart surgery was performed during cardiopulmonary bypass (CPB) to surgically correct subvalvular aortic stenosis in seven dogs. After initiation of total CPB, cardiac arrest was induced by antegrade and retrograde administration of blood cardioplegia. The subvalvular fibrous stenosis was resected through a transverse aortotomy. Intraoperatively and postoperatively, dobutamine, nitroprusside, lidocaine, blood(-products), and crystalloid solutions were used to manage hypotension and optimize cardiac index. Aortic cross-clamp time varied from 73 to 166 minutes, and duration of CPB varied from 130 to 210 minutes. Iatrogenic incision into the mitral valve in two dogs was the most significant intraoperative complication. Postoperative complications included: hypoproteinemia (n = 7), premature ventricular depolarization (n = 6), increased systemic vascular resistance index (n = 5), increased O2 extraction (n = 3), pulmonary edema (n = 2), and decreased cardiac index (n = 1). All seven dogs were discharged alive and in stable condition. Six dogs are alive and in stable condition after a mean follow up of 15.8 months. This is the first detailed report of CPB in a series of clinical veterinary patients. Using the techniques described in this paper, open heart surgery of considerable duration can be performed successfully in dogs with significant myocardial hypertrophy and endomyocardial fibrosis secondary to subvalvular aortic stenosis.

The NO signaling pathway differentially regulates KCC3a and KCC3b mRNA expression.

PubMed

Di Fulvio, Mauricio; Lauf, Peter K; Adragna, Norma C

2003-11-01

Nitric oxide (NO) donors and protein kinase G (PKG) acutely up-regulate K-Cl cotransporter-1 and -3 (KCC1 and KCC3) mRNA expression in vascular smooth muscle cells (VSMCs). Here, we report the presence, relative abundance, and regulation by sodium nitroprusside (SNP) of the novel KCC3a and KCC3b mRNAs, in primary cultures of rat VSMCs. KCC3a and KCC3b mRNAs were expressed in an approximate 3:1 ratio, as determined by semiquantitative RT-PCR analysis. SNP as well as YC-1 and 8-Br-cGMP, a NO-independent stimulator of soluble guanylyl cyclase (sGC) and PKG, respectively, increased KCC3a and KCC3b mRNA expression by 2.5-fold and 8.1-fold in a time-dependent manner, following a differential kinetics. Stimulation of the NO/sGC/PKG signaling pathway with either SNP, YC-1, or 8-Br-cGMP decreased the KCC3a/KCC3b ratio from 3.0+/-0.4 to 0.9+/-0.1. This is the first report on a differential regulation by the NO/sGC/PKG signaling pathway of a cotransporter and of KCC3a and KCC3b mRNA expression.

Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats

NASA Technical Reports Server (NTRS)

Brooks-Asplund, Esther M.; Shoukas, Artin A.; Kim, Soon-Yul; Burke, Sean A.; Berkowitz, Dan E.

2002-01-01

We hypothesized that estradiol treatment would improve vascular dysfunction commonly associated with obesity, hyperlipidemia, and insulin resistance. A sham operation or 17beta-estradiol pellet implantation was performed in male lean and obese Zucker rats. Maximal vasoconstriction (VC) to phenylephrine (PE) and potassium chloride was exaggerated in control obese rats compared with lean rats, but estradiol significantly attenuated VC in the obese rats. Estradiol reduced the PE EC50 in all groups. This effect was cyclooxygenase independent, because preincubation with indomethacin reduced VC response to PE similarly in a subset of control and estrogen-treated lean rats. Endothelium-independent vasodilation (VD) to sodium nitroprusside was similar among groups, but endothelium-dependent VD to ACh was significantly impaired in obese compared with lean rats. Estradiol improved VD in lean and obese rats by decreasing EC50 but impaired function by decreasing maximal VD. The shift in EC50 corresponded to an upregulation in nitric oxide synthase III protein expression in the aorta of the estrogen-treated obese rats. In summary, estrogen treatment improves vascular function in male insulin-resistant, obese rats, partially via an upregulation of nitric oxide synthase III protein expression. These effects are counteracted by adverse factors, such as hyperlipidemia and, potentially, a release of an endothelium-derived contractile agent.

A redox-based mechanism for induction of interleukin-1 production by nitric oxide in a human colonic epithelial cell line (HT29-Cl.16E).

PubMed Central

Vallette, G; Jarry, A; Branka, J E; Laboisse, C L

1996-01-01

We evaluated the effects of two NO donors, sodium nitroprusside (SNP) and 3-morpholino-sydnonimine (SIN-1), characterized by alternative redox states, i.e. nitrosonium ion (NO+) and nitric oxide (NO.) respectively, on intracellular interleukin-1 (IL-1) production, by a human colonic epithelial cell line (HT29-Cl.16E). SNP was able to induce intracellular IL-1 alpha production up to 10 h incubation, in a dose-dependent manner. Several experiments provide evidence that the NO+ redox form, and not the free radical NO., is implicated in the IL-1 alpha production: (i) SIN-1, devoid of any NO+ character, led to a very weak IL-1 production as compared with SNP; (ii) the reductive action of a thiol such as cysteine on NO+ led to a dose-dependent increase in NO, concentration, measured as NO2-/NO3- accumulation, and to large decrease in IL-1 production. Dibutyryl cGMP had no effect on IL-1 production, this finding supporting the concept that a cGMP-independent pathway is involved in the intracellular signalling of NO+. Together these results point out that NO, depending on its redox form, is able to modulate IL-1 production in cultured colonic epithelial cells. PMID:8546706

A redox-based mechanism for induction of interleukin-1 production by nitric oxide in a human colonic epithelial cell line (HT29-Cl.16E).

PubMed

Vallette, G; Jarry, A; Branka, J E; Laboisse, C L

1996-01-01

We evaluated the effects of two NO donors, sodium nitroprusside (SNP) and 3-morpholino-sydnonimine (SIN-1), characterized by alternative redox states, i.e. nitrosonium ion (NO+) and nitric oxide (NO.) respectively, on intracellular interleukin-1 (IL-1) production, by a human colonic epithelial cell line (HT29-Cl.16E). SNP was able to induce intracellular IL-1 alpha production up to 10 h incubation, in a dose-dependent manner. Several experiments provide evidence that the NO+ redox form, and not the free radical NO., is implicated in the IL-1 alpha production: (i) SIN-1, devoid of any NO+ character, led to a very weak IL-1 production as compared with SNP; (ii) the reductive action of a thiol such as cysteine on NO+ led to a dose-dependent increase in NO, concentration, measured as NO2-/NO3- accumulation, and to large decrease in IL-1 production. Dibutyryl cGMP had no effect on IL-1 production, this finding supporting the concept that a cGMP-independent pathway is involved in the intracellular signalling of NO+. Together these results point out that NO, depending on its redox form, is able to modulate IL-1 production in cultured colonic epithelial cells.

[Role of NO signal in ABA-induced phenolic acids accumulation in Salvia miltiorrhiza hairy roots].

PubMed

Shen, Lihong; Ren, Jiahui; Jin, Wenfang; Wang, Ruijie; Ni, Chunhong; Tong, Mengjiao; Liang, Zongsuo; Yang, Dongfeng

2016-02-01

To investigate roles of nitric oxide (NO) signal in accumulations of phenolic acids in abscisic.acid (ABA)-induced Salvia miltiorrhiza hairy roots, S. miltiorrhiza hairy roots were treated with different concentrations of sodium nitroprusside (SNP)-an exogenous NO donor, for 6 days, and contents of phenolic acids in the hairy roots are determined. Then with treatment of ABA and NO scavenger (2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylimidazoline-1- oxyl-3-oxide, c-PTIO) or NO synthase inhibitor (NG-nitro-L-arginine methyl ester, L-NAME), contents of phenolic acids and expression levels of three key genes involved in phenolic acids biosynthesis were detected. Phenolic acids production in S. miltiorrhiza hairy roots was most significantly improved by 100 µmoL/L SNP. Contents of RA and salvianolic acid B increased by 3 and 4 folds. ABA significantly improved transcript levels of PAL (phenylalanine ammonia lyase), TAT (tyrosine aminotransferase) and RAS (rosmarinic acid synthase), and increased phenolic acids accumulations. However, with treatments of ABA+c-PTIO or ABA+L-NAME, accumulations of phenolic acids and expression levels of the three key genes were significantly inhibited. Both NO and ABA can increase accumulations of phenolic acids in S. miltiorrhiza hairy roots. NO signal probably mediates the ABA-induced phenolic acids production.

Comparison of a New Cobinamide-Based Method to a Standard Laboratory Method for Measuring Cyanide in Human Blood

PubMed Central

Swezey, Robert; Shinn, Walter; Green, Carol; Drover, David R.; Hammer, Gregory B.; Schulman, Scott R.; Zajicek, Anne; Jett, David A.; Boss, Gerry R.

2013-01-01

Most hospital laboratories do not measure blood cyanide concentrations, and samples must be sent to reference laboratories. A simple method is needed for measuring cyanide in hospitals. The authors previously developed a method to quantify cyanide based on the high binding affinity of the vitamin B12 analog, cobinamide, for cyanide and a major spectral change observed for cyanide-bound cobinamide. This method is now validated in human blood, and the findings include a mean inter-assay accuracy of 99.1%, precision of 8.75% and a lower limit of quantification of 3.27 µM cyanide. The method was applied to blood samples from children treated with sodium nitroprusside and it yielded measurable results in 88 of 172 samples (51%), whereas the reference laboratory yielded results in only 19 samples (11%). In all 19 samples, the cobinamide-based method also yielded measurable results. The two methods showed reasonable agreement when analyzed by linear regression, but not when analyzed by a standard error of the estimate or paired t-test. Differences in results between the two methods may be because samples were assayed at different times on different sample types. The cobinamide-based method is applicable to human blood, and can be used in hospital laboratories and emergency rooms. PMID:23653045

Mechanisms of the palmitoylcarnitine-induced response in vascular endothelial cells.

PubMed

Taki, H; Muraki, K; Imaizumi, Y; Watanabe, M

1999-09-01

The mechanisms of Ca2+ mobilization induced by palmitoylcarnitine (Palcar) in rabbit aortic endothelial cells (ETCs) were examined using electrophysiological techniques. The results obtained were compared with those induced by acetylcholine (ACh). When a rabbit aortic muscle preparation with an intact endothelium was treated with 10 microM Palcar, the ACh-induced relaxation was markedly attenuated, whereas endothelium-independent relaxation caused by sodium nitroprusside was not affected. Under perforated-patch whole-cell-clamp conditions, the application of Palcar over the concentration range 0.3 and 10 microM elicited a slowly activating outward current (IPalcar-out), whereas ACh induced a rapidly activating outward current (IACh). A potassium channel blocker, 4-aminopyridine, significantly inhibited both IPalcar-out and IACh. Removal of external Ca2+ almost abolished IPalcar-out. Under the same conditions, however, IACh remained transient. Addition of cation channel blockers SK&F96365 and La3+ inhibited IPalcar-out more effectively than IACh. Application of staurosporine, an inhibitor of protein kinase C, affected neither IACh nor IPalcar-out. In contrast, treatment of ETCs with pertussis toxin (PTX) reduced IACh and almost abolished IPalcar-out. These findings demonstrate that, in ETCs, Palcar induces Ca2+ influx via the activation of PTX-sensitive GTP-binding protein, leading to the activation of Ca(2+)-dependent K+ current and hyperpolarization of the cell.

Hypertensive Crisis, Burden, Management, and Outcome at a Tertiary Care Center in Karachi

PubMed Central

Almas, Aysha; Ghouse, Ayaz; Iftikhar, Ahmed Raza; Khursheed, Munawwar

2014-01-01

Objectives. Hypertension, if uncontrolled, can lead to hypertensive crisis. We aim to determine the prevalence of hypertensive crisis, its management, and outcome in patients presenting to a tertiary care center in Karachi. Methods. This was a cross-sectional study conducted at the Aga Khan University, Karachi, Pakistan. Adult inpatients (>18 yrs) presenting to the ER who were known hypertensive and had uncontrolled hypertension were included. Results. Out of 1336 patients, 28.6% (387) had uncontrolled hypertension. The prevalence of hypertensive crisis among uncontrolled hypertensive was 56.3% (218). Per oral calcium channel blocker; 35.4% (137) and intravenous nitrate; 22.7% (88) were the most commonly administered medication in the ER. The mean (SD) drop in SBP in patients with hypertensive crisis on intravenous treatment was 53.1 (29) mm Hg and on per oral treatment was 43 (27) mm Hg. The maximum mean (SD) drop in blood pressure was seen by intravenous sodium nitroprusside; 80 (51) mm Hg in SBP. Acute renal failure was the most common complication with a prevalence of 11.5% (24). Conclusion. The prevalence of hypertensive crisis is high. Per oral calcium channel blocker and intravenous nitrate are the most commonly administered medications in our setup. PMID:26464857

Baroreflex modulation of sympathetic nerve activity to muscle in heat-stressed humans

NASA Technical Reports Server (NTRS)

Cui, Jian; Wilson, Thad E.; Crandall, Craig G.

2002-01-01

To identify whether whole body heating alters arterial baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA and beat-by-beat arterial blood pressure were recorded in seven healthy subjects during acute hypotensive and hypertensive stimuli in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature (P < 0.01), MSNA (P < 0.01), heart rate (P < 0.01), and skin blood flow (P < 0.001), whereas mean arterial blood pressure did not change significantly (P > 0.05). During both normothermic and heat stress conditions, MSNA increased and then decreased significantly when blood pressure was lowered and then raised via intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure during heat stress (-128.3 +/- 13.9 U x beats(-1) x mmHg(-1)) was similar (P = 0.31) with normothermia (-140.6 +/- 21.1 U x beats(-1) x mmHg(-1)). Moreover, no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that arterial baroreflex modulation of MSNA and heart rate are not altered by whole body heating, with the exception of an upward shift of these baroreflex curves to accommodate changes in these variables that occur with whole body heating.

The effects of anti-obesity intervention with orlistat and sibutramine on microvascular endothelial function.

PubMed

Al-Tahami, Belqes Abdullah Mohammad; Ismail, Ab Aziz Al-Safi; Bee, Yvonne Tee Get; Awang, Siti Azima; Salha Wan Abdul Rani, Wan Rimei; Sanip, Zulkefli; Rasool, Aida Hanum Ghulam

2015-01-01

Obesity is associated with impaired microvascular endothelial function. We aimed to determine the effects of orlistat and sibutramine treatment on microvascular endothelial function, anthropometric and lipid profile, blood pressure (BP), and heart rate (HR). 76 subjects were recruited and randomized to receive orlistat 120 mg three times daily or sibutramine 10 mg daily for 9 months. Baseline weight, BMI, BP, HR and lipid profile were taken. Microvascular endothelial function was assessed using laser Doppler fluximetry and iontophoresis process. Maximum change (max), percent change (% change) and peak flux (peak) in perfusion to acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis were used to quantify endothelium dependent and independent vasodilatations. 24 subjects in both groups completed the trial. After treatment, weight and BMI were decreased for both groups. AChmax, ACh % change and ACh peak were increased in orlistat-treated group but no difference was observed for sibutramine-treated group. BP and total cholesterol (TC) were reduced for orlistat-treated group. HR was reduced for orlistat-treated group but was increased in sibutramine-treated group. 9 months treatment with orlistat significantly improved microvascular endothelial function. This was associated with reductions in weight, BMI, BP, HR, TC and low density lipoprotein cholesterol. No effect was seen in microvascular endothelial function with sibutramine.

Inhibitory effect of hot-water extract from dried fruit of Crataegus pinnatifida on low-density lipoprotein (LDL) oxidation in cell and cell-free systems.

PubMed

Chu, Chia-Yih; Lee, Miao-Jane; Liao, Chuen-Lan; Lin, Wea-Lung; Yin, Yu-Fang; Tseng, Tsui-Hwa

2003-12-17

The dried fruit of Crataegus pinnatifida, a local soft drink material and medical herb, was found to possess potential against oxidative stress. In the preliminary study, the antioxidant potential of a hot-water extract obtained from the dried fruit of C. pinnatifida (CF-H) was evaluated in terms of its capacity of quenching 1,1-diphenyl-2-picrylhydrazyl free radicals (EC(50) = 0.118 mg/mL). After content analysis, it was found that CF-H is mainly composed of polyphenols including flavonoids (6.9%), procyanidins (2.2%), (+)-catechin (0.5%), and (-)-epicatechin (0.2%). The antioxidative bioactivity of CF-H had been assess previously using the models of CuSO(4) as cell-free system and sodium nitroprusside (SNP) plus macrophage RAW 264.7 cells as cell system to induce human low-density lipoprotein oxidation. CF-H was found to inhibit relative electrophoretic mobility and thiobarbituric acid reactive substances at the concentration of 0.5-1.0 mg/mL in the cell-free system and at 0.01-0.10 mg/mL in the cell system. Furthermore, it was found that CF-H decreased the SNP-induced cell lipid peroxidation and reduced glutathione depletion.

Effect of nabumetone treatment on vascular responses of the thoracic aorta in rat experimental arthritis.

PubMed

Ulker, S; Onal, A; Hatip, F B; Sürücü, A; Alkanat, M; Koşay, S; Evinç, A

2000-04-01

Nabumetone is a nonsteroidal anti-inflammatory (NSAI) drug which is known to cause less gastrointestinal damage than other NSAI drugs. This study was performed to evaluate whether nabumetone treatment might alter the vascular aberrations related to inflammation in a rat model of adjuvant-induced arthritis. Nabumetone treatment (120 or 240 mg x kg(-1) x day(-1), orally) was initiated on the 15th day of adjuvant inoculation and continued for 14 days. Arthritic lesions, vascular contractile and relaxant responses and gastroduodenal histopathological preparations were evaluated 29 days after adjuvant inoculation. The contractile responses of aortic rings to phenylephrine and KCl were increased in grade 2 arthritic rats. In grade 3 arthritis only the phenylephrine contractility was decreased. The relaxant responses to acetylcholine and sodium nitroprusside were decreased in grades 2 and 3. In healthy rats, nabumetone did not change the vascular responses. After treatment of arthritic rats with nabumetone, both the contractile and relaxant response of the aortic rings returned to normal, and arthritic score and paw swelling were reduced. Gastroduodenal histopathology did not show erosions or ulcers in any of the groups. In conclusion, nabumetone improved the systemic signs and vascular alterations in experimental arthritis without showing any gastrointestinal side effects. Copyright 2000 S. Karger AG, Basel.

Tributyltin contributes in reducing the vascular reactivity to phenylephrine in isolated aortic rings from female rats.

PubMed

Rodrigues, Samya Mere L; Ximenes, Carolina F; de Batista, Priscila R; Simões, Fabiana V; Coser, Pedro Henrique P; Sena, Gabriela C; Podratz, Priscila L; de Souza, Leticia N G; Vassallo, Dalton V; Graceli, Jones B; Stefanon, Ivanita

2014-03-21

Organotin compounds such as tributyltin (TBT) are used as antifouling paints by shipping companies. TBT inhibits the aromatase responsible for the transformation of testosterone into estrogen. Our hypothesis is that TBT modulates the vascular reactivity of female rats. Female Wistar rats were treated daily (Control; CONT) or TBT (100 ng/kg) for 15 days. Rings from thoracic aortas were incubated with phenylephrine (PHE, 10(-10)-10(-4) M) in the presence and absence of endothelium, and in the presence of N(G)-Nitro-L-Arginine Methyl Ester (L-NAME), tetraethylammonium (TEA) and apocynin. TBT decreased plasma levels of estrogen and the vascular response to PHE. In the TBT group, the vascular reactivity was increased in the absence of endothelium, L-NAME and TEA. The decrease in PHE reactivity during incubation with apocynin was more evident in the TBT group. The sensitivity to acetylcholine (ACh) and sodium nitroprusside (SNP) was reduced in the TBT group. TBT increased collagen, reduced α1-smooth muscle actin. Female rats treated with TBT for 15 days showed morphology alteration of the aorta and decreased their vascular reactivity, probably due to mechanisms dependent on nitric oxide (NO) bioavailability, K(+) channels and an increase in oxidative stress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effects of chlorogenic acid on carbachol-induced contraction of mouse urinary bladder.

PubMed

Kaneda, Takeharu; Sasaki, Noriyasu; Urakawa, Norimoto; Shimizu, Kazumasa

2018-01-01

Chlorogenic acid (CGA) is a polyphenol found in coffee and medicinal herbs such as Lonicera japonica. In this study, the effect of CGA-induced relaxation on carbachol (CCh)-induced contraction of mouse urinary bladder was investigated. CGA (30-300 μg/ml) inhibited CCh- or U46619-induced contraction in a concentration-dependent manner. SQ22536 (adenylyl cyclase inhibitor) recovered CGA-induced relaxation of CCh-induced contraction; however, ODQ (guanylyl cyclase inhibitor) did not have the same effect. In addition, 3-isobutyl-1-methylxanthine (IBMX) enhanced CGA-induced relaxation; however, forskolin or sodium nitroprusside did not have the same effect. Moreover, Ro 20-1724, a selective phosphodiesterase (PDE) 4 inhibitor, enhanced CGA-induced relaxation, but vardenafil, a selective PDE5 inhibitor, did not have the same effect. In the presence of CCh, CGA increased cyclic adenosine monophosphate (cAMP) level, whereas SQ22536 inhibited the increase of cAMP levels. Moreover, higher cAMP levels were obtained with CGA plus IBMX treatment than the total cAMP levels obtained with separate CGA and IBMX treatments. In conclusion, these results suggest that CGA inhibited CCh-induced contraction of mouse urinary bladder by partly increasing cAMP levels via adenylyl cyclase activation. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Mechanisms of hypoxia-induced cerebrovascular dilation in the newborn pig.

PubMed

Leffler, C W; Smith, J S; Edrington, J L; Zuckerman, S L; Parfenova, H

1997-03-01

The hypothesis that endothelium-dependent components contribute to the cerebromicrovascular dilation to hypoxia in the newborn pig was addressed. Piglets anesthetized with ketamine-acepromazine and maintained on alpha-chloralose were equipped with closed cranial windows. Injury to the endothelium of pial arterioles was produced by light activation of fluorescein dye. Light/dye injury reduced the pial arteriolar dilation to hypoxia (5 min, arterial PO2 approximately 30 mmHg) from 57 +/- 9 to 19 +/- 5%. Light/dye injury abolished the pial arteriolar dilation to hypercapnia but did not affect dilation to sodium nitroprusside. The pial arteriolar dilation to hypoxia was not affected by tetrodotoxin, N(omega)-nitro-L-arginine, glibenclamide, iberiotoxin, charybdotoxin, tetraethylammonium, or 8-phenyltheophylline. Hypoxia caused increases in the cerebral cortical production of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate. Cerebral vasodilation to hypoxia was inhibited by 5,8,11,14-eicosatetraynoic acid but was not greatly affected by cyclooxygenase or lipoxygenase inhibitors. In contrast, the cytochrome P-450 epoxygenase inhibitor miconazol decreased cerebral vasodilation to hypoxia from 45 +/- 5 to 17 +/- 4%. Therefore, the vascular endothelium appears to participate in cerebral microvascular dilation to hypoxia in newborn pigs. The mechanism may include cytochrome P-450 epoxygenase metabolites of arachidonic acid.

Protein kinase and phosphatase modulation of quail brain GABA(A) and non-NMDA receptors co-expressed in Xenopus oocytes.

PubMed

Moon, C; Fraser, S P; Djamgoz, M B

2000-02-01

The GABA(A) receptor and the non-NMDA subtype of the ionotropic glutamate receptor were co-expressed in Xenopus oocytes by injection of quail brain mRNA. The oocytes were treated with various protein kinase (PK) and protein phosphatase (PP) activators and inhibitors and the effects on receptor functioning were monitored. Two phorbol esters, 4-beta-phorbol 12-myristate-13-acetate (PMA) and 4-beta-phorbol 12,13-dibutyrate (PDBu); the cGMP-dependent PK activators sodium nitroprusside (SNP) and S-nitrosoglutathione (SNOG); and the PP inhibitor okadaic acid (OA) reduced the amplitude of the GABA-induced currents, whilst the PK inhibitor staurosporine potentiated it. In addition, PMA, PDBu, SNP, and OA reduced the desensitization of the GABA-induced response. Identical treatments generally had similar but less pronounced effects on responses generated by kainate (KA) but the desensitization characteristic of the non-NMDA receptor was not affected. None of the treatments had any effect on the reversal potentials of the induced currents. Immunoblots revealed that the oocytes express endogenous PKG and guanylate cyclase. The results are discussed in terms of the molecular structures of GABA(A) and non-NMDA receptors and the potential functional consequences of phosphorylation/dephosphorylation.

Feed artery role in blood flow control to rat hindlimb skeletal muscles.

PubMed Central

Williams, D A; Segal, S S

1993-01-01

1. Vasomotor tone and reactivity were investigated in feed arteries of the extensor digitorum longus and soleus muscles. Feed arteries are located external to the muscle and give rise to the microcirculation within each muscle. Resting diameter was smaller in feed arteries of the soleus muscle. 2. Feed arteries of both muscles dilated to similar peak values with sodium nitroprusside. 3. Micropressure measurements demonstrated resistance to blood flow in the feed arteries supplying both muscles. Feed arteries supplying soleus muscle demonstrated greater resistance to blood flow compared to feed arteries of extensor digitorum longus muscle. 4. Greater resting tone and larger pressure drop for feed arteries of soleus muscle suggest greater range of flow control compared to feed arteries of extensor digitorum longus muscle. 5. In both muscles, feed artery diameter increased with muscle contraction (functional dilatation) and in response to transient ischaemia (reactive dilatation). The magnitude of these responses varied between muscles. 6. Feed arteries are active sites of blood flow control in extensor digitorum longus and soleus muscles of the rat. These muscles differ in fibre type and recruitment properties. Differences in feed artery reactivity may contribute to differences in blood flow between these muscles observed at rest and during exercise. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8246199

Memantine Inhibits α3β2-nAChRs-Mediated Nitrergic Neurogenic Vasodilation in Porcine Basilar Arteries

PubMed Central

Wu, Celeste Yin-Chieh; Chen, Po-Yi; Chen, Mei-Fang; Kuo, Jon-Son; Lee, Tony Jer-Fu

2012-01-01

Memantine, an NMDA receptor antagonist used for treatment of Alzheimer’s disease (AD), is known to block the nicotinic acetylcholine receptors (nAChRs) in the central nervous system (CNS). In the present study, we examined by wire myography if memantine inhibited α3β2-nAChRs located on cerebral perivascular sympathetic nerve terminals originating in the superior cervical ganglion (SCG), thus, leading to inhibition of nicotine-induced nitrergic neurogenic dilation of isolated porcine basilar arteries. Memantine concentration-dependently blocked nicotine-induced neurogenic dilation of endothelium-denuded basilar arteries without affecting that induced by transmural nerve stimulation, sodium nitroprusside, or isoproterenol. Furthermore, memantine significantly inhibited nicotine-elicited inward currents in Xenopous oocytes expressing α3β2-, α7- or α4β2-nAChR, and nicotine-induced calcium influx in cultured rat SCG neurons. These results suggest that memantine is a non-specific antagonist for nAChR. By directly inhibiting α3β2-nAChRs located on the sympathetic nerve terminals, memantine blocks nicotine-induced neurogenic vasodilation of the porcine basilar arteries. This effect of memantine is expected to reduce the blood supply to the brain stem and possibly other brain regions, thus, decreasing its clinical efficacy in the treatment of Alzheimer’s disease. PMID:22792283

Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol.

PubMed

Neuman, Robert B; Hayek, Salim S; Poole, Joseph C; Rahman, Ayaz; Menon, Vivek; Kavtaradze, Nino; Polhemus, David; Veledar, Emir; Lefer, David J; Quyyumi, Arshed A

2016-03-01

Endothelial dysfunction is more prevalent in African Americans (AAs) compared with whites. The authors hypothesized that nebivolol, a selective β1 -antagonist that stimulates nitric oxide (NO), will improve endothelial function in AAs with hypertension when compared with metoprolol. In a double-blind, randomized, crossover study, 19 AA hypertensive patients were randomized to a 12-week treatment period with either nebivolol 10 mg or metoprolol succinate 100 mg daily. Forearm blood flow (FBF) was measured using plethysmography at rest and after intra-arterial infusion of acetylcholine and sodium nitroprusside to estimate endothelium-dependent and independent vasodilation, respectively. Physiologic vasodilation was assessed during hand-grip exercise. Measurements were repeated after NO blockade with L-N(G) -monomethylarginine (L-NMMA) and after inhibition of endothelium-derived hyperpolarizing factor (EDHF) with tetraethylammonium chloride (TEA). NO blockade with L-NMMA produced a trend toward greater vasoconstriction during nebivolol compared with metoprolol treatment (21% vs 12% reduction in FBF, P=.06, respectively). This difference was more significant after combined administration of L-NMMA and TEA (P<.001). Similarly, there was a contribution of NO to exercise-induced vasodilation during nebivolol but not during metoprolol treatment. There were significantly greater contributions of NO and EDHF to resting vasodilator tone and of NO to exercise-induced vasodilation with nebivolol compared with metoprolol in AAs with hypertension. © 2015 Wiley Periodicals, Inc.

Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol

PubMed Central

Neuman, Robert B.; Hayek, Salim; Poole, Joseph C.; Rahman, Ayaz; Menon, Vivek; Kavtaradze, Nino; Polhemus, David; Veledar, Emir; Lefer, David J.; Quyyumi, Arshed A.

2015-01-01

Endothelial dysfunction is more prevalent in African Americans (AA) compared to whites. We hypothesized that nebivolol, a selective β-1 antagonist that stimulates NO, will improve endothelial function in AA with hypertension when compared to metoprolol. In a double-blind, randomized, cross-over study, 19 AA hypertensive subjects were randomized to a 12-week treatment period with either nebivolol 10mg or metoprolol succinate 100mg daily. Forearm blood flow (FBF) was measured using plethysmography at rest and after intra-arterial infusion of acetylcholine, and sodium nitroprusside to estimate endothelium-dependent and independent vasodilation, respectively. Physiologic vasodilation was assessed during hand-grip exercise. Measurements were repeated after NO blockade with L-NG-monomethylarginine (L-NMMA), and after inhibition of endothelium-derived hyperpolarizing factor (EDHF) with tetraethylammonium chloride (TEA). NO blockade with L-NMMA produced a trend toward greater vasoconstriction during nebivolol compared to metoprolol treatment period (21% vs 12% reduction in FBF, p=0.06, respectively). This difference was more significant after combined administration of L-NMMA and TEA (p<0.001). Similarly, there was a contribution of NO to exercise-induced vasodilation during nebivolol but not during metoprolol treatment. There were significantly greater contributions of NO and EDHF to resting vasodilator tone and of NO to exercise-induced vasodilation with nebivolol compared to metoprolol in AA with hypertension. PMID:26285691

Involvement of nitric oxide in the jasmonate-dependent basal defense against root-knot nematode in tomato plants.

PubMed

Zhou, Jie; Jia, Feifei; Shao, Shujun; Zhang, Huan; Li, Guiping; Xia, Xiaojian; Zhou, Yanhong; Yu, Jingquan; Shi, Kai

2015-01-01

Jasmonic acid (JA) and nitric oxide (NO) are well-characterized signaling molecules in plant defense responses. However, their roles in plant defense against root-knot nematode (RKN, Meloidogyne incognita) infection are largely unknown. In this study, we found that the transcript levels of the JA- and NO-related biosynthetic and signaling component genes were induced after RKN infection. Application of exogenous JA and sodium nitroprusside (SNP; a NO donor) significantly decreased the number of egg masses in tomato roots after RKN infection and partially alleviated RKN-induced decreases in plant fresh weight and net photosynthetic rate. These molecules also alleviated RKN-induced increases in root electrolyte leakage and membrane peroxidation. Importantly, NO scavenger partially inhibited JA-induced RKN defense. The pharmacological inhibition of JA biosynthesis significantly increased the plants' susceptibility to RKNs, which was effectively alleviated by SNP application, showing that NO may be involved in the JA-dependent RKN defense pathway. Furthermore, both JA and SNP induced increases in protease inhibitor 2 (PI2) gene expression after RKN infestation. Silencing of PI2 compromised both JA- and SNP-induced RKN defense responses, suggesting that the PI2 gene mediates JA- and NO-induced defense against RKNs. This work will be important for deepening the understanding of the mechanisms involved in basal defense against RKN attack in plants.

Vascular wall function in insulin-resistant JCR:LA-cp rats: role of male and female sex.

PubMed

O'Brien, S F; Russell, J C; Dolphin, P J; Davidge, S T

2000-08-01

Vascular wall function was assessed in obese insulin-resistant (cp/cp) and lean normal (+/?), male and female, JCR:LA-cp rats. Both male and female cp/cp rats showed enhanced maximum contractility in response to norepinephrine; impaired smooth muscle in response to sodium nitroprusside, a nitric oxide (NO) donor; and impaired relaxation in response to acetylcholine (ACh), compared with their lean counterparts. The abnormalities were similar in male and female cp/cp rats. The NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), inhibited ACh-mediated relaxation significantly in male rats, both cp/cp and +/?. The inhibition of ACh-mediated relaxation by L-NAME in +/? females was less, with no reduction in maximal relaxation, and was absent in cp/cp females. These effects suggest that the relative importance of NO in the endothelial modulation of smooth muscle contractility is greater in male rats. The results are consistent with a decreased role for endothelial NO in the cp/cp rats of both sexes and a reduction in NO-independent cholinergic relaxation in the male cp/cp rat. This NO-independent mechanism is not affected in the female cp/cp rats. The relatively small differences between males and females in smooth muscle cell and vascular function may contribute to sex-related differences in the atherogenesis, vasospasm, and ischemic damage associated with the obese insulin-resistant state.

Effects of nitric oxide on expressions of nitrosocysteine and calcium-activated potassium channels in the supraoptic nuclei and neural lobe of dehydrated rats

PubMed Central

Kadekaro, Massako; Su, Guangxiao; Chu, Rong; Lei, Yongzhong; Li, Junfa; Fang, Li

2007-01-01

Nitric oxide (NO) is an important gas mediator in the signal transduction cascade regulating osmotic function in the hypothalamo-neurohypophysial system. We previously found that increased nitric oxide synthase (NOS) activity in the supraoptic nuclei (SON) and neural lobe following osmotic stimulation and NO could regulate the expression of Ca2+-activated K+ channel (BK channels) protein in the magnocellular system during dehydration. The aim of the current study is to examine the role of NO in the regulation of nitrosocysteine and BK channel protein in the magnocellular system in dehydrated animals. Using Western blot analysis and quantitative immunofluorescent staining study, we found that water deprivation in rats significantly enhanced the expression of nitrosocysteine protein in SON and neural lobes. Immunohistochemistry study indicated that dehydration significantly increased the profiles of SON neurons co-expressing nitrosocysteine with BK-channel protein. Intracerebroventricular administration of L-NAME (an inhibitor of NO synthase) significantly reduced the neuronal profiles of nitrosocysteine, as well as their co-expression with BK-channel in SON of dehydrated rats. However, treatment of sodium nitroprusside (a donor of NO) increased this co-expression. Our results indicate that NO signaling cascade may control the expression of BK channels through the regulation of nitrosocysteine in SON and neural lobe of rats during osmotic regulation. PMID:17098363

Predisposing factors for infantile urinary calculus in south-west of Iran.

PubMed

Alemzadeh-Ansari, Mohammad Hasan; Valavi, Ehsan; Ahmadzadeh, Ali

2014-01-01

Urinary calculi in infants are relatively infrequent, but their incidence has increased in the recent decades. The aim of this study was to investigate the clinical presentation, metabolic risk factors, and urinary tract abnormalities in infants suffering from kidney calculus. A total of 152 infants were admitted between 2009 and 2012 with ultrasonography-proven urolithiasis. A Foley catheter was fixed and 24-hour urine samples were analyzed for calcium, citrate, oxalate, uric acid, and magnesium. For detecting cystinuria, qualitative measurement of urinary cystine was done by nitroprusside test. Urinary tract structural abnormalities were also evaluated. The mean age at the diagnosis of kidney calculus was 5.46 months (range, 15 days to 12 months). The most common clinical findings were restlessness and urinary tract infection. A family history of calculi was found in 67.1% of the patients and 68.4% were born to consanguineous marriages. Metabolic abnormalities and urinary tract abnormalities were found in 96.1% and 15.1% of children, respectively. Urinary tract abnormalities were more common in girls. The most common metabolic risk factors were hypercalciuria (79.6%) and hypocitraturia (40.9%). Hyperoxaluria and hypomagnesuria were found in about 28% of patients, both of which were associated with bilateral urolithiasis. These findings show that urinary metabolic abnormalities are very common in infants with urolithiasis. Appropriate evaluation of urinary metabolic parameters can lead us to proper diagnosis and treatment.

Rescue therapy with Tanshinone IIA hinders transition of acute kidney injury to chronic kidney disease via targeting GSK3β

PubMed Central

Jiang, Chunming; Zhu, Wei; Yan, Xiang; Shao, Qiuyuan; Xu, Biao; Zhang, Miao; Gong, Rujun

2016-01-01

Acute kidney injury (AKI) remains challenging for clinical practice and poses a risk of developing progressive chronic kidney disease (CKD) with no definitive treatment available yet. Tanshinone IIA, an active ingredient of Chinese herbal Salvia miltiorrhiza, has been widely used in Asia for the remarkable organoprotective activities. Its effect on established AKI, however, remains unknown. In mice with folic acid-induced AKI, delayed treatment with Tanshinone IIA, commenced early or late after injury, diminished renal expression of kidney injury markers, reduced apoptosis and improved kidney dysfunction, concomitant with mitigated histologic signs of AKI to CKD transition, including interstitial fibrosis and tubular atrophy, and with an ameliorated inflammatory infiltration in tubulointerstitium and a favored M2-skewed macrophage polarization. Mechanistically, Tanshinone IIA blunted glycogen synthase kinase (GSK)3β overactivity and hyperactivation of its downstream mitogen-activated protein kinases that are centrally implicated in renal fibrogenesis and inflammation. Inhibition of GSK3β is likely a key mechanism mediating the therapeutic activity of Tanshinone IIA, because sodium nitroprusside, a GSK3β activator, largely offset its renoprotective effect. In confirmatory studies, rescue treatment with Tanshinone IIA likewise ameliorated ischemia/reperfusion-induced kidney destruction in mice. Our data suggest that Tanshinone IIA represents a valuable treatment that improves post-AKI kidney salvage via targeting GSK3β. PMID:27857162

Anti-apoptotic mechanism of Bacoside rich extract against reactive nitrogen species induced activation of iNOS/Bax/caspase 3 mediated apoptosis in L132 cell line.

PubMed

Anand, T; Pandareesh, M D; Bhat, Pratiksha V; Venkataramana, M

2014-10-01

Nitric oxide is a highly reactive free radical gas that reacts with a wide range of bio-molecules to produce reactive nitrogen species and exerts nitrative stress. Bacopa monniera is a traditional folk and ayurvedic medicine known to alleviate a variety of disorders. Aim of the present study is to evaluate the protective propensity of Bacopa monniera extract (BME) through its oxido-nitrosative and anti-apoptotic mechanism to attenuate sodium nitroprusside (SNP)-induced apoptosis in a human embryonic lung epithelial cell line (L132). Our results elucidate that pre-treatment of L132 cells with BME ameliorates the mitochondrial and plasma membrane damage induced by SNP as evidenced by MTT and LDH leakage assays. BME pre-treatment inhibited NO generation by down-regulating inducible nitric oxide synthase expression. BME exhibited potent antioxidant activity by up-regulating the antioxidant enzymes. SNP-induced damage to cellular, nuclear and mitochondrial integrity was also restored by BME, which was confirmed by ROS estimation, comet assay and mitochondrial membrane potential assays respectively. BME pre-treatment efficiently attenuated the SNP-induced apoptotic biomarkers such as Bax, cytochrome-c and caspase-3, which orchestrate the proteolytic damage of the cell. By considering all these findings, we report that BME protects L132 cells against SNP-induced toxicity via its free radical scavenging and anti-apoptotic mechanism.

Chorionic plate arterial function is altered in maternal obesity

PubMed Central

Hayward, C.E.; Higgins, L.; Cowley, E.J.; Greenwood, S.L.; Mills, T.A.; Sibley, C.P.; Wareing, M.

2013-01-01

Objectives To characterise Chorionic Plate Artery (CPA) function in maternal obesity, and investigate whether leptin exposure reproduces the obese CPA phenotype in normal-BMI women. Study design CPA responses to the thromboxane-A2 mimetic U46619 (pre/post leptin incubation), to the nitric oxide donor sodium nitroprusside (SNP) and the occurrence of tone oscillations (pre/post leptin incubation) were assessed in 46 term placentas from women of normal (18.5–24.9) or obese (>30) Body Mass Index (BMI). Outcome measures Area Under the dose response Curve (AUC), maximum response (Vmax), sensitivity (EC50) to U46619 (pre/post leptin) and SNP; average vessel tone, oscillation amplitude and frequency (pre/post leptin). Results U46619 vasoconstriction was similar between BMI categories (p > 0.05), however vasodilatation to SNP was reduced in obesity (AUC p = 0.02, Vmaxp = 0.04) compared to normal-BMI women. Leptin incubation altered responses to U46619 in both normal-BMI (EC50 at 100 ng/ml leptin; p < 0.05) and obese women (AUC at 50 ng/ml; p < 0.05) but vasomotion was unaffected (p > 0.05). Conclusions Maternal obesity is associated with altered placental vascular function which may adversely affect placental oxygen and nutrient transport, placing the fetus at risk. Leptin incubation altered CPA vascular function but did not reproduce the obese phenotype. PMID:23360794

Dietary copper supplements modulate aortic superoxide dismutase, nitric oxide and atherosclerosis.

PubMed

Lamb, David J; Tickner, Michelle L; Hourani, Susanna M O; Ferns, Gordon A A

2005-08-01

The objective was to test the hypothesis that dietary copper inhibits atherosclerosis by inducing superoxide dismutase (SOD) and potentiating nitric oxide (NO). New Zealand White rabbits were fed either a cholesterol diet (n = 8) or a cholesterol diet containing 0.02% copper acetate (n = 8) for 13 weeks. We found that the intimal area was significantly smaller in the animals supplemented with copper (P < 0.005), although integrated plasma cholesterol levels were not significantly different. This was associated with a significant increase in aortic copper content (P < 0.05), SOD activity (P < 0.05) and Cu/Zn SOD mRNA (P < 0.05) and a significant decrease in nitrotyrosine content (P < 0.05). Furthermore, there was a positive correlation between aortic copper content and SOD activity (P < 0.005, R(2) = 0.83) and a negative correlation between aortic superoxide dimutase activity and nitrotyrosine content (P < 0.005, R(2) = 0.93). In organ bath experiments, the relaxation of precontracted carotid artery rings to calcium ionophore was greater in animals supplemented with copper. No difference in response to sodium nitroprusside was observed. These data suggest that in the cholesterol-fed rabbit, copper supplements inhibit the progression of atherosclerosis by increasing SOD expression, thereby reducing the interaction of NO with superoxide, and hence potentiating NO-mediated pathways that may protect against atherosclerosis.

Airway structure and function in Eisenmenger's syndrome.

PubMed

McKay, K O; Johnson, P R; Black, J L; Glanville, A R; Armour, C L

1998-10-01

The responsiveness of airways from patients with Eisenmenger's syndrome (n = 5) was compared with that in airways from organ donors (n = 10). Enhanced contractile responses to cholinergic stimulation were found in airways from patients with Eisenmenger's syndrome. The maximal responses to acetylcholine, carbachol, and parasympathetic nerve stimulation in airway tissue from these patients were 221%, 139%, and 152%, respectively, of the maximal responses obtained in donor tissue. Further, relaxation responses to isoproterenol and levocromakalim were absent (n = 2) or markedly impaired (n = 3) in airways from patients with Eisenmenger's syndrome. This attenuated relaxation response was nonspecific in that it was also absent after vasoactive intestinal peptide, sodium nitroprusside, papaverine, and electrical field application. These observations can most likely be explained by a decrease in intrinsic smooth muscle tone, as precontraction of airways revealed relaxation responses that were equivalent to those obtained in donor tissues. Morphometric analysis of tissues used for the functional studies revealed no differences in the airway dimensions (internal perimeter) or airway wall components (e.g., smooth muscle, cartilage) or total area to explain these observations. Although the mechanism for this observed decrease in intrinsic airway smooth muscle tone is not certain, it may be due to alteration in the substructure of the airway wall or, alternatively, may result from the continued release of depressant factors in the vicinity of the smooth muscle which permanently alters smooth muscle responsiveness.

A new NO donor failed to release NO and to induce relaxation in the rat basilar artery.

PubMed

Paulo, Michele; Rodrigues, Gerson J; da Silva, Roberto S; Bendhack, Lusiane M

2012-02-14

Nitric oxide (NO)-donors are pharmacologically active substances that in vivo or in vitro release NO. Their most common side effect is headache caused by cerebral vasodilatation. We previously demonstrated that the new NO-donor Ru(terpy)(bdq)NO](3+) (Terpy), synthesized in our laboratory, induces relaxation of rat aorta. This study aimed to verify the effect of Terpy and sodium nitroprusside (SNP) in basilar artery. We conducted vascular reactivity experiments on endothelium-denuded basilar rings. The concentrations of iron (Fe) and ruthenium (Ru) complex were analyzed in basilar artery lysates after incubation with NO donors by mass spectrometry. We also evaluated the NO released from SNP and Terpy by using confocal microscopy. Interestingly, Terpy did not induce relaxation of the basilar artery. SNP induced relaxation in a concentration-dependent way. NO donors cross the membrane of vascular smooth muscle and entered the cell. In spite of its permeability, Terpy did not release NO in the basilar artery. Otherwise, SNP released NO in the basilar artery cells cytoplasm. Taken together, our results demonstrate that the new NO donor (Terpy) failed to release NO and to induce relaxation in the basilar artery. The NO donor SNP induces vascular relaxation due to NO release in the vascular smooth muscle cells. Copyright © 2011 Elsevier B.V. All rights reserved.

Nitric oxide affects IL-6 expression in human peripheral blood mononuclear cells involving cGMP-dependent modulation of NF-κB activity.

PubMed

Siednienko, Jakub; Nowak, Joanna; Moynagh, Paul N; Gorczyca, Wojciech A

2011-06-01

Interleukin 6 (IL-6) and nitric oxide (NO) are important mediators of the inflammatory response. We report that in human peripheral blood mononuclear cells (PBMCs), NO exerts a biphasic effect on the expression of IL-6. Using sodium nitroprusside (SNP) and S-nitrosoglutathione (GSNO) as NO-donating compounds, we observed that both mRNA and protein levels of IL-6 increased at lower (≤10μM) and decreased at higher (>100μM) concentrations of NO donors. Changes in the expression of IL-6 correlated with changes in the activity of NF-κB, which increased at lower and decreased at higher concentrations of both NO donors as shown by the electrophoretic mobility shift assay (EMSA). The effects of NO on NF-κB activity were cGMP-dependent because they were reversed in the presence of ODQ, the inhibitor of soluble guanylyl cyclase (sGC), and KT5823, the inhibitor of cGMP-dependent protein kinase (PKG). Moreover, the membrane permeable analog of cGMP (8-Br-cGMP) mimicked the effect of the NO donors. These observations show that NO, depending on its concentration, may act in human PBMCs as a stimulator of IL-6 expression involving the sGC/cGMP/PKG pathway. Copyright © 2011 Elsevier Ltd. All rights reserved.

Regulation of nitrate reductase by nitric oxide in Chinese cabbage pakchoi (Brassica chinensis L.).

PubMed

Du, Shaoting; Zhang, Yongsong; Lin, Xianyong; Wang, Yue; Tang, Caixian

2008-02-01

Nitrate reductase (NR), a committed enzyme in nitrate assimilation, involves generation of nitric oxide (NO) in plants. Here we show that the NR activity was significantly enhanced by the addition of NO donors sodium nitroprusside (SNP) and NONOate (diethylamine NONOate sodium) to the culturing solution, whereas it was decreased by NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (cPTIO). Interestingly, both NO gas and SNP directly enhanced but cPTIO inhibited the NR activities of crude enzyme extracts and purified NR enzyme. The cPTIO terminated the interaction between NR-generated NO and the NR itself. Furthermore, the NR protein content was not affected by the SNP treatment. The investigation of the partial reactions catalysed by purified NR using various electron donors and acceptors indicated that the haem and molybdenum centres in NR were the two sites activated by NO. The results suggest that the activation of NR activity by NO is regulated at the post-translational level, probably via a direct interaction mechanism. Accordingly, the concentration of nitrate both in leaves and roots was decreased after 2 weeks of cultivation with SNP. The present study identifies a new mechanism of NR regulation and nitrate assimilation, which provides important new insights into the complex regulation of N-metabolism in plants.

Attenuated baroreflex control of sympathetic nerve activity after cardiovascular deconditioning in rats

NASA Technical Reports Server (NTRS)

Moffitt, J. A.; Foley, C. M.; Schadt, J. C.; Laughlin, M. H.; Hasser, E. M.

1998-01-01

The effect of cardiovascular deconditioning on baroreflex control of the sympathetic nervous system was evaluated after 14 days of hindlimb unloading (HU) or the control condition. Rats were chronically instrumented with catheters and sympathetic nerve recording electrodes for measurement of mean arterial pressure (MAP) and heart rate (HR) and recording of lumbar (LSNA) or renal (RSNA) sympathetic nerve activity. Experiments were conducted 24 h after surgery, with the animals in a normal posture. Baroreflex function was assessed using a logistic function that related HR and LSNA or RSNA to MAP during infusion of phenylephrine and nitroprusside. Baroreflex influence on HR was not affected by HU. Maximum baroreflex-elicited LSNA was significantly reduced in HU rats (204 +/- 11.9 vs. 342 +/- 30.6% baseline LSNA), as was maximum reflex gain (-4.0 +/- 0.6 vs. -7.8 +/- 1.3 %LSNA/mmHg). Maximum baroreflex-elicited RSNA (259 +/- 10.8 vs. 453 +/- 28.0% baseline RSNA), minimum baroreflex-elicited RSNA (-2 +/- 2.8 vs. 13 +/- 4.5% baseline RSNA), and maximum gain (-5.8 +/- 0.5 vs. -13.6 +/- 3.1 %RSNA/mmHg) were significantly decreased in HU rats. Results demonstrate that baroreflex modulation of sympathetic nervous system activity is attenuated after cardiovascular deconditioning in rodents. Data suggest that alterations in the arterial baroreflex may contribute to orthostatic intolerance after a period of bedrest or spaceflight in humans.

Hydroxy-oleic acid, but not oleic acid, inhibits pharmacologic ...

EPA Pesticide Factsheets

Oleic acid (OA) and other fatty acids can become abundant in the systemic circulation after air pollution exposure as endogenously released lipolysis byproducts or by entering the body as a component of air pollution. Vascular damage has been observed with OA infusion, but it is not yet established whether increased circulating OA is able to produce the type of adverse cardiovascular effects associated with exposure to air pollution, or the mechanisms involved with such damage. Based on responses observed upon exposure of cultured endothelial cells, we hypothesized that OA and a hydroxylated metabolite (12-OH OA) would increase vascular tissue injury and impair vascular reactivity. Thoracic descending aorta tissue was collected from male Wistar Kyoto rats, aged 13-16 weeks. Prior to reactivity testing, independent LDH assays were performed with aortic rings to establish a subcytotoxic OA dose. To determine changes in vascular reactivity, aortic ring segments (n=3-4) were exposed for 1 hr to 100 µM OA, 12-OH OA, or an equivalent EtOH vehicle, followed by testing using myography and pharmacologic agents. Only 12-OH OA exposure significantly inhibited acetylcholine-induced endothelium-dependent vasorelaxation in aortic ring segments (25-30% reduction relative to EtOH control), based on maximum relaxation and dose-response. No change was seen in smooth muscle sensitivity to an exogenous nitric oxide source, sodium nitroprusside. Maximum aortic contractile force ge

Ethanol extract of Piper longum L. attenuates gentamicin-induced hair cell loss in neonatal cochlea cultures.

PubMed

Du, Xiao Fei; Song, Jae-Jun; Hong, Seungug; Kim, Jihye

2012-06-01

Piper longum L. (PL), also as known as long pepper, a well-known spice and traditional medicine in Asia and Pacific islands, has been reported to exhibit wide spectrum activity including antioxidant activity. However, little information is available on its protective effect on gentamicin (GM) induced ototoxicity which is commonly regarded as being mediated by reactive oxygen species and reactive nitrogen species. This study was undertaken to investigate the protective effect of PL ethanol extract on gentamicin-induced hair cell loss in neonatal cochlea cultures. Cochlea cultures from postnatal day 2-3 mice were used for analysis of the protective effects of PL against gentamicin-induced hair cell loss by phalloidin staining. E. coil cultures were used to determine whether PL interferes with the antibiotic activity of GM. Nitric oxide (NO)-scavenging activity of PL was also measured in vitro. GM induced significant dose-dependent hair cell loss in cochlea cultures. However, without interfering with the antibiotic activity of GM, PL showed a significant and concentration-dependent protective effect against GM-induced hair cell loss, and hair cells retained their stereocilia well. In addition, PL expressed direct scavenging activity toward NO radical liberated within solution of sodium nitroprusside. These findings demonstrate the protective effect of PL on GM-induced hair cell loss in neonatal cochlea cultures, and suggest that it might be of therapeutic benefit for treatment of GM-induced ototoxicity.

Time course of vasodilatory responses in skeletal muscle arterioles: role in hyperemia at onset of exercise

NASA Technical Reports Server (NTRS)

Wunsch, S. A.; Muller-Delp, J.; Delp, M. D.

2000-01-01

At the onset of dynamic exercise, muscle blood flow increases within 1-2 s. It has been postulated that local vasodilatory agents produced by the vascular endothelium or the muscle itself contribute to this response. We hypothesized that only vasodilators that act directly on the vascular smooth muscle could produce vasodilation of skeletal muscle arterioles in <2 s. To test this hypothesis, we determined the time course of the vasodilatory response of isolated skeletal muscle arterioles to direct application of potassium chloride, adenosine, acetylcholine, and sodium nitroprusside. Soleus and gastrocnemius muscles were dissected from the hindlimbs of male Sprague-Dawley rats. First-order arterioles (100-200 microm) were isolated, cannulated on micropipettes, and pressurized to 60 cmH(2)O in an organ bath. Vasodilatory agents were added directly to the bath, and diameter responses of the arterioles were recorded in real time on a videotape recorder. Frame-by-frame analysis of the diameter responses indicated that none of the vasodilator agents tested produced significant diameter increases in <4 s in either soleus or gastrocnemius muscle arterioles. These results indicate that, although these local vasodilators produce significant vasodilation of skeletal muscle resistance arterioles, these responses are not rapid enough (within 1-2 s) to contribute to the initiation of the exercise hyperemic response at the onset of dynamic exercise.

High-fat feeding reduces endothelium-dependent vasodilation in rats: differential mechanisms for saturated and unsaturated fatty acids?

PubMed

Song, Guang-Yao; Gao, Yu; Di, Yu-Wei; Pan, Li-Li; Zhou, Yu; Ye, Ji-Ming

2006-08-01

1. Chronic feeding with a high-fat diet can cause metabolic syndrome in rodents similar to humans, but the role of saturated versus unsaturated fats in vascular tension remains unclear. 2. The present study shows that rats on a diet rich in either saturated or unsaturated fat had higher blood pressure compared with chow-fed rats (approximately 130 vs 100 mmHg, respectively), along with hyperlipidaemia and insulin resistance. Compared with responses of phenylephrine-preconstricted artery segments from chow-fed rats, vasorelaxation of isolated renal arteries from high-fat fed rats was reduced substantially (> 50%) in response to acetylcholine (0.01-10 micromol/L) and moderately to nitroprusside (>or=1 micromol/L) at low concentrations. Acetylcholine-induced vasorelaxation of arteries from high-fat fed rats was also more sensitive to inhibition by the nitric oxide (NO) synthase inhibitors NG-nitro-L-arginine and methylene blue. 3. In human umbilical vein endothelial cells, the production of NO and endothelin-1 was significantly inhibited by unsaturated fatty acids. In comparison, saturated fatty acids stimulated endothelin-1 production without altering NO production. 4. The data indicate that both saturated and unsaturated high-fat feeding may result in an increase in blood pressure owing to reduced endothelium-dependent vasorelaxation in the arterial system. The impaired endothelium-dependent vasorelaxation induced by saturated and unsaturated fatty acids may involve different mechanisms.

Data set characterizing the systemic alterations of microvascular reactivity and capillary density, in patients presenting with infective endocarditis.

PubMed

Tibirica, Eduardo; Barcelos, Amanda; Lamas, Cristiane

2018-06-01

This article represents data associated with a prior publication from our research group, under the title: Evaluation of microvascular endothelial function and capillary density in patients with infective endocarditis using laser speckle contrast imaging and video-capillaroscopy [1]. Patients with definite infective endocarditis, under stable clinical conditions, were prospectively included. The clinical and laboratory features are presented for each of them in raw form. Microvascular reactivity was evaluated using a laser speckle contrast imaging (LSCI) system with a laser wavelength of 785 nm. LSCI was used in combination with the iontophoresis of acetylcholine (ACh) or sodium nitroprusside (SNP) for the noninvasive, continuous measurement of cutaneous microvascular perfusion changes in arbitrary perfusion units (APU). The images were analyzed using the manufacturer's software. One skin site on the ventral surface of the forearm was chosen for the experiment. Microvascular reactivity was also evaluated using post-occlusive reactive hyperemia, whereby arterial occlusion was achieved with supra-systolic pressure (50 mmHg above the systolic arterial pressure) using a sphygmomanometer for three minutes. Following the release of pressure, maximum flux was measured. Data on cutaneous microvascular density were obtained using intravital video-capillaroscopy. The data obtained may be helpful by showing the usefulness of laser-based noninvasive techniques in systemic infectious diseases other than sepsis, in different clinical settings and countries.

Effects of Chronic Nitric Oxide Synthase Inhibition on Endothelium-Dependent and -Independent Relaxation in Arteries that Perfuse Skeletal Muscle of Swine

PubMed Central

Newcomer, S.C.; Taylor, J.C.; McAllister, R.M.; Laughlin, M.H.

2012-01-01

The purpose of this investigation was to test the hypothesis that chronic L-NAME treatment produces differential effects on conduit artery and resistance arteriole relaxation responses to endothelium-dependent and –independent vasodilators in arteries that perfuse skeletal muscle of swine. To test this hypothesis conduit skeletal muscle arteries and second order skeletal muscle arterioles were harvested from 14 Yucatan swine that were chronically administered L-NAME and 16 controls. In vitro assessments of vasorelaxation to increasing doses of acetylcholine (ACH), bradykinin (BK), and sodium nitroprusside (SNP) were performed in both conduit and 2A arterioles. L-NAME treatment produced a significant reduction in both BK and ACH relaxation responses in the conduit arteries. In contrast, the relaxation response and/or sensitivity to SNP were significantly greater in the intact, but not denuded, conduit arterial rings from chronically L-NAME treated swine. There were no significant effects of chronic L-NAME treatment on vasodilation of skeletal muscle arterioles. These findings suggest: (1) that unlike arterioles, skeletal muscle conduit arteries do not functionally compensate for a lack of NO through the upregulation of alternative vasodilator pathways. (2) that the greater relaxation response in conduit arteries of chronically L-NAME treated swine to SNP can be explained by alterations to the endothelium. PMID:18568942

Triiodothyronine Potentiates Vasorelaxation via PKG/VASP Signaling in Vascular Smooth Muscle Cells.

PubMed

Samuel, Sherin; Zhang, Kuo; Tang, Yi-Da; Gerdes, A Martin; Carrillo-Sepulveda, Maria Alicia

2017-01-01

Vascular relaxation caused by Triiodothyronine (T3) involves direct activation of endothelial cells (EC) and vascular smooth muscle cells (VSMC). Activation of protein kinase G (PKG) has risen as a novel contributor to the vasorelaxation mechanism triggered by numerous stimuli. We hypothesize that T3-induced vasorelaxation involves PKG/vasodilator-stimulated phosphoprotein (VASP) signaling pathway in VSMC. Human aortic endothelial cells (HAEC) and VSMC were treated with T3 for short (2 to 60 minutes) and long term (24 hours). Nitric oxide (NO) production was measured using DAF-FM. Expression of protein targets was determined using western blot. For functional studies, rat aortas were isolated and treated with T3 for 20 minutes and mounted in a wire myograph. Relaxation was measured by a concentration-dependent response to acetylcholine (ACh) and sodium nitroprusside (SNP). Aortas stimulated with T3 exhibited augmented sensitivity to ACh and SNP-induced relaxation, endothelium-dependent and endothelium-independent responses, respectively. T3 directly increased vasorelaxation, which was abolished in the presence of a PKG inhibitor. T3 markedly induced phosphorylation of Akt, eNOS and consequently increased NO production in EC. Likewise, T3 induced phosphorylation of VASP at serine 239 via the PKG pathway in VSMC. Our findings have uncovered a PKG/VASP signaling pathway in VSMC as a key molecular mechanism underlying T3-induced vascular relaxation. © 2017 The Author(s)Published by S. Karger AG, Basel.

Dietary copper supplements modulate aortic superoxide dismutase, nitric oxide and atherosclerosis

PubMed Central

Lamb, David J; Tickner, Michelle L; Hourani, Susanna M O; Ferns, Gordon A A

2005-01-01

The objective was to test the hypothesis that dietary copper inhibits atherosclerosis by inducing superoxide dismutase (SOD) and potentiating nitric oxide (NO). New Zealand White rabbits were fed either a cholesterol diet (n = 8) or a cholesterol diet containing 0.02% copper acetate (n = 8) for 13 weeks. We found that the intimal area was significantly smaller in the animals supplemented with copper (P < 0.005), although integrated plasma cholesterol levels were not significantly different. This was associated with a significant increase in aortic copper content (P < 0.05), SOD activity (P < 0.05) and Cu/Zn SOD mRNA (P < 0.05) and a significant decrease in nitrotyrosine content (P < 0.05). Furthermore, there was a positive correlation between aortic copper content and SOD activity (P < 0.005, R2 = 0.83) and a negative correlation between aortic superoxide dimutase activity and nitrotyrosine content (P < 0.005, R2 = 0.93). In organ bath experiments, the relaxation of precontracted carotid artery rings to calcium ionophore was greater in animals supplemented with copper. No difference in response to sodium nitroprusside was observed. These data suggest that in the cholesterol-fed rabbit, copper supplements inhibit the progression of atherosclerosis by increasing SOD expression, thereby reducing the interaction of NO with superoxide, and hence potentiating NO-mediated pathways that may protect against atherosclerosis. PMID:16045547

Phosphodiesterase-3 inhibitor cilostazol reverses endothelial dysfunction with ageing in rat mesenteric resistance arteries.

PubMed

Moreira, Hicla S; Lima-Leal, Geórgia A; Santos-Rocha, Juliana; Gomes-Pereira, Leonardo; Duarte, Gloria P; Xavier, Fabiano E

2018-03-05

Ageing impairs endothelial function, which is considered a hallmark of the development of cardiovascular diseases in elderly. Cilostazol, a phosphodiesterase-3 inhibitor, has antiplatelet, antithrombotic and protective effects on endothelial cells. Here, we hypothesized that cilostazol could improve endothelial function in mesenteric resistance arteries (MRA) from old rats. Using eight-week cilostazol-treated (100mg/kg/day) or untreated 72-week-old Wistar rats, we evaluate the relaxation to acetylcholine, sodium nitroprusside (SNP), forskolin and isoproterenol and the noradrenaline-induced contraction in MRA. Superoxide anion and nitric oxide (NO) was measured by dihydroethidium- and diaminofluorescein-2-emitted fluorescence, respectively. Normotensive old rats had impaired acetylcholine-induced NO- and EDHF-mediated relaxation and increased noradrenaline vasoconstriction than young rats. This age-associated endothelial dysfunction was restored by cilostazol treatment. Relaxation to SNP, forskolin or isoproterenol remained unmodified by cilostazol. Diaminofluorescein-2-emitted fluorescence was increased while dihydroethidium-emitted was decreased by cilostazol, indicating increased NO and reduced superoxide generation, respectively. Cilostazol improves endothelial function in old MRA without affecting blood pressure. This protective effect of cilostazol could be attributed to reduced oxidative stress, increased NO bioavailability and EDHF-type relaxation. Although these results are preliminary, we believe that should stimulate further interest in cilostazol as an alternative for the treatment of age-related vascular disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Static magnetic field blood pressure buffering, baroreflex vs. vascular blood pressure control mechanism.

PubMed

Gmitrov, Juraj

2010-02-01

We compared the effect of static magnetic field (SMF) and verapamil, a potent vascular calcium channel blocking agent, on sudden elevation in blood pressure in conjunction with arterial baroreflex sensitivity (BRS) and microcirculation. Forty-four experiments were performed on conscious rabbits sedated using pentobarbital intravenous (i.v.) infusion (5 mg kg(-1) h(-1)). Mean femoral artery blood pressure (MAP), heart rate, BRS and ear lobe skin microcirculatory blood flow, estimated using microphotoelectric plethysmography (MPPG), were simultaneously measured after a 40 min exposure of the sinocarotid baroreceptors to 350 mT SMF, generated by Nd(2)-Fe(14)-B magnets, or 30 min of verapamil i.v. administration (20 microg kg(-1) min(-1)). BRS was assessed from heart rate and MAP responses to i.v. bolus of nitroprusside and phenylephrine. The decrease in phenylephrine-induced abrupt elevation in MAP (DeltaMAP(AE)) was significantly larger after verapamil than after SMF exposure. DeltaMAP(AE) inversely correlated with verapamil-induced significant increase in DeltaMPPG (r = 0.53, p < 0.000) and with SMF-induced significant increase in DeltaBRS (r = 0.47, p < 0.016). Our results suggest that verapamil-potentiated vascular blood pressure buffering mechanism was more effective than SMF-potentiated baroreflex-mediated blood pressure buffering mechanism, and a potential benefit of both approaches in cardiovascular conditions with abrupt high elevation in blood pressure.

Salicylic acid and nitric oxide alleviate high temperature induced oxidative damage in Lablab purpureus L plants by regulating bio-physical processes and DNA methylation.

PubMed

Rai, Krishna Kumar; Rai, Nagendra; Rai, Shashi Pandey

2018-07-01

Salicylic acid (SA) and sodium nitroprusside (SNP, NO donor) modulates plant growth and development processes and recent findings have also revealed their involvement in the regulation of epigenetic factors under stress condition. In the present study, some of these factors were comparatively studied in hyacinth bean plants subjected to high temperature (HT) environment (40-42 °C) with and without exogenous application of SA and SNP under field condition. Exogenous application of SA and SNP substantially modulated the growth and biophysical process of hyacinth bean plants under HT environment. Exogenous application of SA and SNP also remarkably regulated the activities of antioxidant enzymes, modulated mRNA level of certain enzymes, improves plant water relation, enhance photosynthesis and thereby increasing plant defence under HT. Coupled restriction enzyme digestion-random amplification (CRED-RA) technique revealed that many methylation changes were "dose dependent" and HT significantly increased DNA damages as evidenced by both increase and decrease in bands profiles, methylation and de-methylation pattern. Thus, the result of the present study clearly shows that exogenous SA and SNP regulates DNA methylation pattern, modulates stress-responsive genes and can impart transient HT tolerance by synchronizing growth and physiological acclimatization of plants, thus narrowing the gaps between physio-biochemical and molecular events in addressing HT tolerance. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Agmatine ameliorates atherosclerosis progression and endothelial dysfunction in high cholesterol-fed rabbits.

PubMed

El-Awady, Mohammed S; Suddek, Ghada M

2014-06-01

The aim of this work was to explore possible effects of agmatine, an endogenous inhibitor of inducible nitric oxide synthase (iNOS), against hypercholesterolemia-induced lipid profile changes and endothelial dysfunction. Hypercholesterolemia was induced by feeding rabbits with a high-cholesterol diet (HCD, 0.5%) for 8 weeks. Another HCD-fed group was orally administered agmatine (10 mg/kg/day) during weeks 5 through 8. Serum lipid profile, malondialdehyde (MDA), nitric oxide (NO) and lactate dehydrogenase (LDH) were determined. Aorta was isolated to analyse vascular reactivity, atherosclerotic lesions and intima/media (I/M) ratio. HCD induced a significant increase in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides and high-density lipoprotein cholesterol (HDL-C). Agmatine administration significantly decreased HCD-induced elevations in serum TC and LDL-C, MDA, LDH and NO while significantly increased HDL-C levels. Additionally, agmatine significantly protected against HCD-induced attenuation of rabbit aortic endothelium-dependent relaxation to acetylcholine. HCD and agmatine did not significantly influence aortic endothelium-independent relaxation to sodium nitroprusside. Moreover, agmatine significantly reduced the elevation in aortic atherosclerotic lesion area and I/M ratio. This study is the first to reveal that agmatine has the ability to ameliorate hypercholesterolemia-induced lipemic-oxidative and endothelial function injuries possibly by its antioxidant potential and/or iNOS inhibition. © 2014 Royal Pharmaceutical Society.

The Dynamics of the Defense Strategy of Pea Induced by Exogenous Nitric Oxide in Response to Aphid Infestation

PubMed Central

Woźniak, Agnieszka; Formela, Magda; Bilman, Piotr; Grześkiewicz, Katarzyna; Bednarski, Waldemar; Marczak, Łukasz; Narożna, Dorota; Dancewicz, Katarzyna; Mai, Van Chung; Borowiak-Sobkowiak, Beata; Floryszak-Wieczorek, Jolanta; Gabryś, Beata; Morkunas, Iwona

2017-01-01

The aim of this study was to investigate the effect of exogenous nitric oxide (NO), i.e., S-nitrosoglutathione (GSNO) and sodium nitroprusside (SNP), on the metabolic status of Pisum sativum L. cv. Cysterski leaves infested by Acyrthosiphon pisum Harris, population demographic parameters and A. pisum feeding activity. A reduction in the level of semiquinone radicals in pea seedling leaves pretreated with exogenous NO occurred 24 h after A. pisum infestation, which was earlier than in non-pretreated leaves. A decrease in the level of O2•− was observed in leaves pretreated with GSNO and infested by aphids at 48 and 72 h post-infestation (hpi). Directly after the pretreatment with GSNO, an increase in the level of metal ions was recorded. NO considerably induced the relative mRNA levels for phenylalanine ammonia-lyase in 24-h leaves pretreated with NO donors, both non-infested and infested. NO stimulated the accumulation of pisatin in leaves until 24 h. The Electrical Penetration Graph revealed a reduction in the feeding activity of the pea aphid on leaves pretreated with NO. The present study showed that foliar application of NO donors induced sequentially defense reactions of pea against A. pisum and had a deterrent effect on aphid feeding and limited the population growth rate. PMID:28165429

Impaired pulmonary artery contractile responses in a rat model of microgravity: role of nitric oxide

NASA Technical Reports Server (NTRS)

Nyhan, Daniel; Kim, Soonyul; Dunbar, Stacey; Li, Dechun; Shoukas, Artin; Berkowitz, Dan E.

2002-01-01

Vascular contractile hyporesponsiveness is an important mechanism underlying orthostatic intolerance after microgravity. Baroreceptor reflexes can modulate both pulmonary resistance and capacitance function and thus cardiac output. We hypothesized, therefore, that pulmonary vasoreactivity is impaired in the hindlimb-unweighted (HLU) rat model of microgravity. Pulmonary artery (PA) contractile responses to phenylephrine (PE) and U-46619 (U4) were significantly decreased in the PAs from HLU vs. control (C) animals. N(G)-nitro-L-arginine methyl ester (10(-5) M) enhanced the contractile responses in the PA rings from both C and HLU animals and completely abolished the differential responses to PE and U4 in HLU vs. C animals. Vasorelaxant responses to ACh were significantly enhanced in PA rings from HLU rats compared with C. Moreover, vasorelaxant responses to sodium nitroprusside were also significantly enhanced. Endothelial nitric oxide synthase (eNOS) and soluble guanlyl cyclase expression were significantly enhanced in PA and lung tissue from HLU rats. In marked contrast, the expression of inducible nitric oxide synthase was unchanged in lung tissue. These data support the hypothesis that vascular contractile responsiveness is attenuated in PAs from HLU rats and that this hyporesponsiveness is due at least in part to increased nitric oxide synthase activity resulting from enhanced eNOS expression. These findings may have important implications for blood volume distribution and attenuated stroke volume responses to orthostatic stress after microgravity exposure.

N-acetylcysteine does not improve the endothelial and smooth muscle function in the human saphenous vein.

PubMed

Sharif, Muhammad Anees; Bayraktutan, Ulvi; Young, Ian Stuart; Soong, Chee Voon

2007-01-01

Oxidative stress can lead to vein graft dysfunction in the saphenous vein. This ex vivo study is aimed to compare the effects of increasing concentrations of the antioxidant N-acetylcysteine (NAC) with heparinized saline (HS) on endothelial and smooth muscle function in the human saphenous vein. Long saphenous vein segment obtained during infrainguinal bypass surgery was divided into 7 rings; 1 immersed in HS and the remaining 6 in increasing NAC concentrations (0.0025%, 0.005%, 0.01%, 0.02%, 0.03%, and 0.04%). Rings were mounted in an organ bath, and relaxant responses to acetylcholine and sodium nitroprusside were assessed through isometric tension studies. Endothelium-dependent relaxations were observed in 77 vein segments from 11 patients. No significant difference was seen in veins treated with either lower NAC concentrations (0.0025%, 0.005%, 0.01%, 0.02%, and 0.03%) or HS. However, HS-treated veins showed significantly better relaxation compared to those treated with maximum (0.04%) NAC (P < .05). Endothelium-independent relaxations were observed in 91 segments from 13 patients. No difference in relaxation was observed between veins treated with HS or any of the NAC concentrations. In conclusion, lower NAC concentrations do not offer better endothelial protection than HS, whereas the highest NAC concentration has a detrimental effect on endothelium-dependent relaxation. Moreover, NAC did not show beneficial effect on direct smooth muscle relaxation.

Acute effects of coffee on skin blood flow and microvascular function.

PubMed

Tesselaar, Erik; Nezirevic Dernroth, Dzeneta; Farnebo, Simon

2017-11-01

Studies on the acute effects of coffee on the microcirculation have shown contradicting results. This study aimed to investigate if intake of caffeine-containing coffee changes blood flow and microvascular reactivity in the skin. We measured acute changes in cutaneous vascular conductance (CVC) in the forearm and the tip of the finger, the microvascular response to transdermal iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) and post-occlusive reactive hyperemia (PORH) in the skin, after intake of caffeinated or decaffeinated coffee. Vasodilatation during iontophoresis of ACh was significantly stronger after intake of caffeinated coffee compared to after intake of decaffeinated coffee (1.26±0.20PU/mmHg vs. 1.13±0.38PU/mmHg, P<0.001). Forearm CVC before and after PORH were not affected by caffeinated and decaffeinated coffee. After intake of caffeinated coffee, a more pronounced decrease in CVC in the fingertip was observed compared to after intake of decaffeinated coffee (-1.36PU/mmHg vs. -0.52PU/mmHg, P=0.002). Caffeine, as ingested by drinking caffeinated coffee acutely improves endothelium-dependent microvascular responses in the forearm skin, while endothelium-independent responses to PORH and SNP iontophoresis are not affected. Blood flow in the fingertip decreases markedly during the first hour after drinking caffeinated coffee compared to decaffeinated coffee. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of N-methyl-D-aspartate receptors and nitric oxide in cochlear dopamine release.

PubMed

Halmos, G; Horváth, T; Polony, G; Fekete, A; Kittel, A; Vizi, E S; van der Laan, B F A M; Zelles, T; Lendvai, B

2008-06-23

Dopamine (DA) released from lateral olivocochlear (LOC) terminals may have a neuroprotective effect in the cochlea. To explore the role of N-methyl-d-aspartate (NMDA) receptors and nitric oxide (NO) in the modulation of a cochlear DA release, we measured the release of [3H]DA from isolated mouse cochlea in response to the application of NMDA. NMDA at 100 muM significantly increased the electrical-field stimulation-evoked and resting release of DA from the cochlea. The NO donor sodium nitroprusside enhanced the basal outflow of DA but failed to influence the evoked release. The administration of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) alone was ineffective, but it significantly inhibited the initial phase of the NMDA-induced elevation of DA outflow, which suggested the role of NO in the NMDA-induced DA release. The DA uptake inhibitor nomifensine increased the electrically evoked release of DA. Nomifensine failed to change the effect of NMDA on the resting or electrically-evoked DA release, which suggested that the uptake mechanism does not play a role in NMDA-evoked and NO-mediated DA release. In summary, we provide evidence that NO can modulate the release of DA from the cochlea following NMDA receptor activation, but does not affect the uptake of DA.

Nitric oxide protects carbon assimilation process of watermelon from boron-induced oxidative injury.

PubMed

Farag, Mohamed; Najeeb, Ullah; Yang, Jinghua; Hu, Zhongyuan; Fang, Zhang Ming

2017-02-01

Nitric oxide (NO) mediates plant response to a variety of abiotic stresses; however, limited information is available on its effect on boron (B)-stressed watermelon plants. The present study investigates the mechanism through which NO protects watermelon seedlings from B deficiency and toxicity stresses. Five days old watermelon seedlings were exposed to B (0, 0.5 and 10 mg L -1 ) alone or with 75 μmole of NO donor sodium nitroprusside (SNP) for 30 days. Both low and high B concentrations in the media altered nutrient accumulation and impaired various physiological processes of watermelon seedlings, leading to a significant reduction in biomass production. The plants exposed to B deficient or toxic concentrations had 66 and 69% lower shoot dry weight, respectively compared with optimum B levels. B toxicity-induced growth inhibition of watermelon seedlings was associated with high B translocation to shoot tissues, which caused lipid membrane peroxidation (12% increase) and chlorophyll destruction (25% reduction). In contrast, B deficiency accelerated generation of reactive oxygen species (ROS), specifically OH -1 and induced cellular oxidative injury. Exogenously applied SNP promoted leaf chlorophyll, photosynthesis and consequently biomass production in B-stressed watermelon seedlings by reducing B accumulation, lipid membrane peroxidation and ROS generation. It also activated antioxidant enzymes such as SOD, POD and APX, and protected the seedlings from ROS-induced cellular burst. Copyright © 2016. Published by Elsevier Masson SAS.

Involvement of nitric oxide in the jasmonate-dependent basal defense against root-knot nematode in tomato plants

PubMed Central

Zhou, Jie; Jia, Feifei; Shao, Shujun; Zhang, Huan; Li, Guiping; Xia, Xiaojian; Zhou, Yanhong; Yu, Jingquan; Shi, Kai

2015-01-01

Jasmonic acid (JA) and nitric oxide (NO) are well-characterized signaling molecules in plant defense responses. However, their roles in plant defense against root-knot nematode (RKN, Meloidogyne incognita) infection are largely unknown. In this study, we found that the transcript levels of the JA- and NO-related biosynthetic and signaling component genes were induced after RKN infection. Application of exogenous JA and sodium nitroprusside (SNP; a NO donor) significantly decreased the number of egg masses in tomato roots after RKN infection and partially alleviated RKN-induced decreases in plant fresh weight and net photosynthetic rate. These molecules also alleviated RKN-induced increases in root electrolyte leakage and membrane peroxidation. Importantly, NO scavenger partially inhibited JA-induced RKN defense. The pharmacological inhibition of JA biosynthesis significantly increased the plants’ susceptibility to RKNs, which was effectively alleviated by SNP application, showing that NO may be involved in the JA-dependent RKN defense pathway. Furthermore, both JA and SNP induced increases in protease inhibitor 2 (PI2) gene expression after RKN infestation. Silencing of PI2 compromised both JA- and SNP-induced RKN defense responses, suggesting that the PI2 gene mediates JA- and NO-induced defense against RKNs. This work will be important for deepening the understanding of the mechanisms involved in basal defense against RKN attack in plants. PMID:25914698

Impairment of the vascular relaxation and differential expression of caveolin-1 of the aorta of diabetic +db/+db mice.

PubMed

Lam, Tze Yan; Seto, Sai Wang; Lau, Yee Man; Au, Lai Shan; Kwan, Yiu Wa; Ngai, Sai Ming; Tsui, Kwong Wing

2006-09-28

In this study, we compared the endothelium-dependent and -independent relaxation of the isolated thoracic aorta of control (+db/+m) and diabetic (+db/+db) (C57BL/KsJ) mice. The gene expression (mRNA and protein) level of the muscarinic M(3) receptors, endothelial nitric oxide synthase (eNOS) and caveolin-1 of the aorta was also evaluated. Acetylcholine caused a concentration-dependent, N(G)-nitro-L-arginine methyl-ester (20 microM)-sensitive relaxation, with approximately 100% relaxation at 10 microM, in +db/+m mice. In +db/+db mice, the acetylcholine-induced relaxation was significantly smaller (maximum relaxation: approximately 80%). The sodium nitroprusside-mediated relaxation was slightly diminished in +db/+db mice, compared to +db/+m mice. However, there was no significant difference in the isoprenaline- and cromakalim-induced relaxation observed in both species. The mRNA and protein expression levels of caveolin-1 were significantly higher in the aorta of +db/+db mice. In contrast, there was no difference in the mRNA and protein expression levels of eNOS and muscarinic M(3) receptors between these mice. Our results demonstrate that the impairment of the acetylcholine-induced, endothelium-dependent aortic relaxation observed in +db/+db mice was probably associated with an enhanced expression of caveolin-1 mRNA and protein.

SOD1 Overexpression Preserves Baroreflex Control of Heart Rate with an Increase of Aortic Depressor Nerve Function

PubMed Central

Hatcher, Jeffrey; Gu, He; Cheng, Zixi (Jack)

2016-01-01

Overproduction of reactive oxygen species (ROS), such as the superoxide radical (O2 ∙−), is associated with diseases which compromise cardiac autonomic function. Overexpression of SOD1 may offer protection against ROS damage to the cardiac autonomic nervous system, but reductions of O2 ∙− may interfere with normal cellular functions. We have selected the C57B6SJL-Tg (SOD1)2 Gur/J mouse as a model to determine whether SOD1 overexpression alters cardiac autonomic function, as measured by baroreflex sensitivity (BRS) and aortic depressor nerve (ADN) recordings, as well as evaluation of baseline heart rate (HR) and mean arterial pressure (MAP). Under isoflurane anesthesia, C57 wild-type and SOD1 mice were catheterized with an arterial pressure transducer and measurements of HR and MAP were taken. After establishing a baseline, hypotension and hypertension were induced by injection of sodium nitroprusside (SNP) and phenylephrine (PE), respectively, and ΔHR versus ΔMAP were recorded as a measure of baroreflex sensitivity (BRS). SNP and PE treatment were administered sequentially after a recovery period to measure arterial baroreceptor activation by recording aortic depressor nerve activity. Our findings show that overexpression of SOD1 in C57B6SJL-Tg (SOD1)2 Gur/J mouse preserved the normal HR, MAP, and BRS but enhanced aortic depressor nerve function. PMID:26823951

Exogenous NO administration and alpha-adrenergic vasoconstriction in human limbs.

PubMed

Rosenmeier, Jaya B; Fritzlar, Sandy J; Dinenno, Frank A; Joyner, Michael J

2003-12-01

Nitric oxide (NO) is capable of blunting alpha-adrenergic vasoconstriction in contracting skeletal muscles of experimental animals (functional sympatholysis). We therefore tested the hypothesis that exogenous NO administration can blunt alpha-adrenergic vasoconstriction in resting human limbs by measuring forearm blood flow (FBF; Doppler ultrasound) and blood pressure in eight healthy males during brachial artery infusions of three alpha-adrenergic constrictors (tyramine, which evokes endogenous norepinephrine release; phenylephrine, an alpha1-agonist; and clonidine, an alpha2-agonist). To simulate exercise hyperemia, the vasoconstriction caused by the alpha-agonists was compared during adenosine-mediated (>50% NO independent) and sodium nitroprusside-mediated (SNP; NO donor) vasodilation of the forearm. Both adenosine and SNP increased FBF from approximately 35-40 to approximately 200-250 ml/min. All three alpha-adrenergic constrictor drugs caused marked reductions in FBF and calculated forearm vascular conductance (P < 0.05). The relative reductions in forearm vascular conductance caused by the alpha-adrenergic constrictors during SNP infusion were similar (tyramine, -74 +/- 3 vs. -65 +/- 2%; clonidine, -44 +/- 6 vs. -44 +/- 6%; P > 0.05) or slightly greater (phenylephrine, -47 +/- 6 vs. -33 +/- 6%; P < 0.05) compared with the responses during adenosine. In conclusion, these results indicate that exogenous NO sufficient to raise blood flow to levels simulating those seen during exercise does not blunt alpha-adrenergic vasoconstriction in the resting human forearm.

Angiotensin II enhances norepinephrine spillover during sympathetic activation in conscious rabbits.

PubMed

Noshiro, T; Shimizu, K; Way, D; Miura, Y; McGrath, B P

1994-05-01

To investigate the potential modulating influence of angiotensin II (ANG II) on sympathetic activity in response to changes in baroreflex activity, renal and total norepinephrine (NE) spillover rates were examined during sodium nitroprusside (SNP) and phenylephrine (PE) infusions in four groups of conscious rabbits: 1) saline (control); 2) subpressor ANG II (ANG II, 2 ng.kg-1.min-1); 3) enalaprilat (MK-422, 200 micrograms/kg and 3.3 micrograms.kg-1.min-1); and 4) MK plus ANG II (MK+ANG II). Upper plateaus of baroreflex-NE spillover curves for renal and total NE spillover were reduced in the MK group (25 and 81 ng/min) compared with control (38 and 125 ng/min) and MK+ANG II (37 and 155 ng/min). To investigate the interaction of ANG II and sympathetic activity during treadmill exercise, hindlimb NE spillover rate was examined in three groups of rabbits: 1) control, 2) MK, and 3) MK+ANG II. Exercise at 6 and 12 m/min produced similar effort-related hemodynamic responses in the three groups. At maximal exercise, hindlimb NE spillover was reduced in the MK group (29 +/- 3 ng/min) compared with control (62 +/- 17 ng/min, P < 0.05) and MK+ANG II group (51 +/- 10 ng/min). It is concluded that endogenous ANG II enhances sympathetic activity during pharmacological (baroreflex) and physiological stimulation.

Influence of physical preconditioning on the responsiveness of rat pulmonary artery after pulmonary ischemia/reperfusion.

PubMed

Delbin, Maria Andréia; Moraes, Camila; Camargo, Enilton; Mussi, Ricardo K; Antunes, Edson; de Nucci, Gilberto; Zanesco, Angelina

2007-07-01

The aim of this work was to evaluate the effect of physical preconditioning in the responsiveness of rat pulmonary rings submitted to lung ischemia/reperfusion (IR). Wistar rats were divided into three groups: Sedentary sham-operated (SD/SHAM); sedentary submitted to ischemia/reperfusion (SD/IR) and trained submitted to ischemia/reperfusion (TR/IR) animals. Exercise training consisted in sessions of 60 min/day running sessions, 5 days/week for 8 weeks. Left pulmonary IR was performed by occluding for 90 min and reperfusing for 120 min. After that, pulmonary arteries were isolated and concentration-response curves to acetylcholine (ACh), histamine (HIST), sodium nitroprusside (SNP), phenylephrine and U46619 were obtained. Neither potency (-log EC(50)) nor maximal responses (E(max)) were modified for ACh and HIST in all groups. On the other hand, the potency for SNP was significantly increased in TR/IR group (8.23+/-0.06) compared to SD/IR group (7.85+/-0.04). Contractile responses mediated by a-adrenergic receptor were markedly decreased in IR groups (SD/IR: 6.75+/-0.06 and TR/IR: 6.62+/-0.04) compared to SD/SHAM (7.33+/-0.05). No changes were seen for the U46619 in all groups. In conclusion, the present study shows that exercise training has no protective actions in the local blood vessel where the IR process takes place.

Acute toxicity of some synthetic cyanogens in rats: time-dependent cyanide generation and cytochrome oxidase inhibition in soft tissues after sub-lethal oral intoxication.

PubMed

Rao, Pooja; Singh, Poonam; Yadav, Shiv Kumar; Gujar, Niranjan L; Bhattacharya, Rahul

2013-09-01

Cyanogens include complex nitrile-containing compounds that can generate free cyanide of toxicological significance. Acute toxicity, time-dependent cyanide generation and cytochrome oxidase (CYTOX) inhibition in soft tissues, and urinary thiocyanate levels were measured after acute cyanogen intoxication in rats. Order of cyanogens in terms of LD₅₀ was: malononitrile (MCN)>propionitrile (PCN)≈sodium nitroprusside (SNP)>acrylonitrile (ACN)>succinonitrile (SCN)>acetonitrile (ATCN) for oral, and SNP>MCN>ACN>PCN>SCN>ATCN for intraperitoneal and subcutaneous routes. MCN was most toxic by oral (LD₅₀=66.4 mg/kg) and SNP by intraperitoneal (LD₅₀=16.7 mg/kg) and subcutaneous (LD₅₀=11.9 mg/kg) routes. Minimum survival time (25 min) was recorded after 4.0 LD₅₀ ATCN. Order of cyanogens (0.75 LD₅₀; oral) on the basis of maximum blood cyanide and time of peak cyanide generation were: ATCN>SNP>SCN>PCN>MCN>ACN, and MCN (30 min)

Mechanisms of the anti-hypertensive effect of Hibiscus sabdariffa L. calyces.

PubMed

Ajay, M; Chai, H J; Mustafa, A M; Gilani, A H; Mustafa, M R

2007-02-12

Previous studies have demonstrated the anti-hypertensive effects of Hibiscus sabdariffa L. (HS) in both humans and experimental animals. To explore the mechanisms of the anti-hypertensive effect of the HS, we examined the effects of a crude methanolic extract of the calyces of HS (HSE) on vascular reactivity in isolated aortas from spontaneously hypertensive rats. HSE relaxed, concentration-dependently, KCl (high K(+), 80 mM)- and phenylephrine (PE, 1 microM)-pre-contracted aortic rings, with a greater potency against the alpha(1)-adrenergic receptor agonist. The relaxant effect of HSE was partly dependent on the presence of a functional endothelium as the action was significantly reduced in endothelium-denuded aortic rings. Pretreatment with atropine (1 microM), L-NAME (10 microM) or methylene blue (10 microM), but not indomethacin (10 microM), significantly blocked the relaxant effects of HSE. Endothelium-dependent and -independent relaxations induced by acetylcholine and sodium nitroprusside, respectively, were significantly enhanced in aortic rings pretreated with HSE when compared to those observed in control aortic rings. The present results demonstrated that HSE has a vasodilator effect in the isolated aortic rings of hypertensive rats. These effects are probably mediated through the endothelium-derived nitric oxide-cGMP-relaxant pathway and inhibition of calcium (Ca(2+))-influx into vascular smooth muscle cells. The present data further supports previous in vivo findings and the traditional use of HS as an anti-hypertensive agent.

Inhibition of epithelial Na sup + transport by atriopeptin, protein kinase c, and pertussis toxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mohrmann, M.; Cantiello, H.F.; Ausiello, D.A.

1987-08-01

The authors have recently shown the selective inhibition of an amiloride-sensitive, conductive pathway for Na{sup +} by atrial natriuretic peptide and 8-bromoguanosine 3{prime},5{prime}-cyclic monophosphate (8-BrcGMP) in the renal epithelial cell line, LLC-PK{sub i}. Using {sup 22}Na{sup +} fluxes, they further investigated the modulation of Na{sup +} transport by atrial natriuretic peptide and by agents that increase cGMP production, activate protein kinase c, or modulate guanine nucleotide regulatory protein function. Sodium nitroprusside increases intracellular cGMP concentrations without affecting cAMP concentrations and completely inhibits amiloride-sensitive Na{sup +} uptake in a time- and concentration-dependent manner. Oleoyl 2-acetylglycerol and phorbol 12-myristate 13-acetate, activators ofmore » protein kinase c, inhibit Na{sup +} uptake by 93 {plus minus} 13 and 51 {plus minus} 10%, respectively. Prolonged incubation with phorbol ester results in the downregulation of protein kinase c activity and reduces the inhibitory effect of atrial natriuretic peptide, suggesting that the action of this peptide involves stimulation of protein kinase c. Pertussis toxin, which induces the ADP-ribosylation of a 41-kDa guanine nucleotide regulatory protein in LLC-PK{sub i} cells, inhibits {sup 22}Na{sup +} influx to the same extent as amiloride. Thus, increasing cGMP, activating protein kinase c, and ADP-ribosylating a guanine nucleotide regulatory protein all inhibit Na{sup +} uptake. These events may be sequentially involved in the action of atrial natriuretic peptide.« less

Nitric oxide-activated hydrogen sulfide is essential for cadmium stress response in bermudagrass (Cynodon dactylon (L). Pers.).

PubMed

Shi, Haitao; Ye, Tiantian; Chan, Zhulong

2014-01-01

Nitric oxide (NO) and hydrogen sulfide (H2S) are important gaseous molecules, serving as important secondary messengers in plant response to various biotic and abiotic stresses. However, the interaction between NO and H2S in plant stress response was largely unclear. In this study, endogenous NO and H2S were evidently induced by cadmium stress treatment in bermudagrass, and exogenous applications of NO donor (sodium nitroprusside, SNP) or H2S donor (sodium hydrosulfide, NaHS) conferred improved cadmium stress tolerance. Additionally, SNP and NaHS treatments alleviated cadmium stress-triggered plant growth inhibition, cell damage and reactive oxygen species (ROS) burst, partly via modulating enzymatic and non-enzymatic antioxidants. Moreover, SNP and NaHS treatments also induced the productions of both NO and H2S in the presence of Cd. Interestingly, combined treatments with inhibitors and scavengers of NO and H2S under cadmium stress condition showed that NO signal could be blocked by both NO and H2S inhibitors and scavengers, while H2S signal was specifically blocked by H2S inhibitors and scavengers, indicating that NO-activated H2S was essential for cadmium stress response. Taken together, we assigned the protective roles of endogenous and exogenous NO and H2S in bermudagrass response to cadmium stress, and speculated that NO-activated H2S might be essential for cadmium stress response in bermudagrass. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

In vivo imaging of reactive oxygen species in mouse brain by using [3H]Hydromethidine as a potential radical trapping radiotracer

PubMed Central

Abe, Kohji; Takai, Nozomi; Fukumoto, Kazumi; Imamoto, Natsumi; Tonomura, Misato; Ito, Miwa; Kanegawa, Naoki; Sakai, Katsunori; Morimoto, Kenji; Todoroki, Kenichiro; Inoue, Osamu

2014-01-01

To assess reactive oxygen species (ROS) production by detecting the fluorescent oxidation product, hydroethidine has been used extensively. The present study was undertaken to evaluate the potential of the hydroethidine derivative as a radiotracer to measure in vivo brain ROS production. [3H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([3H]Hydromethidine) was synthesized, and evaluated using in vitro radical-induced oxidization and in vivo brain ROS production model. In vitro studies have indicated that [3H]Hydromethidine is converted to oxidized products by a superoxide radical (O2•−) and a hydroxyl radical (OH•−) but not hydrogen peroxide (H2O2). In vivo whole-body distribution study showed that [3H]Hydromethidine rapidly penetrated the brain and then was washed out in normal mice. Microinjection of sodium nitroprusside (SNP) into the brain was performed to produce ROS such as OH•− via Fenton reaction. A significant accumulation of radioactivity immediately after [3H]Hydromethidine injection was seen in the side of the brain treated with SNP (5 and 20 nmol) compared with that in the contralateral side. These results indicated that [3H]Hydromethidine freely penetrated into the brain where it was rapidly converted to oxidized forms, which were trapped there in response to the production of ROS. Thus, [3H]Hydromethidine should be useful as a radical trapping radiotracer in the brain. PMID:25227606

Cloning and characterization of a heme oxygenase-2 gene from alfalfa (Medicago sativa L.).

PubMed

Fu, Guang-Qing; Jin, Qi-Jiang; Lin, Yu-Ting; Feng, Jian-Fei; Nie, Li; Shen, Wen-Biao; Zheng, Tian-Qing

2011-11-01

Heme oxygenase (HO, EC 1.14.99.3) catalyzes the oxidation of heme and performs vital roles in plant development and stress responses. Two HO isozymes exist in plants. Between these, HO-1 is an oxidative stress-response protein, and HO-2 usually exhibited constitutive expression. Although alfalfa HO-1 gene (MsHO1) has been investigated previously, HO2 is still poorly understood. In this study, we report the cloning and characterization of HO2 gene, MsHO2, from alfalfa (Medica sativa L.). The full-length cDNA of MsHO2 contains an ORF of 870 bp and encodes for 290 amino acid residues with a predicted molecular mass of 33.3 kDa. Similar to MsHO1, MsHO2 also appears to have an N-terminal transit peptide sequence for chloroplast import. Many conserved residues in plant HO were also conserved in MsHO2. However, unlike HO-1, the conserved histidine (His) required for heme-iron binding and HO activity was replaced by tyrosine (Tyr) in MsHO2. Further biochemical activity analysis of purified mature MsHO2 showed no HO activity, suggesting that MsHO2 may not be a true HO in nature. Semi-quantitative RT-PCR confirmed its maximum expression in the germinating seeds. Importantly, the expression levels of MsHO2 were up-regulated under sodium nitroprusside (SNP) and H(2)O(2) (especially) treatment, respectively.

How exogenous nitric oxide regulates nitrogen assimilation in wheat seedlings under different nitrogen sources and levels

PubMed Central

Balotf, Sadegh; Islam, Shahidul; Kavoosi, Gholamreza; Kholdebarin, Bahman; Juhasz, Angela

2018-01-01

Nitrogen (N) is one of the most important nutrients for plants and nitric oxide (NO) as a signaling plant growth regulator involved in nitrogen assimilation. Understanding the influence of exogenous NO on nitrogen metabolism at the gene expression and enzyme activity levels under different sources of nitrogen is vitally important for increasing nitrogen use efficiency (NUE). This study investigated the expression of key genes and enzymes in relation to nitrogen assimilation in two Australian wheat cultivars, a popular high NUE cv. Spitfire and a normal NUE cv. Westonia, under different combinations of nitrogen and sodium nitroprusside (SNP) as the NO donor. Application of NO increased the gene expressions and activities of nitrogen assimilation pathway enzymes in both cultivars at low levels of nitrogen. At high nitrogen supplies, the expressions and activities of N assimilation genes increased in response to exogenous NO only in cv. Spitfire but not in cv. Westonia. Exogenous NO caused an increase in leaf NO content at low N supplies in both cultivars, while under high nitrogen treatments, cv. Spitfire showed an increase under ammonium nitrate (NH4NO3) treatment but cv. Westonia was not affected. N assimilation gene expression and enzyme activity showed a clear relationship between exogenous NO, N concentration and N forms in primary plant nitrogen assimilation. Results reveal the possible role of NO and different nitrogen sources on nitrogen assimilation in Triticum aestivum plants. PMID:29320529

Virgin Coconut Oil Prevents Blood Pressure Elevation and Improves Endothelial Functions in Rats Fed with Repeatedly Heated Palm Oil

PubMed Central

Nurul-Iman, Badlishah Sham; Kamisah, Yusof; Jaarin, Kamsiah; Qodriyah, Hj Mohd Saad

2013-01-01

This study was performed to explore the effects of virgin coconut oil (VCO) in male rats that were fed with repeatedly heated palm oil on blood pressure, plasma nitric oxide level, and vascular reactivity. Thirty-two male Sprague-Dawley rats were divided into four groups: (i) control (basal diet), (ii) VCO (1.42 mL/kg, oral), (iii) five-times-heated palm oil (15%) (5HPO), and (iv) five-times-heated palm oil (15%) and VCO (1.42 mL/kg, oral) (5HPO + VCO). Blood pressure was significantly increased in the group that was given the 5HPO diet compared to the control group. Blood pressure in the 5HPO + VCO group was significantly lower than the 5HPO group. Plasma nitric oxide (NO) level in the 5HPO group was significantly lower compared to the control group, whereas in the 5HPO + VCO group, the plasma NO level was significantly higher compared to the 5HPO group. Aortic rings from the 5HPO group exhibited attenuated relaxation in response to acetylcholine and sodium nitroprusside as well as increased vasoconstriction to phenylephrine compared to the control group. Aortic rings from the 5HPO + VCO group showed only attenuated vasoconstriction to phenylephrine compared to the 5HPO group. In conclusion, VCO prevents blood pressure elevation and improves endothelial functions in rats fed with repeatedly heated palm oil. PMID:23861707

Virgin coconut oil prevents blood pressure elevation and improves endothelial functions in rats fed with repeatedly heated palm oil.

PubMed

Nurul-Iman, Badlishah Sham; Kamisah, Yusof; Jaarin, Kamsiah; Qodriyah, Hj Mohd Saad

2013-01-01

This study was performed to explore the effects of virgin coconut oil (VCO) in male rats that were fed with repeatedly heated palm oil on blood pressure, plasma nitric oxide level, and vascular reactivity. Thirty-two male Sprague-Dawley rats were divided into four groups: (i) control (basal diet), (ii) VCO (1.42 mL/kg, oral), (iii) five-times-heated palm oil (15%) (5HPO), and (iv) five-times-heated palm oil (15%) and VCO (1.42 mL/kg, oral) (5HPO + VCO). Blood pressure was significantly increased in the group that was given the 5HPO diet compared to the control group. Blood pressure in the 5HPO + VCO group was significantly lower than the 5HPO group. Plasma nitric oxide (NO) level in the 5HPO group was significantly lower compared to the control group, whereas in the 5HPO + VCO group, the plasma NO level was significantly higher compared to the 5HPO group. Aortic rings from the 5HPO group exhibited attenuated relaxation in response to acetylcholine and sodium nitroprusside as well as increased vasoconstriction to phenylephrine compared to the control group. Aortic rings from the 5HPO + VCO group showed only attenuated vasoconstriction to phenylephrine compared to the 5HPO group. In conclusion, VCO prevents blood pressure elevation and improves endothelial functions in rats fed with repeatedly heated palm oil.

The mechanisms of protection of antioxidants on Nostoc sphaeroides against UV-B radiation

NASA Astrophysics Data System (ADS)

Wang, G. H.

UV radiation is one of space harmful factor for earth organisms in space exploration In the present work we studied on the role of antioxidant system in Nostoc sphaeroides K u tz Cyanobacteria and the effects of exogenous antioxidant molecules on its photosynthetic rate under UV-B radiation It was found that UV-B radiation decreased the photosynthetic activity of cyanobacterium but promoted the activity of antioxidant system to protect photosystem II PSII and exogenous antioxidant sodium nitroprusside SNP N-acetylcysteine NAC had an obvious protection on PSII activity under UV-B radiation The activity of SOD Superoxide Dismutase EC 1 15 1 1 CAT Catalase EC 1 11 1 6 POD Peroxidase EC 1 11 1 7 and content of MDA and ASC were improved by 0 5mM and 1mM SNP but 0 1mM SNP decreased the activity of antioxide system Exogenous NAC addition decreased the activity of SOD POD CAT and the content MDA and ASC but exogenous NAC addition increased the content of GSH The results suggested that exogenous SNP and NAC may protect algae by different mechanisms in which SNP maybe play double roles as sources of reactive free radicals or ROS scavengers in formation of algae s protection of PSII under UV-B radiation while NAC does function as antioxidant reagent or precursor of glutathione which could protect PSII directly from UV-B radiation Keyword antioxidant system exogenous or endogenous antioxidant Nostoc sphaeroides photosynthesis UV-B radiation

The response of antioxidant systems in Nostoc sphaeroides against UV-B radiation and the protective effects of exogenous antioxidants

NASA Astrophysics Data System (ADS)

Wang, Gaohong; Hu, Chunxiang; Li, Dunhai; Zhang, Delu; Li, Xiaoyan; Chen, Kun; Liu, Yongding

UV radiation is one of many harmful factors found in space that are detrimental to organisms on earth in space exploration. In the present work, we examined the role of antioxidant system in Nostoc sphaeroides Kütz (Cyanobacterium) and the effects of exogenously applied antioxidant molecules on its photosynthetic rate under UV-B radiation. It was found that UV-B radiation promoted the activity of antioxidant system to protect photosystem II (PSII) and exogenously applied antioxidant: sodium nitroprusside (SNP) and N-acetylcysteine (NAC) had an obvious protection on PSII activity under UV-B radiation. The activity of superoxide dismutase (SOD, EC 1.15.1.1), catalase (CAT, EC 1.11.1.6), peroxidase (POD, EC 1.11.1.7) and content of MDA (malondialdehyde) and ASC (ascorbate) were improved by 0.5 mM and 1 mM SNP, but 0.1 mM SNP decreased the activity of antioxidant system. Addition of exogenous NAC decreased the activity of SOD, POD, CAT and the content MDA and ASC. In contrast, exogenously applied NAC increased GSH content. The results suggest that exogenous SNP and NAC may protect algae by different mechanisms: SNP may play double roles as both sources of reactive free radicals as well as ROS scavengers in mediating the protective role of PSII on algae under UV-B radiation. On the other hand, NAC functions as an antioxidant or precursor of glutathione, which could protect PSII directly from UV-B radiation.

Role of sex steroids in modulating tumor necrosis factor alpha induced changes in vascular function and blood pressure

PubMed Central

LaMarca, Babbette D.; Chandler, Derrick L.; Grubbs, Lee; Bain, Jennifer; McLemore, Gerald R.; Granger, Joey P.; Ryan, Michael J.

2007-01-01

Background We previously showed that infusion of TNF-α induces hypertension and vascular dysfunction in late pregnant but not virgin rats. In the present study we tested the hypothesis that levels of ovarian hormones to mimic pregnancy are required for TNF-α induced changes in vascular function and blood pressure in rats. Methods 21 day release pellets containing 17β-estradiol, progesterone, or both were implanted in ovariectomized (OVX) rats. Sham OVX rats were used as controls. 12 days after implantation, TNF-α or vehicle was infused via osmotic minipumps (days 12-17). On day 18, mean arterial pressure was measured and animals were sacrificed to assess vascular function. Results Average estrogen and progesterone levels across all groups were 106±6 pg/ml and 88±5 ng/ml. TNF-α was 41±7 pg/ml compared to OVX rats infused with vehicle (4±1 pg/ml). The results show that TNF-α did not cause elevated mean arterial pressure in OVX rats with increased estrogen, progesterone, both. Vascular responses to the endothelium dependent and independent agonists, acetylcholine and sodium nitroprusside, were also not changed. Phenylephrine induced contraction was moderately but significantly increased at the highest concentrations (10-4 M) only in TNF-α infused rats. Conclusion These data suggest that increased ovarian hormones to levels observed during pregnancy are not sufficient to promote TNF-α induced increases in blood pressure or vascular dysfunction. PMID:17954370

Baroreflex failure in a patient with central nervous system lesions involving the nucleus tractus solitarii

NASA Technical Reports Server (NTRS)

Biaggioni, I.; Whetsell, W. O.; Jobe, J.; Nadeau, J. H.

1994-01-01

Animal studies have shown the importance of the nucleus tractus solitarii, a collection of neurons in the brain stem, in the acute regulation of blood pressure. Impulses arising from the carotid and aortic baroreceptors converge in this center, where the first synapse of the baroreflex is located. Stimulation of the nucleus tractus solitarii provides an inhibitory signal to other brain stem structures, particularly the rostral ventrolateral medulla, resulting in a reduction in sympathetic outflow and a decrease in blood pressure. Conversely, experimental lesions of the nucleus tractus solitarii lead to loss of baroreflex control of blood pressure, sympathetic activation, and severe hypertension in animals. In humans, baroreflex failure due to deafferentation of baroreceptors has been previously reported and is characterized by episodes of severe hypertension and tachycardia. We present a patient with an undetermined process of the central nervous system characterized pathologically by ubiquitous infarctions that were particularly prominent in the nucleus tractus solitarii bilaterally but spared the rostral ventrolateral medulla. Absence of a functioning baroreflex was evidenced by the lack of reflex tachycardia to the hypotensive effects of sodium nitroprusside, exaggerated pressor responses to handgrip and cold pressor test, and exaggerated depressor responses to meals and centrally acting alpha 2-agonists. This clinicopathological correlate suggests that the patient's baroreflex failure can be explained by the unique combination of the destruction of sympathetic inhibitory centers (ie, the nucleus tractus solitarii) and preservation of centers that exert a positive modulation on sympathetic tone (ie, the rostral ventrolateral medulla).

Chitosan-induced immunity in Camellia sinensis (L.) O. Kuntze against blister blight disease is mediated by nitric-oxide.

PubMed

Chandra, Swarnendu; Chakraborty, Nilanjan; Panda, Koustubh; Acharya, Krishnendu

2017-06-01

Blister blight disease, caused by an obligate biotrophic fungal pathogen, Exobasidium vexans Massee is posing a serious threat for tea cultivation in Asia. As the use of chemical pesticides on tea leaves substantially increases the toxic risks of tea consumption, serious attempts are being made to control such pathogens by boosting the intrinsic natural defense responses against invading pathogens in tea plants. In this study, the nature and durability of resistance offered by chitosan and the possible mechanism of chitosan-induced defense induction in Camellia sinensis (L.) O. Kuntze plants against blister blight disease were investigated. Foliar application of 0.01% chitosan solution at 15 days interval not only reduced the blister blight incidence for two seasons, but also maintained the induced expressions of different defense related enzymes and total phenol content compared to the control. Defense responses induced by chitosan were found to be down regulated under nitric oxide (NO) deficient conditions in vivo, indicating that the observed chitosan-induced resistance is probably activated via NO signaling. Such role of NO in host defense response was further established by application of the NO donor, sodium nitroprusside (SNP), which produced similar defense responses accomplished through chitosan treatment. Taken together, our results suggest that increased production of NO in chitosan-treated tea plants may play a critical role in triggering the innate defense responses effective against plant pathogens, including that causing the blister blight disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Pulmonary Nanoparticle Exposure Disrupts Systemic Microvascular Nitric Oxide Signaling

PubMed Central

Nurkiewicz, Timothy R.; Porter, Dale W.; Hubbs, Ann F.; Stone, Samuel; Chen, Bean T.; Frazer, David G.; Boegehold, Matthew A.; Castranova, Vincent

2009-01-01

We have shown that pulmonary nanoparticle exposure impairs endothelium dependent dilation in systemic arterioles. However, the mechanism(s) through which this effect occurs is/are unclear. The purpose of this study was to identify alterations in the production of reactive species and endogenous nitric oxide (NO) after nanoparticle exposure, and determine the relative contribution of hemoproteins and oxidative enzymes in this process. Sprague-Dawley rats were exposed to fine TiO2 (primary particle diameter ∼1 μm) and TiO2 nanoparticles (primary particle diameter ∼21 nm) via aerosol inhalation at depositions of 4–90 μg per rat. As in previous intravital experiments in the spinotrapezius muscle, dose-dependent arteriolar dilations were produced by intraluminal infusions of the calcium ionophore A23187. Nanoparticle exposure robustly attenuated these endothelium-dependent responses. However, this attenuation was not due to altered microvascular smooth muscle NO sensitivity because nanoparticle exposure did not alter arteriolar dilations in response to local sodium nitroprusside iontophoresis. Nanoparticle exposure significantly increased microvascular oxidative stress by ∼60%, and also elevated nitrosative stress fourfold. These reactive stresses coincided with a decreased NO production in a particle deposition dose-dependent manner. Radical scavenging, or inhibition of either myeloperoxidase or nicotinamide adenine dinucleotide phosphate oxidase (reduced) oxidase partially restored NO production as well as normal microvascular function. These results indicate that in conjunction with microvascular dysfunction, nanoparticle exposure also decreases NO bioavailability through at least two functionally distinct mechanisms that may mutually increase local reactive species. PMID:19270016

Fabrication and characterization of sol-gel based nanoparticles for drug delivery

NASA Astrophysics Data System (ADS)

Yadav, Reeta

Nanogels are cross linked polymeric sol-gel based nanoparticles that offer an interior network for incorporation and protection of biomolecules, exhibiting unique advantages for polymer based delivery systems. We have successfully synthesized stable sol-gel nanoparticles by means of [a] silicification reactions using cationic peptides like polylysine as gelating agents, and [b] lyophilization of sol-gels. Macromolecules such as Hemoglobin and Glucose Oxidase and small molecules such as Sodium Nitroprusside (SNP) and antibiotics were encapsulated within the nanogels. We have used transmission electron microscopy, dynamic light scattering, zeta potential analysis, and spectroscopy to perform a physicochemical characterization of the nanogels resulting from the two approaches. Our studies have indicated that the nanogel encapsulated proteins and small molecules remain intact, stable and functional. A Hydrogen Peroxide (H2O2) and Nitric Oxide (NO) generating drug carrier was synthesized using these nanogels and the effect of generation of H2O2 from Glucose Oxidase encapsulated nanogels and NO from SNP encapsulated nanogels was tested on E.coli. The results show that the nanoparticles exert antimicrobial activity against E.Coli, in addition NO generating nanogels potentiated H2O2 generating nanogels induced killing. These data suggest that these NO and H2O2 releasing nanogels have the potential to serve as a novel class of antimicrobials for the treatment of multidrug resistant bacteria. The unique properties of these protein/drug incorporated nanogels raise the prospect of fine tailoring to specific applications such as drug delivery and bio imaging.

High-dose atorvastatin is associated with lower IGF-1 levels in patients with type 1 diabetes.

PubMed

Bergen, Karin; Brismar, Kerstin; Tehrani, Sara

2016-08-01

Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 (IGFBP-1) play an important role in vascular health. Many patients with type 1 diabetes are medicated with HMG-CoA reductase inhibitors, statins, in order to prevent vascular complications. Yet little is known about the effect of statins on the IGF-1/IGFBP-1 axis in these patients. The aim of this study was to evaluate the effect of atorvastatin treatment on IGF-1 and IGFBP-1 with regards to microvascular function. Twenty patients with type 1 diabetes received either placebo or 80mg atorvastatin for two months in a double-blinded cross-over study. IGF-1 and IGFBP-1 levels were assessed before and after each treatment period. Skin microcirculation was studied using Doppler perfusion imaging during iontophoresis of acetylcholine and sodium nitroprusside to assess endothelium-dependent and endothelium-independent microvascular reactivity, respectively. Treatment with high-dose atorvastatin was associated with a significant decrease in IGF-1 levels compared to placebo (p<0.05, ANOVA repeated measures), whereas no effect was seen on IGFBP-1 or the IGF-1/IGFBP-1 ratio. These variables did not correlate with measurements of skin microvascular reactivity. The study found that treatment with high-dose atorvastatin was associated with reduced IGF-1 levels, which may indicate a potential negative effect on microvascular function and long-term risk of microangiopathy development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Detection of S-Nitrosothiol and Nitrosylated Proteins in Arachis hypogaea Functional Nodule: Response of the Nitrogen Fixing Symbiont

PubMed Central

Maiti, Debasis; Sarkar, Tuhin Subhra; Ghosh, Sanjay

2012-01-01

To detect the presence of NO, ROS and RNS in nodules of crack entry legumes, we used Arachis hypogaea functional nodule. The response of two cognate partner rhizobia was compared towards NO and GSNO using S. meliloti and Bradyrhizobium sp NC921001. ROS, NO, nitrosothiol and bacteroids were detected by fluorescence microscopy. Redox enzymes and thiol pools were detected biochemically. Nitrosothiols were found to be present but ROS and NO were absent in A. hypogaea nodule. A number of S-nitrosylated proteins were also detected. The total thiol pool and most of the redox enzymes were low in nodule cytosolic extract but these were found to be high in the partner microorganisms indicating partner rhizobia could protect the nodule environment against the nitrosothiols. Both S. meliloti and Bradyrhizobium sp NC921001 were found to contain GSNO reductase. Interestingly, there was a marked difference in growth pattern between S. meliloti and Bradyrhizobium sp in presence of sodium nitroprusside (SNP) and S-nitrosoglutathione (GSNO). Bradyrhizobium sp was found to be much more tolerant to NO donor compounds than the S. meliloti. In contrast, S. meliloti showed resistance to GSNO but was sensitive to SNP. Together our data indicate that nodule environment of crack entry legumes is different than the nodules of infection mode entry in terms of NO, ROS and RNS. Based on our biochemical characterization, we propose that exchange of redox molecules and reactive chemical species is possible between the bacteroid and nodule compartment. PMID:23029073

Differential sensitivities of pulmonary and coronary arteries to hemoglobin-based oxygen carriers and nitrovasodilators: study in a bovine ex vivo model of vascular strips.

PubMed

Fonseca, Vera; Avizinis, Jessica; Moon-Massat, Paula; Freilich, Daniel; Kim, Hae Won; Hai, Chi-Ming

2010-01-01

Vasoconstriction is a major adverse effect of first and second generation hemoglobin-based oxygen carriers (HBOCs) that hinders their development as blood substitute. However, intravenous infusion of HBOC-201 (second generation) to patients induces significant pulmonary hypertension without significant coronary vasoconstriction. We compared contractile responses of isolated bovine pulmonary and coronary arterial strips to HBOC-201 and HBOC-205LL.LT.MW600 (third generation), polymerized bovine hemoglobins of different molecular weight, and their attenuation by nitroglycerin, sodium nitroprusside (SNP), and sodium nitrite. Pulmonary arteries developed negligible basal tone, but exhibited HBOC-dependent amplification of phenylephrine-induced contractions. In contrast, coronary arteries developed significant basal tone, and exhibited HBOC-dependent constant force increment to serotonin-induced contractions. Therefore, relative to basal tone, HBOC-induced contractions were greater in pulmonary than coronary arteries. Furthermore, HBOC-205LL.LT.MW600 appeared to be less vasoactive than HBOC-201. Unexpectedly, pulmonary and coronary arteries exhibited differential sensitivities to nitrovasodilators in parallel with their differential sensitivities to HBOC. However, SNP and sodium nitrite induced significant methemoglobin formation from HBOC, whereas nitroglycerin did not. These results suggest that phenotypic differences between pulmonary and coronary vascular smooth muscle cells could explain the differential hypertensive effects of HBOC on pulmonary and coronary circulation in patients. Among the three nitrovasodilators investigated, nitroglycerin appears to be the most promising candidate for attenuating HBOC-induced pulmonary hypertension in older HBOCs.

Tumor necrosis factor-alpha inhibits insulin's stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans.

PubMed

Rask-Madsen, Christian; Domínguez, Helena; Ihlemann, Nikolaj; Hermann, Thomas; Køber, Lars; Torp-Pedersen, Christian

2003-10-14

Inflammatory mechanisms could be involved in the pathogenesis of both insulin resistance and atherosclerosis. Therefore, we aimed at examining whether the proinflammatory cytokine tumor necrosis factor (TNF)-alpha inhibits insulin-stimulated glucose uptake and insulin-stimulated endothelial function in humans. Healthy, lean male volunteers were studied. On each study day, 3 acetylcholine (ACh) or sodium nitroprusside (SNP) dose-response studies were performed by infusion into the brachial artery. Before and during the last 2 dose-response studies, insulin and/or TNF-alpha were coinfused. During infusion of insulin alone for 20 minutes, forearm glucose uptake increased by 220+/-44%. This increase was completely inhibited during coinfusion of TNF-alpha (started 10 min before insulin) with a more pronounced inhibition of glucose extraction than of blood flow. Furthermore, TNF-alpha inhibited the ACh forearm blood flow response (P<0.001), and this inhibition was larger during insulin infusion (P=0.01) but not further increased by NG-monomethyl-L-arginine acetate (P=0.2). Insulin potentiated the SNP response less than the ACh response and the effect of TNF-alpha was smaller (P<0.001); TNF-alpha had no effect on the SNP response without insulin infusion. Thus, TNF-alpha inhibition of the combined response to insulin and ACh was likely mediated through inhibition of NO production. These results support the concept that TNF-alpha could play a role in the development of insulin resistance in humans, both in muscle and in vascular tissue.

Oral trehalose supplementation improves resistance artery endothelial function in healthy middle-aged and older adults.

PubMed

Kaplon, Rachelle E; Hill, Sierra D; Bispham, Nina Z; Santos-Parker, Jessica R; Nowlan, Molly J; Snyder, Laura L; Chonchol, Michel; LaRocca, Thomas J; McQueen, Matthew B; Seals, Douglas R

2016-06-01

We hypothesized that supplementation with trehalose, a disaccharide that reverses arterial aging in mice, would improve vascular function in middle-aged and older (MA/O) men and women. Thirty-two healthy adults aged 50-77 years consumed 100 g/day of trehalose (n=15) or maltose (n=17, isocaloric control) for 12 weeks (randomized, double-blind). In subjects with Δbody mass less than 2.3kg (5 lb.), resistance artery endothelial function, assessed by forearm blood flow to brachial artery infusion of acetylcholine (FBFACh), increased ~30% with trehalose (13.3±1.0 vs. 10.5±1.1 AUC, P=0.02), but not maltose (P=0.40). This improvement in FBFACh was abolished when endothelial nitric oxide (NO) production was inhibited. Endothelium-independent dilation, assessed by FBF to sodium nitroprusside (FBFSNP), also increased ~30% with trehalose (155±13 vs. 116±12 AUC, P=0.03) but not maltose (P=0.92). Changes in FBFACh and FBFSNP with trehalose were not significant when subjects with Δbody mass ≥ 2.3kg were included. Trehalose supplementation had no effect on conduit artery endothelial function, large elastic artery stiffness or circulating markers of oxidative stress or inflammation (all P>0.1) independent of changes in body weight. Our findings demonstrate that oral trehalose improves resistance artery (microvascular) function, a major risk factor for cardiovascular diseases, in MA/O adults, possibly through increasing NO bioavailability and smooth muscle sensitivity to NO.

Oral trehalose supplementation improves resistance artery endothelial function in healthy middle-aged and older adults

PubMed Central

Kaplon, Rachelle E.; Hill, Sierra D.; Bispham, Nina Z.; Santos-Parker, Jessica R.; Nowlan, Molly J.; Snyder, Laura L.; Chonchol, Michel; LaRocca, Thomas J.; McQueen, Matthew B.; Seals, Douglas R.

2016-01-01

We hypothesized that supplementation with trehalose, a disaccharide that reverses arterial aging in mice, would improve vascular function in middle-aged and older (MA/O) men and women. Thirty-two healthy adults aged 50-77 years consumed 100 g/day of trehalose (n=15) or maltose (n=17, isocaloric control) for 12 weeks (randomized, double-blind). In subjects with Δbody mass<2.3kg (5 lb.), resistance artery endothelial function, assessed by forearm blood flow to brachial artery infusion of acetylcholine (FBFACh), increased ∼30% with trehalose (13.3±1.0 vs. 10.5±1.1 AUC, P=0.02), but not maltose (P=0.40). This improvement in FBFACh was abolished when endothelial nitric oxide (NO) production was inhibited. Endothelium-independent dilation, assessed by FBF to sodium nitroprusside (FBFSNP), also increased ∼30% with trehalose (155±13 vs. 116±12 AUC, P=0.03) but not maltose (P=0.92). Changes in FBFACh and FBFSNP with trehalose were not significant when subjects with Δbody mass≥2.3kg were included. Trehalose supplementation had no effect on conduit artery endothelial function, large elastic artery stiffness or circulating markers of oxidative stress or inflammation (all P>0.1) independent of changes in body weight. Our findings demonstrate that oral trehalose improves resistance artery (microvascular) function, a major risk factor for cardiovascular diseases, in MA/O adults, possibly through increasing NO bioavailability and smooth muscle sensitivity to NO. PMID:27208415

Real-time measurements of endogenous CO production from vascular cells using an ultrasensitive laser sensor.

PubMed

Morimoto, Y; Durante, W; Lancaster, D G; Klattenhoff, J; Tittel, F K

2001-01-01

Carbon monoxide (CO) has been implicated as a biological messenger molecule analogous to nitric oxide. A compact gas sensor based on a midinfrared laser absorption spectroscopy was developed for direct and real-time measurement of trace levels (in approximate pmol) of CO release by vascular cells. The midinfrared light is generated by difference frequency mixing of two nearinfrared lasers in a nonlinear optical crystal. A strong infrared absorption line of CO (4.61 microm) is chosen for convenient CO detection without interference from other gas species. The generation of CO from cultured vascular smooth muscle cells was detected every 20 s without any chemical modification to the CO. The sensitivity of the sensor reached 6.9 pmol CO. CO synthesis was measured from untreated control cells (0.25 nmol per 10(7) cells/h), sodium nitroprusside-treated cells (0.29 nmol per 10(7) cells/h), and hemin-treated cells (0.49 nmol per 10(7) cells/h). The sensor also detected decreases in CO production after the addition of the heme oxygenase (HO) inhibitor tin protoporphyrin-IX (from 0.49 to 0.02 nmol per 10(7) cells/h) and increases after the administration of the HO substrate hemin (from 0.27 to 0.64 nmol per 10(7) cells/h). These results demonstrate that midinfrared laser absorption spectroscopy is a useful technique for the noninvasive and real-time detection of trace levels of CO from biological tissues.

Cardiovascular responses to microinjection of L-glutamate into the NTS in AV3V-lesioned rats.

PubMed

Vieira, Alexandre Antonio; Colombari, Eduardo; De Luca, Laurival A; de Almeida Colombari, Débora Simões; Menani, José V

2004-10-29

The excitatory amino acid L-glutamate injected into the nucleus of the solitary tract (NTS) in unanesthetized rats similar to peripheral chemoreceptor activation increases mean arterial pressure (MAP) and reduces heart rate. In this study, we investigated the effects of acute (1 day) and chronic (15 days) electrolytic lesions of the preoptic-periventricular tissue surrounding the anteroventral third ventricle (AV3V region) on the pressor and bradycardic responses induced by injections of L-glutamate into the NTS or peripheral chemoreceptor activation in unanesthetized rats. Male Holtzman rats with sham or electrolytic AV3V lesions and a stainless steel cannula implanted into the NTS were used. Differently from the pressor responses (28+/-3 mm Hg) produced by injections into the NTS of sham-lesioned rats, L-glutamate (5 nmol/100 nl) injected into the NTS reduced MAP (-26+/-8 mm Hg) or produced no effect (2+/-7 mm Hg) in acute and chronic AV3V-lesioned rats, respectively. The bradycardia to l-glutamate into the NTS and the cardiovascular responses to chemoreflex activation with intravenous potassium cyanide or to baroreflex activation with intravenous phenylephrine or sodium nitroprusside were not modified by AV3V lesions. The results show that the integrity of the AV3V region is essential for the pressor responses to L-glutamate into the NTS but not for the pressor responses to chemoreflex activation, suggesting dissociation between the central mechanisms involved in these responses.

Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle.

PubMed

Valenti, Vitor E; de Abreu, Luiz Carlos; Sato, Monica A; Ferreira, Celso; Adami, Fernando; Fonseca, Fernando L A; Xavier, Valdelias; Godoy, Moacir; Monteiro, Carlos B; Vanderlei, Luiz Carlos M; Saldiva, Paulo H N

2012-03-30

Cigarette exposure increases brain oxidative stress. The literature showed that increased brain oxidative stress affects cardiovascular regulation. However, no previous study investigated the involvement of brain oxidative stress in animals exposed to cigarette and its relationship with cardiovascular regulation. We aimed to evaluate the effects of central catalase inhibition on baroreflex and cardiovascular responses in rats exposed to sidestream cigarette smoke (SSCS). We evaluated males Wistar rats (320-370 g), which were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). Femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. Rats were exposed to SSCS during three weeks, 180 minutes, 5 days/week (CO: 100-300 ppm). Baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 μg/kg, bolus) to induce bradycardic reflex and a depressor dose of sodium nitroprusside (SNP, 50 μg/kg, bolus) to induce tachycardic reflex. Cardiovascular responses were evaluated before, 5, 15, 30 and 60 minutes after 3-amino-1,2,4-triazole (ATZ, catalase inhibitor, 0.001 g/100 μL) injection into the 4th V. Central catalase inhibition increased basal HR in the control group during the first 5 minutes. SSCS exposure increased basal HR and attenuated bradycardic peak during the first 15 minutes. We suggest that SSCS exposure affects cardiovascular regulation through its influence on catalase activity.

Genome-Scale Transcriptome Analysis in Response to Nitric Oxide in Birch Cells: Implications of the Triterpene Biosynthetic Pathway

PubMed Central

Zeng, Fansuo; Sun, Fengkun; Li, Leilei; Liu, Kun; Zhan, Yaguang

2014-01-01

Evidence supporting nitric oxide (NO) as a mediator of plant biochemistry continues to grow, but its functions at the molecular level remains poorly understood and, in some cases, controversial. To study the role of NO at the transcriptional level in Betula platyphylla cells, we conducted a genome-scale transcriptome analysis of these cells. The transcriptome of untreated birch cells and those treated by sodium nitroprusside (SNP) were analyzed using the Solexa sequencing. Data were collected by sequencing cDNA libraries of birch cells, which had a long period to adapt to the suspension culture conditions before SNP-treated cells and untreated cells were sampled. Among the 34,100 UniGenes detected, BLASTX search revealed that 20,631 genes showed significant (E-values≤10−5) sequence similarity with proteins from the NR-database. Numerous expressed sequence tags (i.e., 1374) were identified as differentially expressed between the 12 h SNP-treated cells and control cells samples: 403 up-regulated and 971 down-regulated. From this, we specifically examined a core set of NO-related transcripts. The altered expression levels of several transcripts, as determined by transcriptome analysis, was confirmed by qRT-PCR. The results of transcriptome analysis, gene expression quantification, the content of triterpenoid and activities of defensive enzymes elucidated NO has a significant effect on many processes including triterpenoid production, carbohydrate metabolism and cell wall biosynthesis. PMID:25551661

Real-time measurements of endogenous CO production from vascular cells using an ultrasensitive laser sensor

NASA Technical Reports Server (NTRS)

Morimoto, Y.; Durante, W.; Lancaster, D. G.; Klattenhoff, J.; Tittel, F. K.

2001-01-01

Carbon monoxide (CO) has been implicated as a biological messenger molecule analogous to nitric oxide. A compact gas sensor based on a midinfrared laser absorption spectroscopy was developed for direct and real-time measurement of trace levels (in approximate pmol) of CO release by vascular cells. The midinfrared light is generated by difference frequency mixing of two nearinfrared lasers in a nonlinear optical crystal. A strong infrared absorption line of CO (4.61 microm) is chosen for convenient CO detection without interference from other gas species. The generation of CO from cultured vascular smooth muscle cells was detected every 20 s without any chemical modification to the CO. The sensitivity of the sensor reached 6.9 pmol CO. CO synthesis was measured from untreated control cells (0.25 nmol per 10(7) cells/h), sodium nitroprusside-treated cells (0.29 nmol per 10(7) cells/h), and hemin-treated cells (0.49 nmol per 10(7) cells/h). The sensor also detected decreases in CO production after the addition of the heme oxygenase (HO) inhibitor tin protoporphyrin-IX (from 0.49 to 0.02 nmol per 10(7) cells/h) and increases after the administration of the HO substrate hemin (from 0.27 to 0.64 nmol per 10(7) cells/h). These results demonstrate that midinfrared laser absorption spectroscopy is a useful technique for the noninvasive and real-time detection of trace levels of CO from biological tissues.

Changes in cholinergic and nitrergic systems of defunctionalized colons after colostomy in rabbits.

PubMed

Moralıoğlu, Serdar; Vural, İsmail Mert; Özen, İbrahim Onur; Öztürk, Gökçe; Sarıoğlu, Yusuf; Başaklar, Abdullah Can

2017-01-01

This study was designed to assess smooth muscle function and motility in defunctionalized colonic segments and subsequent changes in pathways responsible for gastrointestinal motility. Two-month-old New Zealand rabbits were randomly allocated into control and study groups. Sigmoid colostomies were performed in the study group. After a 2-month waiting period, colonic segments were harvested in both groups. For the in vitro experiment, the isolated circular muscle strips which were prepared from the harvested distal colon were used. First, contraction responses were detected using KCl and carbachol; relaxation responses were detected using papaverine, sodium nitroprusside, sildenafil, and l-arginine. The neurologic responses of muscle strips to electrical field stimulation (EFS) were evaluated in an environment with guanethidine and indomethacin. EFS studies were then repeated with atropine, Nω-nitro-l-arginine methyl ester, atropine, and Nω-nitro-l-arginine methyl ester-added environments. Although macroscopic atrophy had developed in the distal colonic segment of the colostomy, the contraction and relaxation capacity of the smooth muscle did not change. EFS-induced nitrergic-peptidergic, cholinergic-peptidergic, and noncholinergic nonnitrergic responses significantly decreased at all frequencies (0.5-32 Hz) in the study group compared with those in the control group (P < 0.05). Although the contraction capacity of the smooth muscle was not affected, the motility of the distal colon deteriorated owing to the defective secretion of presynaptic neurotransmitters such as acetylcholine, nitric oxide, and neuropeptides. Copyright © 2016 Elsevier Inc. All rights reserved.

CKA2 functions in H2O2-induced apoptosis and high-temperature stress tolerance by regulating NO accumulation in yeast.

PubMed

Liu, Wen-Cheng; Yuan, Hong-Mei; Li, Yun-Hui; Lu, Ying-Tang

2015-09-01

Nitric oxide (NO) plays key roles in yeast responses to various environmental factors, such as H2O2 and high temperature. However, the gene encoding NO synthase (NOS) in yeast has not yet been identified, and the mechanism underlying the regulation of NOS-like activity is poorly understood. Here, we report on the involvement of CKA2 in H2O2-induced yeast apoptosis and yeast high-temperature stress tolerance. Our results showed that although Δcka2 mutant had reduced NO accumulation with decreased apoptosis after H2O2 exposure, treatment with a NO donor, sodium nitroprusside, resulted in similar survival rate of Δcka2 mutant compared to that of wild-type yeast when subjected to H2O2 stress. This finding occurred because H2O2-enhanced NOS-like activity in wild-type yeast was significantly repressed in Δcka2. Our additional experiments indicated that both high-temperature-enhanced NO accumulation and NOS-like activity were also suppressed in Δcka2, leading to the hypersensitivity of the mutant to high temperature in terms of changes in survival rate. Thus, our results showed that CKA2 functioned in H2O2-induced apoptosis and high-temperature stress tolerance by regulating NOS-like-dependent NO accumulation in yeast. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Tissue viability imaging: microvascular response to vasoactive drugs induced by iontophoresis.

PubMed

Henricson, Joakim; Nilsson, Anders; Tesselaar, Erik; Nilsson, Gert; Sjöberg, Folke

2009-09-01

When one is studying the physiology of the cutaneous microcirculation there is a need for relevant non-invasive and versatile techniques. In this study we used a new optical device, the tissue viability imager (TiVi), to map changes in cutaneous microvascular concentrations of red blood cells during iontophoresis of vasoactive substances (noradrenaline (NA) and phenylephrine (Phe) for vasoconstriction and acetylcholine (ACh) and sodium nitroprusside (SNP) for vasodilatation). We aimed to present data both individually and pooled, using a four-variable logistic dose response model that is commonly used in similar in vitro vascular studies. The accuracy of the TiVi was also investigated by calculating the coefficient of variation and comparing it with similar tests previously done using laser Doppler imaging. Tests were also performed using the TiVi and LDPI simultaneously to further compare the two methods. Results showed that the TiVi is capable of quantifying vascular responses to iontophorised noradrenaline and phenylephrine without the need to increase background flow first. Fitting the TiVi data to the dose response model resulted in ED(50)-values with narrow confidence intervals and acceptable r(2) values. Mean ED(50)-values for the TiVi did not differ significantly from similar values obtained using laser Doppler. Results further seem to suggest that when the blood perfusion increases during vasodilatation in skin the initial phase relies mainly on an increase in red blood cell concentration whereas the further perfusion increase is due to an increase in red blood cell velocity.

Identification of the Muscarinic Acetylcholine Receptor Subtype Mediating Cholinergic Vasodilation in Murine Retinal Arterioles

PubMed Central

Sniatecki, Jan J.; Goloborodko, Evgeny; Steege, Andreas; Zavaritskaya, Olga; Vetter, Jan M.; Grus, Franz H.; Patzak, Andreas; Wess, Jürgen; Pfeiffer, Norbert

2011-01-01

Purpose. To identify the muscarinic acetylcholine receptor subtype that mediates cholinergic vasodilation in murine retinal arterioles. Methods. Muscarinic receptor gene expression was determined in murine retinal arterioles using real-time PCR. To assess the functional relevance of muscarinic receptors for mediating vascular responses, retinal vascular preparations from muscarinic receptor–deficient mice were studied in vitro. Changes in luminal arteriole diameter in response to muscarinic and nonmuscarinic vasoactive substances were measured by video microscopy. Results. Only mRNA for the M3 receptor was detected in retinal arterioles. Thus, M3 receptor–deficient mice (M3R−/−) and respective wild-type controls were used for functional studies. Acetylcholine concentration-dependently dilated retinal arterioles from wild-type mice. In contrast, vasodilation to acetylcholine was almost completely abolished in retinal arterioles from M3R−/− mice, whereas responses to the nitric oxide (NO) donor nitroprusside were retained. Carbachol, an acetylcholinesterase-resistant analog of acetylcholine, also evoked dilation in retinal arterioles from wild-type, but not from M3R−/−, mice. Vasodilation responses from wild-type mice to acetylcholine were negligible after incubation with the non–subtype-selective muscarinic receptor blocker atropine or the NO synthase inhibitor Nω-nitro-l-arginine methyl ester, and were even reversed to contraction after endothelial damage with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. Conclusions. These findings provide evidence that endothelial M3 receptors mediate cholinergic vasodilation in murine retinal arterioles via activation of NO synthase. PMID:21873683

How exogenous nitric oxide regulates nitrogen assimilation in wheat seedlings under different nitrogen sources and levels.

PubMed

Balotf, Sadegh; Islam, Shahidul; Kavoosi, Gholamreza; Kholdebarin, Bahman; Juhasz, Angela; Ma, Wujun

2018-01-01

Nitrogen (N) is one of the most important nutrients for plants and nitric oxide (NO) as a signaling plant growth regulator involved in nitrogen assimilation. Understanding the influence of exogenous NO on nitrogen metabolism at the gene expression and enzyme activity levels under different sources of nitrogen is vitally important for increasing nitrogen use efficiency (NUE). This study investigated the expression of key genes and enzymes in relation to nitrogen assimilation in two Australian wheat cultivars, a popular high NUE cv. Spitfire and a normal NUE cv. Westonia, under different combinations of nitrogen and sodium nitroprusside (SNP) as the NO donor. Application of NO increased the gene expressions and activities of nitrogen assimilation pathway enzymes in both cultivars at low levels of nitrogen. At high nitrogen supplies, the expressions and activities of N assimilation genes increased in response to exogenous NO only in cv. Spitfire but not in cv. Westonia. Exogenous NO caused an increase in leaf NO content at low N supplies in both cultivars, while under high nitrogen treatments, cv. Spitfire showed an increase under ammonium nitrate (NH4NO3) treatment but cv. Westonia was not affected. N assimilation gene expression and enzyme activity showed a clear relationship between exogenous NO, N concentration and N forms in primary plant nitrogen assimilation. Results reveal the possible role of NO and different nitrogen sources on nitrogen assimilation in Triticum aestivum plants.

Hydrogen sulfide enhances salt tolerance through nitric oxide-mediated maintenance of ion homeostasis in barley seedling roots

PubMed Central

Chen, Juan; Wang, Wen-Hua; Wu, Fei-Hua; He, En-Ming; Liu, Xiang; Shangguan, Zhou-Ping; Zheng, Hai-Lei

2015-01-01

Hydrogen sulfide (H2S) and nitric oxide (NO) are emerging as messenger molecules involved in the modulation of plant physiological processes. Here, we investigated a signalling network involving H2S and NO in salt tolerance pathway of barley. NaHS, a donor of H2S, at a low concentration of either 50 or 100 μM, had significant rescue effects on the 150 mM NaCl-induced inhibition of plant growth and modulated the K+/Na+ balance by decreasing the net K+ efflux and increasing the gene expression of an inward-rectifying potassium channel (HvAKT1) and a high-affinity K+ uptake system (HvHAK4). H2S and NO maintained the lower Na+ content in the cytoplast by increasing the amount of PM H+-ATPase, the transcriptional levels of PM H+-ATPase (HvHA1) and Na+/H+ antiporter (HvSOS1). H2S and NO modulated Na+ compartmentation into the vacuoles with up-regulation of the transcriptional levels of vacuolar Na+/H+ antiporter (HvVNHX2) and H+-ATPase subunit β (HvVHA-β) and increased in the protein expression of vacuolar Na+/H+ antiporter (NHE1). H2S mimicked the effect of sodium nitroprusside (SNP) by increasing NO production, whereas the function was quenched with the addition of NO scavenger. These results indicated that H2S increased salt tolerance by maintaining ion homeostasis, which were mediated by the NO signal. PMID:26213372

Effect of exercise training and food restriction on endothelium-dependent relaxation in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous NIDDM.

PubMed

Sakamoto, S; Minami, K; Niwa, Y; Ohnaka, M; Nakaya, Y; Mizuno, A; Kuwajima, M; Shima, K

1998-01-01

We investigated whether endothelial function may be impaired in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous NIDDM. The effect of exercise training and food restriction on endothelial function was also studied. OLETF rats were divided into three groups at age 16 weeks: sedentary, exercise trained, and food restricted (70% of the food intake of sedentary rats). Otsuka Long-Evans Tokushima rats were used as the age-matched nondiabetic controls. Endothelium-dependent relaxation of the thoracic aorta induced by histamine was significantly attenuated in the sedentary or food-restricted rats, and exercise training improved endothelial function. Relaxation induced by sodium nitroprusside, a donor of nitric oxide, did not differ significantly among groups. Both exercise training and food restriction significantly suppressed plasma levels of glucose and insulin and serum levels of triacylglycerol and cholesterol and reduced the accumulation of abdominal fat. Insulin sensitivity, as measured by the hyperinsulinemic-euglycemic clamp technique, was significantly decreased in sedentary rats but was enhanced in exercise-trained and food-restricted rats. The urinary excretion of nitrite was significantly decreased in sedentary and food-restricted rats compared with nondiabetic rats and was significantly increased in exercise-trained rats. These results indicate that exercise training, but not food restriction, prevents endothelial dysfunction in NIDDM rats, presumably due to the exercise-induced increase in the production of nitric oxide.

Mesencephalic neuron death induced by congeners of nitrogen monoxide is prevented by the lazaroid U-83836E.

PubMed

Grasbon-Frodl, E M; Brundin, P

1997-01-01

We explored the effects of congeners of nitrogen monoxide (NO) on cultured mesencephalic neurons. Sodium nitroprusside (SNP) was used as a donor of NO, the congeners of which have been found to exert either neurotoxic or neuroprotective effects depending on the surrounding redox milieu. In contrast to a previous report that suggests that the nitrosonium ion (NO+) is neuroprotective to cultured cortical neurons, we found that the nitrosonium ion reduces the survival of cultured dopamine neurons to 32% of control. There was a trend for further impairment of dopamine neuron survival, to only 7% of untreated control, when the cultures were treated with SNP plus ascorbate, i.e. when the nitric oxide radical (NO.) had presumably been formed. We also evaluated the effects of an inhibitor of lipid peroxidation, the lazaroid U-83836E, against SNP toxicity. U-83836E exerted marked neuroprotective effects in both insult models. More than twice as many dopamine neurons (75% of control) survived when the lazaroid was added to SNP-treated cultures and the survival was increased eight-fold (to 55% of control) when U-83836E was added to cultures treated with SNP plus ascorbate. We conclude that the congeners of NO released by SNP are toxic to mesencephalic neurons in vitro and that the lazaroid U-83836E significantly increases the survival of dopamine neurons in situations where congeners of NO are generated.

Microvascular endothelial function and severity of primary open angle glaucoma.

PubMed

Bukhari, S M I; Kiu, K Y; Thambiraja, R; Sulong, S; Rasool, A H G; Liza-Sharmini, A T

2016-12-01

PurposeThe role of microvascular endothelial dysfunction on severity of primary open angle glaucoma (POAG) was investigated in this study.Patients and methodsA prospective cohort study was conducted. One hundred and fourteen ethnically Malay patients (114 eyes) with POAG treated at the eye clinic of Hospital University Sains Malaysia between April 2012 and December 2014 were recruited. Patients aged between 40 and 80 years with two consecutive reliable and reproducible Humphrey visual field 24-2 analyses were selected. Patients who were diagnosed with any other type of glaucoma, previous glaucoma-filtering surgery, or other surgeries except uncomplicated cataract and pterygium surgery were excluded. Humphrey visual field analysis 24-2 was used to stratify the severity of glaucoma using Advanced Glaucoma Intervention Study (AGIS) score at the time of recruitment. Microvascular endothelial function was assessed using Laser Doppler fluximetry and iontophoresis. Iontophoresis process with acetylcholine (ACh) and sodium nitroprusside (SNP) was used to measure microvascular endothelium-dependent and -independent vasodilatation, respectively.ResultsBased on the AGIS score, 55 patients showed mild glaucoma, with 29 moderate and 30 severe. There was statistically significant difference in microvascular endothelial function (ACh% and ACh max ) between mild and moderate POAG cases (P=0.023) and between mild and severe POAG cases (P<0.001). There was negative correlation between microvascular endothelial function and severity of POAG (r=-0.457, P<0.001).ConclusionMicrovascular endothelial dysfunction may have a role in influencing the severity of POAG in Malay patients.

Definitions of differences and changes in peritoneal membrane water transport properties.

PubMed

Widerøe, T E; Smeby, L C; Dahl, K; Jörstad, S

1988-06-01

A survey is given comparing measurements of transperitoneal water transport in different clinical situations with analyses based on the so-called "pore theory." This model links the measured changes to physical alterations of the peritoneal membrane. The calculations include "equivalent pore radius," effective "membrane area" and diffusive length, the transport resistance of the unstirred dialysate layer, and the residual intraperitoneal volume after dialysate drainage. The clinical appearances include individual differences in transperitoneal transport characteristics, changes in transperitoneal transport over time on continuous ambulatory peritoneal dialysis (CAPD) and during peritonitis, the pharmacological effect on the transport properties, and the effect of peritoneal catheter dislocation on ultrafiltration capacity. The main conclusions are as follow: During CAPD treatment the measurement of intraperitoneal solute equilibration and "mass-transfer-area coefficients" for urea and creatinine is less sensitive than the measurement of ultrafiltration volume in revealing peritoneal membrane changes. Differences and changes found have mostly a combined physical explanation, but one is more or less dominant. Changes in peritoneal membrane area seem to be the most dominant cause of changes in transperitoneal transport during time on CAPD and when sodium nitroprusside was added to the peritoneal dialysate. Changes during peritonitis can be explained by changes in pore radius and depth. Individual differences can be explained by differences in "membrane" area and in resistance of the unstirred dialysate fluid. High residual dialysate volume can give rise to clinical problems and should be considered when placing the catheter in the peritoneal cavity.

Berberine prevents nitric oxide-induced rat chondrocyte apoptosis and cartilage degeneration in a rat osteoarthritis model via AMPK and p38 MAPK signaling.

PubMed

Zhou, Yan; Liu, Shi-Qing; Yu, Ling; He, Bin; Wu, Shi-Hao; Zhao, Qi; Xia, Shao-Qiang; Mei, Hong-Jun

2015-09-01

Chondrocyte apoptosis is an important mechanism involved in osteoarthritis (OA). Berberine (BBR), a plant alkaloid derived from Chinese medicine, is characterized by multiple pharmacological effects, such as anti-inflammatory and anti-apoptotic activities. This study aimed to evaluate the chondroprotective effect and underlying mechanisms of BBR on sodium nitroprusside (SNP)-stimulated chondrocyte apoptosis and surgically-induced rat OA model. The in vitro results revealed that BBR suppressed SNP-stimulated chondrocyte apoptosis as well as cytoskeletal remodeling, down-regulated expressions of inducible nitric oxide synthase (iNOS) and caspase-3, and up-regulated Bcl-2/Bax ratio and Type II collagen (Col II) at protein levels, which were accompanied by increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and decreased phosphorylation of p38 mitogen-activated protein kinase (MAPK). Furthermore, the anti-apoptotic effect of BBR was blocked by AMPK inhibitor Compound C (CC) and adenosine-9-β-D-arabino-furanoside (Ara A), and enhanced by p38 MAPK inhibitor SB203580. In vivo experiment suggested that BBR ameliorated cartilage degeneration and exhibited an anti-apoptotic effect on articular cartilage in a rat OA model, as demonstrated by histological analyses, TUNEL assay and immunohistochemical analyses of caspase-3, Bcl-2 and Bax expressions. These findings suggest that BBR suppresses SNP-stimulated chondrocyte apoptosis and ameliorates cartilage degeneration via activating AMPK signaling and suppressing p38 MAPK activity.

Effects of fenspiride on human bronchial cyclic nucleotide phosphodiesterase isoenzymes: functional and biochemical study.

PubMed

Cortijo, J; Naline, E; Ortiz, J L; Berto, L; Girard, V; Malbezin, M; Advenier, C; Morcillo, E J

1998-01-02

We have investigated the role of human bronchial cyclic nucleotide phosphodiesterases in the effects of fenspiride, a drug endowed with bronchodilator and anti-inflammatory properties. Functional studies on human isolated bronchi showed that fenspiride (10(-6)-3 x 10(-3) M, 30 min) induced a shift to the left of the concentration-response curves for isoprenaline and sodium nitroprusside with -logEC50 values of 4.1+/-0.1 (n = 7) and 3.5+/-0.2 (n = 8), respectively. Biochemical studies were carried out on three human bronchi in which separation of cyclic nucleotide phosphodiesterase isoenzymes was performed by ion exchange chromatography followed by determination of phosphodiesterase activity with a radioisotopic method. Phosphodiesterase 4 (cyclic AMP-specific) and phosphodiesterase 5 (cyclic GMP-specific) were the major phosphodiesterase isoforms present in the human bronchial tissue. The presence of phosphodiesterase 1 (Ca2+/calmodulin-stimulated), phosphodiesterase 2 (cyclic GMP-stimulated) and, in two cases, phosphodiesterase 3 (cyclic GMP-inhibited) was also identified. Fenspiride inhibited phosphodiesterase 4 and phosphodiesterase 3 activities with -logIC50 values of 4.16+/-0.09 and 3.44+/-0.12, respectively. Phosphodiesterase 5 activity was also inhibited with a -logIC50 value of approximately 3.8. Fenspiride (< or = 10(-3) M) produced less than 25% inhibition of phosphodiesterase 1 and phosphodiesterase 2 activities. In conclusion, fenspiride is an effective inhibitor of both cyclic AMP and cyclic GMP hydrolytic activity in human bronchial tissues and this action may contribute to its airway effects.

Increased renal sympathetic nerve activity leads to hypertension and renal dysfunction in offspring from diabetic mothers.

PubMed

de Almeida Chaves Rodrigues, Aline Fernanda; de Lima, Ingrid Lauren Brites; Bergamaschi, Cássia Toledo; Campos, Ruy Ribeiro; Hirata, Aparecida Emiko; Schoorlemmer, Guus Hermanus Maria; Gomes, Guiomar Nascimento

2013-01-15

The exposure of the fetus to a hyperglycemic environment promotes the development of hypertension and renal dysfunction in the offspring at adult age. We evaluated the role of renal nerves in the hypertension and renal changes seen in offspring of diabetic rats. Diabetes was induced in female Wistar rats (streptozotocin, 60 mg/kg ip) before mating. Male offspring from control and diabetic dams were studied at an age of 3 mo. Systolic blood pressure measured by tail cuff was increased in offspring of diabetic dams (146 ± 1.6 mmHg, n = 19, compared with 117 ± 1.4 mmHg, n = 18, in controls). Renal function, baseline renal sympathetic nerve activity (rSNA), and arterial baroreceptor control of rSNA were analyzed in anesthetized animals. Glomerular filtration rate, fractional sodium excretion, and urine flow were significantly reduced in offspring of diabetic dams. Two weeks after renal denervation, blood pressure and renal function in offspring from diabetic dams were similar to control, suggesting that renal nerves contribute to sodium retention in offspring from diabetic dams. Moreover, basal rSNA was increased in offspring from diabetic dams, and baroreceptor control of rSNA was impaired, with blunted responses to infusion of nitroprusside and phenylephrine. Thus, data from this study indicate that in offspring from diabetic mothers, renal nerves have a clear role in the etiology of hypertension; however, other factors may also contribute to this condition.

A Systematic Review of Topical Vasodilators for the Treatment of Intraoperative Vasospasm in Reconstructive Microsurgery.

PubMed

Vargas, Christina R; Iorio, Matthew L; Lee, Bernard T

2015-08-01

Intraoperative vasospasm during reconstructive microsurgery is common, often unpredictable, and potentially devastating with regard to flap survival. Current methods of pharmacologic management vary, and may be shifting as a result of changes in the availability of individual medications. This review aims to provide a concise examination of the published literature regarding use, efficacy, and adverse effects of the agents described for local management of vascular spasm during microsurgery. A systematic review of the literature was performed to identify articles relevant to pharmacologic treatment of intraoperative vasospasm in vivo. An additional review of the literature was performed with regard to each agent identified in order to provide clinical background information. Systematic review identified 20 articles, in which 14 vasodilator agents were evaluated. Drugs were classified into five pharmacologic categories: phosphodiesterase inhibitors (papaverine, pentoxifylline, and amrinone), local anesthetics (lidocaine), calcium channel blockers (nicardipine, verapamil, nifedipine, and magnesium sulfate), direct vasodilators (sodium nitroprusside, prostaglandin E1, nitroglycerin, and hydralazine), and alpha antagonists (phentolamine and chlorpromazine). Despite a variety of methods, these studies indicate some degree of experimental evidence of efficacy for each of these agents. Available literature regarding use of topical vasodilating agents for intraoperative management of vasospasm during microsurgery is limited and largely based on animal models, which may not reliably generalize to the reconstructive patient population. Well-controlled translational study in clinically applicable and reproducible models is needed to guide evidence-based clinical management of this important phenomenon.

Sustained release effects of berberine-loaded chitosan microspheres on in vitro chondrocyte culture.

PubMed

Zhou, Yan; Liu, Shiqing; Ming, Jianghua; Li, Yaming; Deng, Ming; He, Bin

2017-10-01

The low bioavailability and short biological half-life of berberine chloride (BBR) negatively affect the protective role of this compound against osteoarthritis (OA). The present study was performed to evaluate the effectiveness of sustained BBR release system. Novel BBR-loaded chitosan microspheres (BBR-loaded CMs) were successfully synthesized using an ionic cross-linking method for sustained release. The basic characteristics of the prepared microspheres were subsequently evaluated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) techniques, encapsulation efficiency (EE), and in vitro release experiments. BBR-loaded CMs displayed spherical forms to encapsulate a considerable quantity of BBR (100.8 ± 2.7 mg/g); these microspheres also exhibited an ideal releasing profile. The FT-IR spectra and XRD results revealed that BBR-loaded CMs were successfully synthesized via electrostatic interaction. In vitro experiments further showed that BBR-loaded CMs significantly inhibited sodium nitroprusside (SNP)-stimulated chondrocyte apoptosis as well as cytoskeletal remodeling, and led to increasing mitochondrial membrane potential and maintaining the nuclear morphology. BBR-loaded CMs exerted markedly higher anti-apoptotic activity in the treatment of OA, and markedly inhibited the protein expression levels of caspase-3, a disintegrin, and metalloproteinase with thrombospondin motifs (ADAMTS)-5 and matrix metalloproteinase (MMP)-13 induced by SNP in rat articular chondrocytes, compared with free BBR at equivalent concentration. Therefore, novel BBR-loaded CMs may offer potential for application in the treatment of OA.

Glu298Asp polymorphism influences the beneficial effects of fish oil fatty acids on postprandial vascular function[S

PubMed Central

Thompson, Abby K.; Newens, Katie J.; Jackson, Kim G.; Wright, John; Williams, Christine M.

2012-01-01

Our objective was to determine whether the endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism influences vascular response to raised NEFA enriched with saturated fatty acids (SFA) or long-chain (LC) n-3 polyunsaturated fatty acids (PUFA). Subjects were prospectively recruited for genotype (Glu298, n = 30 and Asp298, n = 29; balanced for age and gender) consumed SFA on two occasions, with and without the substitution of 0.07 g fat/kg body weight with LC n-3 PUFA, and with heparin infusion to elevate NEFA. Endothelial function was measured before and after NEFA elevation (240 min), with blood samples taken every 30 min. Flow-mediated dilation (FMD) decreased following SFA alone and increased following SFA+LC n-3 PUFA. There were 2-fold differences in the change in FMD response to the different fat loads between the Asp298 and Glu298 genotypes (P = 0.002) and between genders (P < 0.02). Sodium nitroprusside-induced reactivity, measured by laser Doppler imaging with iontophoresis, was significantly greater with SFA+LC n-3 PUFA in all female subjects (P < 0.001) but not in males. Elevated NEFA influences both endothelial-dependent and endothelial-independent vasodilation during the postprandial phase. Effects of fat composition appear to be genotype and gender dependent, with the greatest difference in vasodilatory response to the two fat loads seen in the Asp298 females. PMID:22847178

Effects of nitric oxide and its congeners on sickle red blood cell deformability.

PubMed

Belanger, Andrea M; Keggi, Christian; Kanias, Tamir; Gladwin, Mark T; Kim-Shapiro, Daniel B

2015-10-01

Sickle cell disease (SCD) is characterized by hemoglobin polymerization upon deoxygenation. Polymerization causes the sickle cells to become rigid and misshapen (sickling). Red blood cell (RBC) dehydration greatly increases polymerization. Cycles of sickling and unsickling cause an influx of calcium that leads to loss of potassium via the calcium-activated Gardos channel, which dehydrates the cells leading to increased polymerization. In this study the effects of nitric oxide (NO) and its congeners on RBC deformability were examined, focusing on sickle RBCs (sRBCs). RBCs from patients with SCD and from nonpatients were exposed to various compounds that release NO or its congeners. Intracellular calcium was increased using a calcium ionophore or cycling of oxygen tension for sRBCs. Deformability was measured by laser-assisted osmotic gradient ektacytometry. Consistent with a previous report, sodium nitroprusside (SNP) was found to protect against calcium-induced loss of deformability in normal RBCs, but (contrary to some previous reports) no effect of any NO donors was observed when calcium influx was not induced. Importantly, in studies of deoxygenation-induced dehydration of sRBCs, SNP resulted in substantial improvements in deformability (p = 0.036) and hydration (p = 0.024). Sodium nitrite showed similar trends. SNP was shown to have no effect on calcium influx, but reduced potassium efflux. These data suggest that SNP and perhaps certain nitrogen oxides (like nitrite) inhibit the Gardos channel and may be able to protect sickle cells from dehydration and thereby improve outcome in the disease. © 2015 AABB.

Nitric oxide mitigates the effect of water deficit in Crambe abyssinica.

PubMed

Batista, Priscila Ferreira; Costa, Alan Carlos; Müller, Caroline; Silva-Filho, Robson de Oliveira; Barbosa da Silva, Fábia; Merchant, Andrew; Mendes, Giselle Camargo; Nascimento, Kelly Juliane Telles

2018-06-12

Crambe abyssinica is widely cultivated in the off-season in the Midwest region of Brazil with great potential for biodeisel production. Low precipitation is characteristic of this region, which can drastically affect the productivity of C. abyssinica. Signaling molecules, such as nitric oxide (NO), can potentially alleviate the effects of water stress on plants. Here we test whether nitric oxide, applied by donor sodium nitroprusside (SNP), can alleviate the occurrence of water deficit damages in Crambe plants and maintain physiological and biochemical processes. Crambe plants were sprayed with three doses of SNP (0, 75, and 150 μM) and were submitted to two water levels (100% and 50% of the maximum water holding capacity). After 32 and 136 h, leaves were analyzed to evaluate the concentration of NO, water relations, gas exchange, chlorophyll a fluorescence, chloroplastidic pigments, proline, malondialdehyde, hydrogen peroxide, superoxide anions, and the antioxidant enzymes activity. Application of SNP allowed the maintenance of gas exchange, chlorophyll fluorescence parameters, and activities of antioxidant enzymes in plants exposed to water deficit, as well as increased the concentration of NO, proline, chloroplastidic pigments and osmotic potential. The application of SNP also decreased the concentration of malondialdehyde and reactive oxygen species in plants submitted to water deficit. Thus, the application of SNP prevented the occurrence of symptoms of water deficit in Crambe plants, maintaining the physiological and biochemical responses at reference levels, even under stress conditions. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The inhibition of inducible nitric oxide synthase and oxidative stress by agmatine attenuates vascular dysfunction in rat acute endotoxemic model.

PubMed

El-Awady, Mohammed S; Nader, Manar A; Sharawy, Maha H

2017-10-01

Vascular dysfunction leading to hypotension is a major complication in patients with septic shock. Inducible nitric oxide synthase (iNOS) together with oxidative stress play an important role in development of vascular dysfunction in sepsis. Searching for an endogenous, safe and yet effective remedy was the chief goal for this study. The current study investigated the effect of agmatine (AGM), an endogenous metabolite of l-arginine, on sepsis-induced vascular dysfunction induced by lipopolysaccharides (LPS) in rats. AGM pretreatment (10mg/kg, i.v.) 1h before LPS (5mg/kg, i.v.) prevented the LPS-induced mortality and elevations in serum creatine kinase-MB isoenzyme (CK-MB) activity, lactate dehydrogenase (LDH) activity, C-reactive protein (CRP) level and total nitrite/nitrate (NOx) level after 24h from LPS injection. The elevation in aortic lipid peroxidation illustrated by increased malondialdehyde (MDA) content and the decrease in aortic glutathione (GSH) and superoxide dismutase (SOD) were also ameliorated by AGM. Additionally, AGM prevented LPS-induced elevation in mRNA expression of iNOS, while endothelial NOS (eNOS) mRNA was not affected. Furthermore AGM prevented the impaired aortic contraction to KCl and phenylephrine (PE) and endothelium-dependent relaxation to acetylcholine (ACh) without affecting endothelium-independent relaxation to sodium nitroprusside (SNP). AGM may represent a potential endogenous therapeutic candidate for sepsis-induced vascular dysfunction through its inhibiting effect on iNOS expression and oxidative stress. Copyright © 2017 Elsevier B.V. All rights reserved.

In vitro antioxidant activity of Valeriana officinalis against different neurotoxic agents.

PubMed

Sudati, Jéssie Haigert; Fachinetto, Roselei; Pereira, Romaiana Picada; Boligon, Aline Augusti; Athayde, Margareth Linde; Soares, Felix Antunes; de Vargas Barbosa, Nilda Berenice; Rocha, João Batista Teixeira

2009-08-01

Valeriana officinalis L. (Valerian) is widely used as a traditional medicine to improve the quality of sleep. Although V. officinalis have been well documented as promising pharmacological agent; the exact mechanisms by which this plant act is still unknown. Limited literature data have indicated that V. officinalis extracts can exhibit antioxidant properties against iron in hippocampal neurons in vitro. However, there is no data available about the possible antioxidant effect of V. officinalis against other pro-oxidants in brain. In the present study, the protective effect of V. officinalis on lipid peroxidation (LPO) induced by different pro-oxidant agents with neuropathological importance was examined. Ethanolic extract of valerian (0-60 microg/ml) was tested against quinolinic acid (QA); 3-nitropropionic acid; sodium nitroprusside; iron sulfate (FeSO4) and Fe2+/EDTA induced LPO in rat brain homogenates. The effect of V. officinalis in deoxyribose degradation and reactive oxygen species (ROS) production was also investigated. In brain homogenates, V. officinalis inhibited thiobarbituric acid reactive substances induced by all pro-oxidants tested in a concentration dependent manner. Similarly, V. officinalis caused a significant decrease on the LPO in cerebral cortex and in deoxyribose degradation. QA-induced ROS production in cortical slices was also significantly reduced by V. officinalis. Our results suggest that V. officinalis extract was effective in modulating LPO induced by different pro-oxidant agents. These data may imply that V. officinalis extract, functioning as antioxidant agent, can be beneficial for reducing insomnia complications linked to oxidative stress.

Effects of One Resistance Exercise Session on Vascular Smooth Muscle of Hypertensive Rats

PubMed Central

da Silva, Tharciano Luiz Teixeira Braga; Mota, Marcelo Mendonça; Fontes, Milene Tavares; Araújo, João Eliakim dos Santos; Carvalho, Vitor Oliveira; Bonjardim, Leonardo Rigoldi; Santos, Márcio Roberto Viana

2015-01-01

Background Hypertension is a public health problem and increases the incidence of cardiovascular diseases. Objective To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of NG-nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats. Methods Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP). Results Rats treated with L-NAME showed an increase (p < 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001) the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01) smooth muscle sensitivity to NPS was observed in group EH as compared to group H. Conclusion One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats. PMID:26107814

Effects of one resistance exercise session on vascular smooth muscle of hypertensive rats.

PubMed

Silva, Tharciano Luiz Teixeira Braga da; Mota, Marcelo Mendonça; Fontes, Milene Tavares; Araújo, João Eliakim Dos Santos; Oliveira Carvalho, Vitor; Bonjardim, Leonardo Rigoldi; Santos, Márcio Roberto Viana

2015-08-01

Hypertension is a public health problem and increases the incidence of cardiovascular diseases. To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of NG-nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats. Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP). Rats treated with L-NAME showed an increase (p < 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001) the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01) smooth muscle sensitivity to NPS was observed in group EH as compared to group H. One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.

Targeted ablation of cardiac sympathetic neurons reduces resting, reflex and exercise-induced sympathetic activation in conscious rats.

PubMed

Lujan, Heidi L; Palani, Gurunanthan; Chen, Ying; Peduzzi, Jean D; Dicarlo, Stephen E

2009-05-01

Cholera toxin B subunit conjugated to saporin (SAP, a ribosomal inactivating protein that binds to and inactivates ribosomes) was injected in both stellate ganglia to evaluate the physiological response to targeted ablation of cardiac sympathetic neurons. Resting cardiac sympathetic activity (cardiac sympathetic tonus), exercise-induced sympathetic activity (heart rate responses to graded exercise), and reflex sympathetic activity (heart rate responses to graded doses of sodium nitroprusside, SNP) were determined in 18 adult conscious Sprague-Dawley male rats. Rats were randomly divided into the following three groups (n = 6/group): 1) control (no injection), 2) bilateral stellate ganglia injection of unconjugated cholera toxin B (CTB), and 3) bilateral stellate ganglia injection of cholera toxin B conjugated to SAP (CTB-SAP). CTB-SAP rats, compared with control and CTB rats, had reduced cardiac sympathetic tonus and reduced heart rate responses to graded exercise and graded doses of SNP. Furthermore, the number of stained neurons in the stellate ganglia and spinal cord (segments T(1)-T(4)) was reduced in CTB-SAP rats. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing resting, exercise, and reflex sympathetic activity. Additional studies are required to further characterize the physiological responses to this procedure as well as determine if this new approach is safe and efficacious for the treatment of conditions associated with excess sympathetic activity (e.g., autonomic dysreflexia, hypertension, heart failure, and ventricular arrhythmias).

Influence of respiratory motor neurone activity on human autonomic and haemodynamic rhythms

NASA Technical Reports Server (NTRS)

Gonschorek, A. S.; Lu, L. L.; Halliwill, J. R.; Beightol, L. A.; Taylor, J. A.; Painter, J. A.; Warzel, H.; Eckberg, D. L.

2001-01-01

Although humans hold great advantages over other species as subjects for biomedical research, they also bring major disadvantages. One is that among the many rhythmic physiological signals that can be recorded, there is no sure way to know which individual change precedes another, or which change represents cause and which represents effect. In an attempt to deal with the inherent complexity of research conducted in intact human subjects, we developed and used a structural equation model to analyse responses of healthy young men to pharmacological changes of arterial pressure and graded inspiratory resistance, before and after vagomimetic atropine. Our model yielded a good fit of the experimental data, with a system weighted R2 of 0.77, and suggested that our treatments exerted both direct and indirect influences on the variables we measured. Thus, infusions of nitroprusside and phenylephrine exerted all of their direct effects by lowering and raising arterial pressure; the changes of R-R intervals, respiratory sinus arrhythmia and arterial pressure fluctuations that these drugs provoked, were indirect consequences of arterial pressure changes. The only direct effect of increased inspiratory resistance was augmentation of arterial pressure fluctuations. These results may provide a new way to disentangle and understand responses of intact human subjects to experimental forcings. The principal new insight we derived from our modelling is that respiratory gating of vagal-cardiac motor neurone firing is nearly maximal at usual levels of arterial pressure and inspiratory motor neurone activity.

Nitric oxide (NO) in normal and hypoxic vascular regulation of the spiny dogfish, Squalus acanthias.

PubMed

Swenson, Kai E; Eveland, Randy L; Gladwin, Mark T; Swenson, Erik R

2005-02-01

Nitric oxide (NO) is a potent vasodilator in terrestrial vertebrates, but whether vascular endothelial-derived NO plays a role in vascular regulation in fish remains controversial. To explore this issue, a study was made of spiny dogfish sharks (Squalus acanthias) in normoxia and acute hypoxia (60 min exposure to seawater equilibrated with 3% oxygen) with various agents known to alter NO metabolism or availability. In normoxia, nitroprusside (a NO donor) reduced blood pressure by 20%, establishing that vascular smooth muscle responds to NO. L-arginine, the substrate for NO synthase, had no hemodynamic effect. Acetylcholine, which stimulates endothelial NO and prostaglandin production in mammals, reduced blood pressure, but also caused marked bradycardia. L-NAME, an inhibitor of all NO synthases, caused a small 10% rise in blood pressure, but cell-free hemoglobin (a potent NO scavenger and hypertensive agent in mammals) had no effect. Acute hypoxia caused a 15% fall in blood pressure, which was blocked by L-NAME and cell-free hemoglobin. Serum nitrite, a marker of NO production, rose with hypoxia, but not with L-NAME. Results suggest that NO is not an endothelial-derived vasodilator in the normoxic elasmobranch. The hypertensive effect of L-NAME may represent inhibition of NO production in the CNS and nerves regulating blood pressure. In acute hypoxia, there is a rapid up-regulation of vascular NO production that appears to be responsible for hypoxic vasodilation.

Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle

PubMed Central

2012-01-01

Background Cigarette exposure increases brain oxidative stress. The literature showed that increased brain oxidative stress affects cardiovascular regulation. However, no previous study investigated the involvement of brain oxidative stress in animals exposed to cigarette and its relationship with cardiovascular regulation. We aimed to evaluate the effects of central catalase inhibition on baroreflex and cardiovascular responses in rats exposed to sidestream cigarette smoke (SSCS). Methods We evaluated males Wistar rats (320-370 g), which were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). Femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. Rats were exposed to SSCS during three weeks, 180 minutes, 5 days/week (CO: 100-300 ppm). Baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 μg/kg, bolus) to induce bradycardic reflex and a depressor dose of sodium nitroprusside (SNP, 50 μg/kg, bolus) to induce tachycardic reflex. Cardiovascular responses were evaluated before, 5, 15, 30 and 60 minutes after 3-amino-1,2,4-triazole (ATZ, catalase inhibitor, 0.001 g/100 μL) injection into the 4th V. Results Central catalase inhibition increased basal HR in the control group during the first 5 minutes. SSCS exposure increased basal HR and attenuated bradycardic peak during the first 15 minutes. Conclusion We suggest that SSCS exposure affects cardiovascular regulation through its influence on catalase activity. PMID:22463380

Nitric oxide acts upstream of ethylene in cell wall phosphorus reutilization in phosphorus-deficient rice.

PubMed

Zhu, Xiao Fang; Zhu, Chun Quan; Wang, Chao; Dong, Xiao Ying; Shen, Ren Fang

2017-01-01

Nitric oxide (NO) and ethylene are both involved in cell wall phosphorus (P) reutilization in P-deficient rice; however, the crosstalk between them remains unclear. In the present study using P-deficient 'Nipponbare' (Nip), root NO accumulation significantly increased after 1 h and reached a maximum at 3 h, while ethylene production significantly increased after 3 h and reached a maximum at 6 h, indicating NO responded more quickly than ethylene. Irrespective of P status, addition of the NO donor sodium nitroprusside (SNP) significantly increased while the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO) significantly decreased the production of ethylene, while neither the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) nor the ethylene inhibitor aminoethoxyvinylglycine (AVG) had any influence on NO accumulation, suggesting NO acted upstream of ethylene. Under P-deficient conditions, SNP and ACC alone significantly increased root soluble P content through increasing pectin content, and c-PTIO addition to the ACC treatment still showed the same tendency; however, AVG+SNP treatment had no effect, further indicating that ethylene was the downstream signal affecting pectin content. The expression of the phosphate transporter gene OsPT2 showed the same tendency as the NO-ethylene-pectin pathway. Taken together, we conclude that ethylene functions downstream of NO in cell wall P reutilization in P-deficient rice. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Comparative study of flux of FITC-labeled Dextran 4000 on normal (iso)- and hyper-osmolarity in basal side in caco-2 cell monolayers.

PubMed

Ohkubo, Rie; Tomita, Mikio; Hotta, Yoshiyuki; Nagira, Mayuko; Hayashi, Masahiro

2003-01-01

We have shown previously that the flux of fluorescein isothiocyanate dextran 4000 (FD-4) is transported across the Caco-2 cell monolayers in a polarized fashion favoring the basal to apical direction under normal conditions (i.e., isotonic solution in basal side). Furthermore, FD-4 transport may occur via a process that included a certain degree of substrate specificity for polysaccharide and transcytosis. In the present study, we compared the flux of FD-4 in the basal to apical direction (efflux) and the apical to basal direction (influx) in stress conditions (i.e., hyperosmolarity in basal side) to those in normal conditions (i.e., iso-osmolarity in basal side). The efflux of FD-4 was increased by hyperosmolarity in basal side, but the influx was decreased when compared with normal conditions. Neither dextran 10, 000 nor colchicine inhibited the efflux of FD-4 in hyperosmolarity conditions. The inhibition of efflux of FD-4 was observed not by S-nitroso-N-acetylpenicillamine but by sodium nitroprusside and sodium ferrocyanide. These results collectively suggest that hyperosmolarity in basal side accelerates the efflux of FD-4 across the transcellular route but not across the paracellular route in Caco-2 cell monolayers. And it is indicated that cyanide rather than nitric oxide is involved in dysfunction of the FD-4 efflux system irrespective of conditions such as normal osmolarity or hyperosmolarity.

Cytotoxicity of nitric oxide in Fu5 rat hepatoma cells: evidence for co-operative action with hydrogen peroxide.

PubMed Central

Ioannidis, I; de Groot, H

1993-01-01

The NO-releasing compounds 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1), sodium nitroprusside (SNP) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) mediated a rapid loss of viability of Fu5 rat hepatoma cells. SIN-1 in addition to NO also released the superoxide anion radical (O2-.). Its cytotoxicity, however, was not affected by superoxide dismutase. In contrast, the H2O2-converting enzyme catalase significantly, but not completely, diminished cell damage, indicating participation of H2O2 in the tumoricidal activity of SIN-1. Glucose oxidase (5 m-units/ml), producing similar amounts of H2O2 to 5 mM SIN-1, had no effect on cell viability. When 5 m-units/ml glucose oxidase was added to incubations with 5 mM SNP, which alone initiated cell injury of about 40%, cell damage was significantly increased up to 95%. Similar results were observed with 1 mM SNAP and 20 m-units/ml xanthine oxidase, which mediated cytotoxicity of about 90% when both compounds were added together, compared with 35% and 55% cell injury, respectively, induced by the single compounds. The results indicate that a co-operative action with H2O2 enhances the tumoricidal activity of NO in Fu5 cells. No evidence for an interplay of NO with O2-. in cytotoxicity, e.g. via the peroxynitrite anion (ONOO-), was found. PMID:8257422

Isovolumic relaxation period as an index of left ventricular relaxation under different afterload conditions--comparison with the time constant of left ventricular pressure decay in the dog.

PubMed

Ochi, H; Ikuma, I; Toda, H; Shimada, T; Morioka, S; Moriyama, K

1989-12-01

In order to determine whether isovolumic relaxation period (IRP) reflects left ventricular relaxation under different afterload conditions, 17 anesthetized, open chest dogs were studied, and the left ventricular pressure decay time constant (T) was calculated. In 12 dogs, angiotensin II and nitroprusside were administered, with the heart rate constant at 90 beats/min. Multiple linear regression analysis showed that the aortic dicrotic notch pressure (AoDNP) and T were major determinants of IRP, while left ventricular end-diastolic pressure was a minor determinant. Multiple linear regression analysis, correlating T with IRP and AoDNP, did not further improve the correlation coefficient compared with that between T and IRP. We concluded that correction of the IRP by AoDNP is not necessary to predict T from additional multiple linear regression. The effects of ascending aortic constriction or angiotensin II on IRP were examined in five dogs, after pretreatment with propranolol. Aortic constriction caused a significant decrease in IRP and T, while angiotensin II produced a significant increase in IRP and T. IRP was affected by the change of afterload. However, the IRP and T values were always altered in the same direction. These results demonstrate that IRP is substituted for T and it reflects left ventricular relaxation even in different afterload conditions. We conclude that IRP is a simple parameter easily used to evaluate left ventricular relaxation in clinical situations.

Nitric Oxide Inhibits Al-Induced Programmed Cell Death in Root Tips of Peanut (Arachis hypogaea L.) by Affecting Physiological Properties of Antioxidants Systems and Cell Wall

PubMed Central

Pan, Chun-Liu; Yao, Shao-Chang; Xiong, Wei-Jiao; Luo, Shu-Zhen; Wang, Ya-Lun; Wang, Ai-Qin; Xiao, Dong; Zhan, Jie; He, Long-Fei

2017-01-01

It has been reported that nitric oxide (NO) is a negative regulator of aluminum (Al)-induced programmed cell death (PCD) in peanut root tips. However, the inhibiting mechanism of NO on Al-induced PCD is unclear. In order to investigate the mechanism by which NO inhibits Al-induced PCD, the effects of co-treatment Al with the exogenous NO donor or the NO-specific scavenger on peanut root tips, the physiological properties of antioxidants systems and cell wall (CW) in root tip cells of NO inhibiting Al-induced PCD were studied with two peanut cultivars. The results showed that Al exposure induced endogenous NO accumulation, and endogenous NO burst increased antioxidant enzyme activity in response to Al stress. The addition of NO donor sodium nitroprusside (SNP) relieved Al-induced root elongation inhibition, cell death and Al adsorption in CW, as well as oxidative damage and ROS accumulation. Furthermore, co-treatment with the exogenous NO donor decreased MDA content, LOX activity and pectin methylesterase (PME) activity, increased xyloglucan endotransglucosylase (XET) activity and relative expression of the xyloglucan endotransglucosylase/hydrolase (XTH-32) gene. Taken together, exogenous NO alleviated Al-induced PCD by inhibiting Al adsorption in CW, enhancing antioxidant defense and reducing peroxidation of membrane lipids, alleviating the inhibition of Al on root elongation by maintaining the extensibility of CW, decreasing PME activity, and increasing XET activity and relative XTH-32 expression of CW. PMID:29311970

Nitric Oxide Inhibits Al-Induced Programmed Cell Death in Root Tips of Peanut (Arachis hypogaea L.) by Affecting Physiological Properties of Antioxidants Systems and Cell Wall.

PubMed

Pan, Chun-Liu; Yao, Shao-Chang; Xiong, Wei-Jiao; Luo, Shu-Zhen; Wang, Ya-Lun; Wang, Ai-Qin; Xiao, Dong; Zhan, Jie; He, Long-Fei

2017-01-01

It has been reported that nitric oxide (NO) is a negative regulator of aluminum (Al)-induced programmed cell death (PCD) in peanut root tips. However, the inhibiting mechanism of NO on Al-induced PCD is unclear. In order to investigate the mechanism by which NO inhibits Al-induced PCD, the effects of co-treatment Al with the exogenous NO donor or the NO-specific scavenger on peanut root tips, the physiological properties of antioxidants systems and cell wall (CW) in root tip cells of NO inhibiting Al-induced PCD were studied with two peanut cultivars. The results showed that Al exposure induced endogenous NO accumulation, and endogenous NO burst increased antioxidant enzyme activity in response to Al stress. The addition of NO donor sodium nitroprusside (SNP) relieved Al-induced root elongation inhibition, cell death and Al adsorption in CW, as well as oxidative damage and ROS accumulation. Furthermore, co-treatment with the exogenous NO donor decreased MDA content, LOX activity and pectin methylesterase (PME) activity, increased xyloglucan endotransglucosylase (XET) activity and relative expression of the xyloglucan endotransglucosylase/hydrolase ( XTH-32 ) gene. Taken together, exogenous NO alleviated Al-induced PCD by inhibiting Al adsorption in CW, enhancing antioxidant defense and reducing peroxidation of membrane lipids, alleviating the inhibition of Al on root elongation by maintaining the extensibility of CW, decreasing PME activity, and increasing XET activity and relative XTH-32 expression of CW.

Hypertensive crisis with 2 target organ impairment induced by glycyrrhizin

PubMed Central

Li, Jing; Fan, Xiaoli; Wang, Qin

2018-01-01

Abstract Rationale: Glycyrrhizin is the main active component of licorice. Licorice and glycyrrhizin induced hypertension has been widely reported, yet licorice and glycyrrhizin induced hypertensive crisis has been rarely known. Patient concerns: The case of this report was a 47-year-old woman, who took 225 mg of glycyrrhizin daily for 3 years due to primary biliary cholangitis. She was found to have a dramatically elevated blood pressure of about 230/110 mmHg without a history of hypertension and was referred to the emergency department. Diagnoses: Hypokalemia, hypertensive retinopathy, and nephropathy were found during the following work-up. Since no other risk factors of hypertension were identified, she was suspected to have glycyrrhizin induced pseudo-hyperaldosteronism. Interventions: Glycyrrhizin was discontinued. Intravenous sodium nitroprusside was used during the first few days. Nifedipine and irbesartan were taken after discharge, and the dosage was reduced gradually under supervision. Outcomes: She stopped all the anti-hypertensive drugs 6 months since glycyrrhizin was stopped. Her blood pressure was about 110/60 mmHg after repetitive measurement. Her serum potassium and urine albumin/creatinine ratio were also normalized. Lessons: Licorice and glycyrrhizin induced hypertension due to pseudo-hyperaldosteronism has been widely reported, yet only 3 cases reported that excessive consumption of licorice could lead to hypertensive emergencies. This is the first case that glycyrrhizin induced hypertensive crisis with target organ impairment. By presenting this case, we remind clinicians of glycyrrhizin induced hypertension, a condition which could lead to medical emergencies. PMID:29538199

Dutch guideline for the management of hypertensive crisis -- 2010 revision.

PubMed

van den Born, B J H; Beutler, J J; Gaillard, C A J M; de Gooijer, A; van den Meiracker, A H; Kroon, A A

2011-05-01

Hypertensive crises are divided into hypertensive urgencies and emergencies. Together they form a heterogeneous group of acute hypertensive disorders depending on the presence or type of target organs involved. Despite better treatment options for hypertension, hypertensive crisis and its associated complications remain relatively common. In the Netherlands the number of patients starting renal replacement therapy because of 'malignant hypertension' has increased in the past two decades. In 2003, the first Dutch guideline on hypertensive crisis was released to allow a standardised evidence-based approach for patients presenting with a hypertensive crisis. In this paper we give an overview of the current management of hypertensive crisis and discuss several important changes incorporated in the 2010 revision. These changes include a modification in terminology replacing 'malignant hypertension' with 'hypertensive crisis with retinopathy and reclassification of hypertensive crisis with retinopathy under hypertensive emergencies instead of urgencies. With regard to the treatment of hypertensive emergencies, nicardipine instead of nitroprusside or labetalol is favoured for the management of perioperative hypertension, whereas labetalol has become the drug of choice for the treatment of hypertension associated with pre-eclampsia. For the treatment of hypertensive urgencies, oral administration of nifedipine retard instead of captopril is recommended as first-line therapy. In addition, a section on the management of hypertensive emergencies according to the type of target organ involved has been added. Efforts to increase the awareness and treatment of hypertension in the population at large may lower the incidence of hypertensive crisis and its complications.

Hypertensive crisis with 2 target organ impairment induced by glycyrrhizin: A case report.

PubMed

Li, Jing; Fan, Xiaoli; Wang, Qin

2018-03-01

Glycyrrhizin is the main active component of licorice. Licorice and glycyrrhizin induced hypertension has been widely reported, yet licorice and glycyrrhizin induced hypertensive crisis has been rarely known. The case of this report was a 47-year-old woman, who took 225 mg of glycyrrhizin daily for 3 years due to primary biliary cholangitis. She was found to have a dramatically elevated blood pressure of about 230/110 mmHg without a history of hypertension and was referred to the emergency department. Hypokalemia, hypertensive retinopathy, and nephropathy were found during the following work-up. Since no other risk factors of hypertension were identified, she was suspected to have glycyrrhizin induced pseudo-hyperaldosteronism. Glycyrrhizin was discontinued. Intravenous sodium nitroprusside was used during the first few days. Nifedipine and irbesartan were taken after discharge, and the dosage was reduced gradually under supervision. She stopped all the anti-hypertensive drugs 6 months since glycyrrhizin was stopped. Her blood pressure was about 110/60 mmHg after repetitive measurement. Her serum potassium and urine albumin/creatinine ratio were also normalized. Licorice and glycyrrhizin induced hypertension due to pseudo-hyperaldosteronism has been widely reported, yet only 3 cases reported that excessive consumption of licorice could lead to hypertensive emergencies. This is the first case that glycyrrhizin induced hypertensive crisis with target organ impairment. By presenting this case, we remind clinicians of glycyrrhizin induced hypertension, a condition which could lead to medical emergencies.

Contribution of Kv7 channels to natriuretic peptide mediated vasodilation in normal and hypertensive rats.

PubMed

Stott, Jennifer B; Barrese, Vincenzo; Jepps, Thomas A; Leighton, Emma V; Greenwood, Iain A

2015-03-01

The Kv7 family of voltage-gated potassium channels are expressed within the vasculature where they are key regulators of vascular tone and mediate cAMP-linked endogenous vasodilator responses, a pathway that is compromised in hypertension. However, the role of Kv7 channels in non-cAMP-linked vasodilator pathways has not been investigated. Natriuretic peptides are potent vasodilators, which operate primarily through the activation of a cGMP-dependent signaling pathway. This study investigated the putative role of Kv7 channels in natriuretic peptide-dependent relaxations in the vasculature of normal and hypertensive animals. Relaxant responses of rat aorta to both atrial and C-type natriuretic peptides and the nitric oxide donor sodium nitroprusside were impaired by the Kv7 blocker linopirdine (10 μmol/L) but not by the Kv7.1-specific blocker HMR1556 (10 μmol/L) and other K(+) channel blockers. In contrast, only the atrial natriuretic peptide response was sensitive to linopirdine in the renal artery. These Kv7-mediated responses were attenuated in arteries from hypertensive rats. Quantitative polymerase chain reaction showed that A- and B-type natriuretic peptide receptors were expressed at high levels in the aorta and renal artery from normal and spontaneously hypertensive rats. This study provides the first evidence that natriuretic peptide responses are impaired in hypertension and that recruitment of Kv7 channels is a key component of natriuretic peptide-dependent vasodilations. © 2014 American Heart Association, Inc.

Exposure to nitric oxide increases the nitrosyl-iron complexes content in sorghum embryonic axes.

PubMed

Simontacchi, Marcela; Buet, Agustina; Lamattina, Lorenzo; Puntarulo, Susana

2012-02-01

This work was aimed to investigate nitrosyl-Fe complexes formation by reaction of endogenous ligands and Fe, in sorghum embryonic axes exposed to NO-donors. Electron paramagnetic resonance (EPR) was employed to detect the presence of nitrosyl-Fe complexes in plant embryos, as well as changes in labile iron pool (LIP). Nitrosyl-Fe complexes formation was detected in sorghum embryonic axes homogenates incubated in vitro in the presence of 1 mM of NO donors: diethylenetriamine NONOate (DETA NONOate), S-nitrosoglutathione (GSNO) and sodium nitroprusside (SNP). In axes isolated from seeds incubated in vivo in the presence of 1 mM SNP for 24 h, the content of NO was increased by 2-fold, and the EPR spectrum from mononitrosyl-Fe complexes (MNIC) was observed with a concomitant increase in the fresh weight of sorghum axes. The simultaneous exposure to deferoxamine and the NO donor precluded the increase in fresh weight observed in the presence of excess NO. While total Fe content in the axes isolated from seeds exposed to 1mM SNP was not significantly affected as compared to control axes, the LIP was increased by over 2-fold.The data reported suggest a critical role for the generation of complexes between Fe and NO when cells faced a situation leading to a significant increase in NO content. Moreover, demonstrate the presence of MNICs as one of the important components of the LIP, which could actively participate in Fe cellular mobilization. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Rapid tachyphylaxis to hemodynamic effects of PACAP-27 after inhibition of nitric oxide synthesis

NASA Technical Reports Server (NTRS)

Whalen, E. J.; Travis, M. D.; Johnson, A. K.; Lewis, S. J.

1999-01-01

The vasodilator effects of pituitary adenylate cyclase-activating polypeptide (PACAP)-27 are subject to tachyphylaxis in rats treated with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). We examined whether this tachyphylaxis could be prevented by administration of the putative endothelium-derived nitrosyl factor S-nitroso-L-cysteine (L-SNC) and whether L-SNC may exert its effects via increases in cGMP levels in vascular smooth muscle. Five doses of PACAP-27 (2 nmol/kg iv) produced pronounced vasodilator responses in saline-treated rats. These responses were not subject to tachyphylaxis. The first injection of PACAP-27 (2 nmol/kg iv) in L-NAME-treated (50 micromol/kg iv) rats produced vasodilator responses similar to those in saline-treated rats, whereas subsequent injections produced progressively smaller responses. The injection of L-SNC (1,200 nmol/kg iv) before each injection of PACAP-27 prevented tachyphylaxis to the Gs protein-coupled receptor agonist in L-NAME-treated rats, whereas equihypotensive doses of the NO donor sodium nitroprusside (100 micrograms/kg iv) did not. The injection of the membrane-permeant cGMP analog 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-CPT-cGMP; 30 micromol/kg iv) to L-NAME-treated rats restored resting hemodynamic values to pre-L-NAME levels but did not prevent the development of tachyphylaxis to PACAP-27. These results suggest that nitrosyl factors prevent the development of tachyphylaxis to the hemodynamic actions of PACAP-27. These nitrosyl factors may act independently of their ability to generate cGMP in vascular smooth muscle.

Danshen attenuates osteoarthritis-related cartilage degeneration through inhibition of NF-κB signaling pathway in vivo and in vitro.

PubMed

Xu, Xilin; Lv, Hang; Li, Xiaodong; Su, Hui; Zhang, Xiaofeng; Yang, Jun

2017-12-01

Danshen (Salvia miltiorrhiza) is a traditional Chinese medicine herb that can alleviate the symptoms of osteoarthritis (OA) (Söder et al. 2006) in animals. However, the underlying mechanisms remain poorly understood and require further investigation. In this study, rabbits with experimentally induced OA were given an intra-articular injection of danshen (0.7 mL/day) for 5 weeks. In addition to attenuating the cartilage degeneration of OA in the rabbits, danshen decreased the expression and activity of matrix metalloproteinase 9 (MMP-9) and MMP-13, and increased the expression of their natural inhibitors: tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) and TIMP-2. Apoptosis in osteoarthritic cartilage tissues was attenuated by danshen, accompanied with increased expression of B cell lymphoma 2 (Bcl-2) and decreased levels of Bcl-2-associated X protein (Bax). Further, danshen inhibited the nuclear accumulation of nuclear factor kappa-B (NF-κB) p65 in osteoarthritic cartilage. The therapeutic effects of danshen in vivo were comparable to that of sodium hyaluronate, which is a drug used clinically for the treatment OA. In vitro, sodium nitroprusside (SNP) was used to stimulate apoptosis in primary rabbit chondrocytes. We found that the SNP-induced apoptosis was mitigated by danshen. BAY11-7028, an inhibitor of the NF-κB pathway, augmented danshen's anti-apoptotic effects in cells exposed to SNP. When these results are considered together, they indicate that danshen alleviates the cartilage injury in rabbit OA through inhibition of the NF-κB signaling pathway.

MAG-EPA reduces severity of DSS-induced colitis in rats.

PubMed

Morin, Caroline; Blier, Pierre U; Fortin, Samuel

2016-05-15

Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the intestinal mucosa of the large bowel. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines involved in UC pathogenesis. The aim of this study was to determine the preventive and therapeutic potential of eicosapentaenoic acid monoglyceride (MAG-EPA) in an in vivo rats model of UC induced by dextran sulfate sodium (DSS). DSS rats were untreated or treated per os with MAG-EPA. Morphological, histological, and biochemical analyses were performed following MAG-EPA administrations. Morphological and histological analyses revealed that MAG-EPA pretreatment (12 days pre-DSS) and treatment (6 days post-DSS) exhibited strong activity in reducing severity of disease in DSS rats. Following MAG-EPA administrations, tissue levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 were markedly lower compared with rats treated only with DSS. MAG-EPA per os administration decrease neutrophil infiltration in colon tissues, as depicted by myelohyperoxidase activity. Results also revealed a reduced activation of NF-κB pathways correlated with a decreased expression of COX-2 in colon homogenates derived from MAG-EPA-pretreated and treated rats. Tension measurements performed on colon tissues revealed that contractile responses to methacholine and relaxing effect induced by sodium nitroprusside were largely increased following MAG-EPA treatment. The combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in DSS rats. Copyright © 2016 the American Physiological Society.

Characterization of vascular complications in experimental model of fructose-induced metabolic syndrome.

PubMed

El-Bassossy, Hany M; Dsokey, Nora; Fahmy, Ahmed

2014-12-01

Vascular dysfunction is an important complication associated with metabolic syndrome (MS). Here we fully characterized vascular complications in a rat model of fructose-induced MS. MS was induced by adding fructose (10%) to drinking water to male Wistar rats of 6 weeks age. Blood pressure (BP) and isolated aorta responses phenylephrine (PE), KCl, acetylcholine (ACh), and sodium nitroprusside (SNP) were recorded after 6, 9, and 12 weeks of fructose administration. In addition, serum levels of glucose, insulin, uric acid, tumor necrosis factor α (TNFα), lipids, advanced glycation end products (AGEs), and arginase activity were determined. Furthermore, aortic reactive oxygen species (ROS) generation, hemeoxygenase-1 expression, and collagen deposition were examined. Fructose administration resulted in a significant hyperinslinemia after 6 weeks which continued for 12 weeks. It was also associated with a significant increase in BP after 6 weeks which was stable for 12 weeks. Aorta isolated from MS animals showed exaggerated contractility to PE and KCl and impaired relaxation to ACh compared with control after 6 weeks which were clearer at 12 weeks of fructose administration. In addition, MS animals showed significant increases in serum levels of lipids, uric acid, AGEs, TNFα, and arginase enzyme activity after 12 weeks of fructose administration. Furthermore, aortae isolated from MS animals were characterized by increased ROS generation and collagen deposition. In conclusion, adding fructose (10%) to drinking water produces a model of MS with vascular complications after 12 weeks that are characterized by insulin resistance, hypertension, disturbed vascular reactivity and structure, hyperuricemia, dyslipidemia, and low-grade inflammation.

Cytosolic labile zinc: a marker for apoptosis in the developing rat brain.

PubMed

Lee, Joo-Yong; Hwang, Jung Jin; Park, Mi-Ha; Koh, Jae-Young

2006-01-01

Cytosolic zinc accumulation was thought to occur specifically in neuronal death (necrosis) following acute injury. However, a recent study demonstrated that zinc accumulation also occurs in adult rat neurons undergoing apoptosis following target ablation, and in vitro experiments have shown that zinc accumulation may play a causal role in various forms of apoptosis. Here, we examined whether intraneuronal zinc accumulation occurs in central neurons undergoing apoptosis during development. Embryonic and newborn Sprague-Dawley rat brains were double-stained for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) detection of apoptosis and immunohistochemical detection of stage-specific neuronal markers, such as nestin, proliferating cell nuclear antigen (PCNA), TuJ1 and neuronal nuclear specific protein (NeuN). The results revealed that apoptotic cell death occurred in neurons of diverse stages (neural stem cells, and dividing, young and adult neurons) throughout the brain during the embryonic and early postnatal periods. Further staining of brain sections with acid fuchsin or zinc-specific fluorescent dyes showed that all of the apoptotic neurons were acidophilic and contained labile zinc in their cell bodies. Cytosolic zinc accumulation was also observed in cultured cortical neurons undergoing staurosporine- or sodium nitroprusside (SNP)-induced apoptosis. In contrast, zinc chelation with CaEDTA or N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) reduced SNP-induced apoptosis but not staurosporine-induced apoptosis, indicating that cytosolic zinc accumulation does not play a causal role in all forms of apoptosis. Finally, the specific cytosolic zinc accumulation may have a practical application as a relatively simple marker for neurons undergoing developmental apoptosis.

Thyroid status and nitric oxide in rat arterial vessels.

PubMed

McAllister, R M; Albarracin, I; Price, E M; Smith, T K; Turk, J R; Wyatt, K D

2005-04-01

Thyroid disease has profound effects on cardiovascular function. Hypo- and hyperthyroidism, for example, are associated with reduced and increased maximal endothelium-dependent vasodilation respectively. We therefore hypothesized that the capacity for vascular nitric oxide (NO) formation is decreased in hypothyroidism and increased in hyperthyroidism. To test this hypothesis, rats were made hypothyroid (HYPO) with propylthiouracil or hyperthyroid (HYPER) with triiodothyronine over 3-4 months. Compared with euthyroid control rats (EUT), HYPO exhibited blunted growth and lower citrate synthase activity in the soleus muscle; HYPER exhibited left ventricular hypertrophy and higher citrate synthase activity in the soleus muscle (P<0.05 for all effects). The capacity for NO formation was determined in aortic extracts by formation of [3H]L-citrulline from [3H]L-arginine, i.e. NO synthase (NOS) activity. Thyroid status modulated NOS activity (EUT, 36.8 +/- 5.5 fmol/h per mg protein; HYPO, 26.0 +/- 7.9; HYPER, 64.6 +/- 12.7; P<0.05, HYPER vs HYPO). Expression of endothelial and neural isoforms of NOS was modulated by thyroid status in a parallel fashion. Capacity for responding to NO was also determined via measuring cGMP concentration in aortae incubated with sodium nitroprusside. Stimulated cGMP formation was also modulated by thyroid status (EUT, 73.0 +/- 20.2 pmol/mg protein; HYPO, 152.4 +/- 48.7; HYPER, 10.4 +/- 2.6; P<0.05, HYPER vs HYPO). These data indicate that thyroid status alters capacities for both formation of and responding to NO. The former finding may contribute to previous findings concerning vascular function in thyroid disease states.

Impaired Expression of Uncoupling Protein 2 (UCP2) Causes Defective Post-ischemic Angiogenesis in Mice Deficient in AMP-activated Protein Kinase α Subunits

PubMed Central

Xu, Ming-Jiang; Song, Ping; Shirwany, Najeeb; Liang, Bin; Xing, Junjie; Viollet, Benoit; Wang, Xian; Zhu, Yi; Zou, Ming-Hui

2011-01-01

Objective The aim of the present study was to determine whether mitochondrial uncoupling protein (UCP)-2 is required for AMPK-dependent angiogenesis in ischemia in vivo. Methods and Results Angiogenesis was assayed by monitoring endothelial tube formation (a surrogate for angiogenesis) in human umbilical vein endothelial cells (HUVECs), isolated mouse aortic endothelial cells (MAECs), and pulmomary microvascular endothelial cells (PMECs), or in ischemic thigh adductor muscles from wild-type (WT) mice or mice deficient in either AMPKα1 or AMPKα2. AMPK inhibition with pharmacological inhibitor (compound C) or genetic means (transfection of AMPKα-specific siRNA) significantly lowered the tube formation in HUVECs. Consistently, compared with WT mice, tube formation in MAECs isolated from either AMPKα1−/− or AMPKα2−/− mice, which exhibited oxidative stress and reduced expression of UCP2, were significantly impaired. In addition, adenoviral overexpression of UCP2, but not adenoviruses encoding green florescence protein (GFP), normalized tube formation in MAECs from either AMPKα1−/− or AMPKα2−/− mice. Similarly, supplementation with sodium nitroprusside (SNP), a nitric oxide (NO) donor, restored tube formation. Furthermore, ischemia significantly increased angiogenesis, serine 1177 phosphorylation of endothelial NO synthase (eNOS), and UCP2 in ischemic thigh adductor muscles from WT mice, but not from either AMPKα1−/− or AMPKα2−/− mice. Conclusion We conclude that AMPK-dependent UCP2 expression in endothelial cells promotes angiogenesis in vivo. PMID:21597006

Nitric Oxide (NO) Mediates the Inhibition of Form-Deprivation Myopia by Atropine in Chicks.

PubMed

Carr, Brittany J; Stell, William K

2016-12-05

Myopia is the most common childhood refractive disorder. Atropine inhibits myopia progression, but its mechanism is unknown. Here, we show that myopia-prevention by atropine requires production of nitric oxide (NO). Form-deprivation myopia (FDM) was induced in week-old chicks by diffusers over the right eye (OD); the left eye (OS) remained ungoggled. On post-goggling days 1, 3, and 5, OD received intravitreally 20 µL of phosphate-buffered saline (vehicle), or vehicle plus: NO source: L-arginine (L-Arg, 60-6,000 nmol) or sodium nitroprusside (SNP, 10-1,000 nmol); atropine (240 nmol); NO inhibitors: L-NIO or L-NMMA (6 nmol); negative controls: D-Arg (10 µmol) or D-NMMA (6 nmol); or atropine plus L-NIO, L-NMMA, or D-NMMA; OS received vehicle. On day 6 post-goggling, refractive error, axial length, equatorial diameter, and wet weight were measured. Vehicle-injected goggled eyes developed significant FDM. This was inhibited by L-Arg (ED50 = 400 nmol) or SNP (ED50 = 20 nmol), but not D-Arg. Higher-dose SNP, but not L-Arg, was toxic to retina/RPE. Atropine inhibited FDM as expected; adding NOS-inhibitors (L-NIO, L-NMMA) to atropine inhibited this effect dose-dependently, but adding D-NMMA did not. Equatorial diameter, wet weight, and metrics of control eyes were not affected by any treatment. In summary, intraocular NO inhibits myopia dose-dependently and is obligatory for inhibition of myopia by atropine.

Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long-term effects of social isolation during adolescence.

PubMed

Cruz, Fábio C; Duarte, Josiane O; Leão, Rodrigo M; Hummel, Luiz F V; Planeta, Cleopatra S; Crestani, Carlos C

2016-01-01

It has been demonstrated that disruption of social bonds and perceived isolation (loneliness) are associated with an increased risk of cardiovascular morbidity and mortality. Adolescence is proposed as a period of vulnerability to stress. Nevertheless, the impact of chronic social stress during this ontogenic period in cardiovascular function is poorly understood. Therefore, the purpose of this study was to compare the impact in cardiovascular function of social isolation for 3 weeks in adolescent and adult male rats. Also, the long-term effects of social isolation during adolescence were investigated longitudinally. Social isolation reduced body weight in adolescent, but not in adult animals. Disruption of social bonds during adolescence increased arterial pressure without affecting heart rate and pulse pressure (PP). Nevertheless, social isolation in adulthood reduced systolic arterial pressure and increased diastolic arterial pressure, which in turn decreased PP without affecting mean arterial pressure. Cardiovascular changes in adolescents, but not adults, were followed by facilitation of both baroreflex sensitivity and vascular reactivity to the vasodilator agent acetylcholine. Vascular responsiveness to either the vasodilator agent sodium nitroprusside or the vasoconstrictor agent phenylephrine was not affected by social isolation. Except for the changes in body weight and baroreflex sensitivity, all alterations evoked by social isolation during adolescence were reversed in adulthood after moving animals from isolated to collective housing. These findings suggest a vulnerability of adolescents to the effects of chronic social isolation in cardiovascular function. However, results indicate minimal cardiovascular consequences in adulthood of disruption of social bonds during adolescence. © 2015 Wiley Periodicals, Inc.

A sensitive and rapid assay for 4-aminophenol in paracetamol drug and tablet formulation, by flow injection analysis with spectrophotometric detection.

PubMed

Bloomfield, M S

2002-12-06

4-Aminophenol (4AP) is the primary degradation product of paracetamol which is limited at a low level (50 ppm or 0.005% w/w) in the drug substance by the European, United States, British and German Pharmacopoeias, employing a manual colourimetric limit test. The 4AP limit is widened to 1000 ppm or 0.1% w/w for the tablet product monographs, which quote the use of a less sensitive automated HPLC method. The lower drug substance specification limit is applied to our products, (50 ppm, equivalent to 25 mug 4AP in a tablet containing 500-mg paracetamol) and the pharmacopoeial HPLC assay was not suitable at this low level due to matrix interference. For routine analysis a rapid, automated assay was required. This paper presents a highly sensitive, precise and automated method employing the technique of Flow Injection (FI) analysis to quantitatively assay low levels of this degradant. A solution of the drug substance, or an extract of the tablets, containing 4AP and paracetamol is injected into a solvent carrier stream and merged on-line with alkaline sodium nitroprusside reagent, to form a specific blue derivative which is detected spectrophotometrically at 710 nm. Standard HPLC equipment is used throughout. The procedure is fully quantitative and has been optimised for sensitivity and robustness using a multivariate experimental design (multi-level 'Central Composite' response surface) model. The method has been fully validated and is linear down to 0.01 mug ml(-1). The approach should be applicable to a range of paracetamol products.

Nanoparticle inhalation impairs endothelium-dependent vasodilation in subepicardial arterioles

PubMed Central

LeBlanc, AJ; Cumpston, JL; Chen, BT; Frazer, D; Castranova, V; Nurkiewicz, TR

2009-01-01

Exposure to fine particulate matter (PM, mean aerodynamic diameter ≤ 2.5 μm) has been shown to be a risk factor for cardiovascular disease mortality and may contribute to acute coronary events such as myocardial infarction (MI). There is sufficient reason to believe that smaller particles, such as nanoparticles, might be even more detrimental than larger-sized particles due to their increased surface area and higher pulmonary deposition. Our lab showed that nanoparticle inhalation impairs endothelium-dependent arteriolar vasodilation in skeletal muscle. However, it is not known if coronary microvascular endothelial function is affected in a similar manner. Rats were exposed to filtered air (control) or TiO2 nanoparticles (primary particle diameter, ~21 nm) via inhalation at concentrations that produced measured depositions (10 μg) relevant to ambient air pollution. Subepicardial arterioles (~150 μm in diameter) were isolated and responses to transmural pressure, flow-induced dilation (FID), acetylcholine, the Ca2+ ionophore A23187, and sodium nitroprusside (SNP) assessed. Myogenic responsiveness was preserved between groups. In addition, there was no difference in the vasodilation to SNP, signifying that smooth muscle sensitivity to nitric oxide (NO) is unaffected by nano-TiO2 exposure. However, inhalation of nano-TiO2 produced an increase in spontaneous tone in coronary arterioles and also impaired endothelium-dependent FID. In addition, ACh- and A23187-induced vasodilation was also blunted in arterioles after inhalation of nano-TiO2. Data showed that nanoparticle exposure significantly impairs endothelium-dependent vasodilation in subepicardial arterioles. Such disturbances in coronary microvascular function are consistent with the cardiac events associated with particle pollution exposure. PMID:20077232

Changes in vascular reactivity induced by acute hyperthyroidism in isolated rat aortae.

PubMed

Honda, H; Iwata, T; Mochizuki, T; Kogo, H

2000-06-01

Hyperthyroidism was induced by subcutaneous injections of L-thyroxine (T(4)) (500 mg/kg/day) for 3 days in order to study whether adrenergic and muscarinic receptor-mediated vascular responses alter at an early stage of the disease. T(4) treatment was sufficient to induce a significant degree of thyroid weight loss, tachycardia, cardiac hypertrophy, and an elevation in serum T(4) levels. The tension of aortic ring preparations isolated from rats was measured isometrically to investigate the influence of acute hyperthyroidism. The contractions induced by norepinephrine (NE) were significantly suppressed in aortic rings from rats treated with T(4) compared with control rats. N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthase (NOS), significantly enhanced NE-induced contraction in aortic rings from both control and T(4)-treated rats, and the enhancement was greater in rats treated with T(4) than control rats. The relaxations induced by either acetylcholine (ACh) or sodium nitroprusside (SNP) were also significantly enhanced by T(4) treatment. L-NOARG abolished the relaxation induced by ACh in aortic rings from both control and T(4)-treated rats. L-NOARG shifted SNP-induced relaxation curves of aortic rings from those of control rats to the left, but not with rats treated with T(4). T(4) treatment showed no influence on the amount of endothelial NOS (eNOS) protein. These results suggest that vascular responses alter at an early stage of hyperthyroidism and that it may be due to a modification in the NO system which is independent from the amount of eNOS protein.

Nitric oxide-mediated inhibition of taurocholate uptake involves S-nitrosylation of NTCP.

PubMed

Schonhoff, Christopher M; Ramasamy, Umadevi; Anwer, M Sawkat

2011-02-01

The sodium-taurocholate (TC) cotransporting polypeptide (NTCP) facilitates bile formation by mediating sinusoidal Na(+)-TC cotransport. During sepsis-induced cholestasis, there is a decrease in NTCP-dependent uptake of bile acids and an increase in nitric oxide (NO) levels in hepatocytes. In rat hepatocytes NO inhibits Na(+)-dependent uptake of taurocholate. The aim of this study was to extend these findings to human NTCP and to further investigate the mechanism by which NO inhibits TC uptake. Using a human hepatoma cell line stably expressing NTCP (HuH-NTCP), we performed experiments with the NO donors sodium nitroprusside and S-nitrosocysteine and demonstrated that NO inhibits TC uptake in these cells. Kinetic analyses revealed that NO significantly decreased the V(max) but not the K(m) of TC uptake by NTCP, indicating noncompetitive inhibition. NO decreased the amount of NTCP in the plasma membrane, providing a molecular mechanism for the noncompetitive inhibition of TC uptake. One way that NO can modify protein function is through a posttranslational modification known as S-nitrosylation: the binding of NO to cysteine thiols. Using a biotin switch technique we observed that NTCP is S-nitrosylated under conditions in which NO inhibits TC uptake. Moreover, dithiothreitol reversed NO-mediated inhibition of TC uptake and S-nitrosylation of NTCP, indicating that NO inhibits TC uptake via modification of cysteine thiols. In addition, NO treatment led to a decrease in Ntcp phosphorylation. Taken together these results indicate that the inhibition of TC uptake by NO involves S-nitrosylation of NTCP.

Influence of mitochondrion-toxic agents on the cardiovascular system.

PubMed

Finsterer, Josef; Ohnsorge, Peter

2013-12-01

Cardiovascular disease may be induced or worsened by mitochondrion-toxic agents. Mitochondrion-toxic agents may be classified as those with or without a clinical effect, those which induce cardiac disease only in humans or animals or both, as prescribed drugs, illicit drugs, exotoxins, or nutritiants, as those which affect the heart exclusively or also other organs, as those which are effective only in patients with a mitochondrial disorder or cardiac disease or also in healthy subjects, or as solid, liquid, or volatile agents. In humans, cardiotoxic agents due to mitochondrial dysfunction include anthracyclines (particularly doxorubicin), mitoxantrone, cyclophosphamide, cisplatin, fluorouracil, imatinib, bortezomib, trastuzumab, arsenic trioxide, cyclosporine-A, zidovudine, lamotrigine, glycosides, lidocain, isoproterenol, nitroprusside, pivalic acid, alcohol, cocaine, pesticides, cadmium, mycotoxins, cyanotoxins, meat meal, or carbon monoxide. Even more agents exhibit cardiac abnormalities due to mitochondrion-toxicity only in animals or tissue cultures. The mitochondrion-toxic effect results from impairment of the respiratory chain, the oxidative phosphorylation, the Krebs cycle, or the β-oxidation, from decrease of the mitochondrion-membrane potential, from increased oxidative stress, reduced anti-oxidative capacity, or from induction of apoptosis. Cardiac abnormalities induced via these mechanisms include cardiomyopathy, myocarditis, coronary heart disease, arrhythmias, heart failure, or Takotsubo syndrome. Discontinuation of the cardiotoxic agent results in complete recovery in the majority of the cases. Antioxidants and nutritiants may be of additional help. Particularly coenzyme-Q, riboflavin, vitamin-E, vitamin-C, L-carnitine, vitamin-D, thiamin, folic acid, omega-3 fatty acids, and D-ribose may alleviate mitochondrial cardiotoxic effects. Copyright © 2013 Elsevier Inc. All rights reserved.

A diminished aortic-cardiac reflex during hypotension in aerobically fit young men

NASA Technical Reports Server (NTRS)

Shi, X.; Crandall, C. G.; Potts, J. T.; Williamson, J. W.; Foresman, B. H.; Raven, P. B.

1993-01-01

We compared the aortic-cardiac baroreflex sensitivity in eight average fit (AF: VO2max = 44.7 +/- 1.3 ml.kg-1 x min-1) and seven high fit (HF: VO2max = 64.1 +/- 1.7 ml.min-1 x kg-1) healthy young men during hypotension elicited by steady state sodium nitroprusside (SN) infusion. During SN mean arterial pressure (MAP) was similarly decreased in AF (-12.6 +/- 1.0 mm Hg) and HF (-12.1 +/- 1.1 mm Hg). However, the increases in heart rate (HR) were less (P < 0.023) in HF (15 +/- 3 bpm) than AF (25 +/- 1 bpm). When sustained neck suction (NS, -22 +/- 1 torr in AF and -20 +/- 1 torr in HF, P > 0.05) was applied to counteract the decreased carotid sinus transmural pressure during SN, thereby isolating the aortic baroreceptors, the increased HR remained less (P < 0.021) in HF (8 +/- 2 bpm) than AF (16 +/- 2 bpm). During both SN infusion and SN+NS, the calculated gains (i.e., delta HR/delta MAP) were significantly greater in AF (2.1 +/- 0.3 and 1.3 +/- 0.2 bpm.mm Hg-1) than HF (1.2 +/- 0.2 and 0.6 +/- 0.2 bpm.mm Hg-1). However, the estimated carotid-cardiac baroreflex sensitivity (i.e., the gain difference between the stage SN and SN + NS) was not different between AF (0.7 +/- 0.2 bpm.mm Hg-1) and HF (0.6 +/- 0.1 bpm.mm Hg-1). These data indicated that the aortic-cardiac baroreflex sensitivity during hypotension was significantly diminished with endurance exercise training.

The role of nitric oxide in regulation of the cardiovascular system in reptiles.

PubMed

Skovgaard, Nini; Galli, Gina; Abe, Augusto; Taylor, Edwin W; Wang, Tobias

2005-10-01

The roles that nitric oxide (NO) plays in the cardiovascular system of reptiles are reviewed, with particular emphasis on its effects on central vascular blood flows in the systemic and pulmonary circulations. New data is presented that describes the effects on hemodynamic variables in varanid lizards of exogenously administered NO via the nitric oxide donor sodium nitroprusside (SNP) and inhibition of nitric oxide synthase (NOS) by l-nitroarginine methyl ester (l-NAME). Furthermore, preliminary data on the effects of SNP on hemodynamic variables in the tegu lizard are presented. The findings are compared with previously published data from our laboratory on three other species of reptiles: pythons (), rattlesnakes () and turtles (). These five species of reptiles possess different combinations of division of the heart and structural complexity of the lungs. Comparison of their responses to NO donors and NOS inhibitors may reveal whether the potential contribution of NO to vascular tone correlates with pulmonary complexity and/or with blood pressure. All existing studies on reptiles have clearly established a potential role for NO in regulating vascular tone in the systemic circulation and NO may be important for maintaining basal systemic vascular tone in varanid lizards, pythons and turtles, through a continuous release of NO. In contrast, the pulmonary circulation is less responsive to NO donors or NOS inhibitors, and it was only in pythons and varanid lizards that the lungs responded to SNP. Both species have a functionally separated heart, so it is possible that NO may exert a larger role in species with low pulmonary blood pressures, irrespective of lung complexity.

Promoting effects of chemical permeation enhancers on insulin permeation across TR146 cell model of buccal epithelium in vitro.

PubMed

Xue, Xiao-yan; Zhou, Ying; Chen, Ying-ying; Meng, Jing-ru; Jia, Min; Hou, Zheng; Bai, Hui; Mao, Xing-gang; Luo, Xiao-xing

2012-04-01

To find potential enhancers for facilitating the buccal delivery of insulin, a TR146 cell-culture model of buccal epithelium, cultured on commercially available insert plates, was used to evaluate the permeability-enhancing effects of several traditional and new types of chemical enhancers, including N-acetyl-L-cysteine (NAC), sodium deoxycholate (SDC), sodium nitroprusside (SNP), reduced glutathione (GSH), glutamine (Gln), chitosan (CS), L-arginine (Arg), 1-dodecylazacycloheptan-2-one (Azone), and soybean lecithin (SPC) (50 and 10 μg/mL respectively). Permeability studies were performed to determine the enhancing effects of these compounds on insulin permeation across the cell-culture model. The enhancing effects of the enhancers were assessed by calculating the apparent permeability coefficients and enhancement ratio. Cytotoxicity of the permeation enhancers at different concentrations was investigated by using the methylthiazolydiphenyl-tetrazolium bromide (MTT) assay. Results showed that 50 μg/mL of NAC, SDC, GSH, CS, Arg, Azone, SPC, SNP, and 10 μg/mL of SNP had a significant enhancing effect on promoting the transport of insulin across the TR146 cell model. MTT assays showed that 50 μg/mL of Gln, Azone, SDC, SNP, Arg, 10 μg/mL SDC, and Arg had obvious toxic effects on TR146 cells. Therefore, NAC, GSH, CS, SPC, and SNP appear to be safe, effective permeability enhancers that promote the transport of insulin across the TR146 cell-culture model of buccal epithelium and may be potential enhancers for buccal delivery of insulin with both low toxicity and high efficiency.

Brain purine metabolism and xanthine dehydrogenase/oxidase conversion in hyperammonemia are under control of NMDA receptors and nitric oxide.

PubMed

Kaminsky, Yury; Kosenko, Elena

2009-10-19

In hyperammonemia, a decrease in brain ATP can be a result of adenine nucleotide catabolism. Xanthine dehydrogenase (XD) and xanthine oxidase (XO) are the end steps in the purine catabolic pathway and directly involved in depletion of the adenylate pool in the cell. Besides, XD can easily be converted to XO to produce reactive oxygen species in the cell. In this study, the effects of acute ammonia intoxication in vivo on brain adenine nucleotide pool and xanthine and hypoxanthine, the end degradation products of adenine nucleotides, during the conversion of XD to XO were studied. Injection of rats with ammonium acetate was shown to lead to the dramatic decrease in the ATP level, adenine nucleotide pool size and adenylate energy charge and to the great increase in hypoxanthine and xanthine 11 min after the lethal dose indicating rapid degradation of adenylates. Conversion of XD to XO in hyperammonemic rat brain was evidenced by elevated XO/XD activity ratio. Injection of MK-801, a NMDA receptor blocker, prevented ammonia-induced catabolism of adenine nucleotides and conversion of XD to XO suggesting that in vivo these processes are mediated by activation of NMDA receptors. The in vitro dose-dependent effects of sodium nitroprusside, a NO donor, on XD and XO activities are indicative of the direct modification of the enzymes by nitric oxide. This is the first report evidencing the increase in brain xanthine and hypoxanthine levels and adenine nucleotide breakdown in acute ammonia intoxication and NMDA receptor-mediated prevention of these alterations.

Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells

PubMed Central

Eroglu, Emrah; Rost, Rene; Bischof, Helmut; Blass, Sandra; Schreilechner, Anna; Gottschalk, Benjamin; Depaoli, Maria R.; Klec, Christiane; Charoensin, Suphachai; Madreiter-Sokolowski, Corina T.; Ramadani, Jeta; Waldeck-Weiermair, Markus; Graier, Wolfgang F.; Malli, Roland

2017-01-01

Nitric Oxide (NO•) is a small radical, which mediates multiple important cellular functions in mammals, bacteria and plants. Despite the existence of a large number of methods for detecting NO• in vivo and in vitro, the real-time monitoring of NO• at the single-cell level is very challenging. The physiological or pathological effects of NO• are determined by the actual concentration and dwell time of this radical. Accordingly, methods that allow the single-cell detection of NO• are highly desirable. Recently, we expanded the pallet of NO• indicators by introducing single fluorescent protein-based genetically encoded nitric oxide (NO•) probes (geNOps) that directly respond to cellular NO• fluctuations and, hence, addresses this need. Here we demonstrate the usage of geNOps to assess intracellular NO• signals in response to two different chemical NO•-liberating molecules. Our results also confirm that freshly prepared 3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine (NOC-7) has a much higher potential to evoke change in intracellular NO• levels as compared with the inorganic NO• donor sodium nitroprusside (SNP). Furthermore, dual-color live-cell imaging using the green geNOps (G-geNOp) and the chemical Ca2+ indicator fura-2 was performed to visualize the tight regulation of Ca2+-dependent NO• formation in single endothelial cells. These representative experiments demonstrate that geNOps are suitable tools to investigate the real-time generation and degradation of single-cell NO• signals in diverse experimental setups. PMID:28362417

Minoxidil-associated anorexia in an infant with refractory hypertension.

PubMed

Vesoulis, Zachary A; Attarian, Stephanie J; Zeller, Brandy; Cole, Francis Sessions

2014-12-01

Minoxidil is a potent antihypertensive used as an adjunctive agent in refractory hypertension. It exerts an antihypertensive effect through two mechanisms: selective arterial vasodilation by activation of potassium channels in the vascular smooth muscle and stimulation of carotid and aortic baroreceptors, leading to downstream release of renin and norepinephrine. Although frequently cited in reviews of antihypertensive agents, limited data about the use of minoxidil in neonates are available. We describe an infant girl, born at 35 weeks of gestation, who was diagnosed with idiopathic hypertension after extensive diagnostic evaluation. Adequate blood pressure control was not achieved with captopril, amlodipine, and clonidine. Oliguria secondary to captopril and rapid-onset congestive heart failure due to persistent hypertension led to the introduction of intravenous agents labetalol and nitroprusside. Although adequate blood pressure control was achieved, attempts to transition back to oral agents were unsuccessful, prompting the use of minoxidil as an alternative agent. Although good blood pressure control was achieved, the infant's oral intake plummeted from 210 to 63 ml/kg/day. The anorexia quickly resolved after stopping minoxidil, and she was discharged home at 5 months of age receiving propranolol, amlodipine, and doxazosin. Use of the Naranjo adverse drug reaction probability scale indicated a definite relationship (score of 10) between the patient's development of anorexia and minoxidil therapy. To our knowledge, there have been no previous reports of minoxidil-associated anorexia in preterm or term infants. Clinicians should be aware that anorexia is a possible adverse effect of minoxidil in this patient population when initiating the drug in similar patients. © 2014 Pharmacotherapy Publications, Inc.

Nitric Oxide Exerts Basal and Insulin-Dependent Anorexigenic Actions in POMC Hypothalamic Neurons

PubMed Central

Wellhauser, Leigh; Chalmers, Jennifer A.

2016-01-01

The arcuate nucleus of the hypothalamus represents a key center for the control of appetite and feeding through the regulation of 2 key neuronal populations, notably agouti-related peptide/neuropeptide Y and proopimelanocortin (POMC)/cocaine- and amphetamine-regulated transcript neurons. Altered regulation of these neuronal networks, in particular the dysfunction of POMC neurons upon high-fat consumption, is a major pathogenic mechanism involved in the development of obesity and type 2 diabetes mellitus. Efforts are underway to preserve the integrity or enhance the functionality of POMC neurons in order to prevent or treat these metabolic diseases. Here, we report for the first time that the nitric oxide (NO−) donor, sodium nitroprusside (SNP) mediates anorexigenic actions in both hypothalamic tissue and hypothalamic-derived cell models by mediating the up-regulation of POMC levels. SNP increased POMC mRNA in a dose-dependent manner and enhanced α-melanocortin-secreting hormone production and secretion in mHypoA-POMC/GFP-2 cells. SNP also enhanced insulin-driven POMC expression likely by inhibiting the deacetylase activity of sirtuin 1. Furthermore, SNP enhanced insulin-dependent POMC expression, likely by reducing the transcriptional repression of Foxo1 on the POMC gene. Prolonged SNP exposure prevented the development of insulin resistance. Taken together, the NO− donor SNP enhances the anorexigenic potential of POMC neurons by promoting its transcriptional expression independent and in cooperation with insulin. Thus, increasing cellular NO− levels represents a hormone-independent method of promoting anorexigenic output from the existing POMC neuronal populations and may be advantageous in the fight against these prevalent disorders. PMID:26930171

Pharmacological vasodilation improves insulin-stimulated muscle protein anabolism but not glucose utilization in older adults.

PubMed

Timmerman, Kyle L; Lee, Jessica L; Fujita, Satoshi; Dhanani, Shaheen; Dreyer, Hans C; Fry, Christopher S; Drummond, Micah J; Sheffield-Moore, Melinda; Rasmussen, Blake B; Volpi, Elena

2010-11-01

Skeletal muscle protein metabolism is resistant to the anabolic action of insulin in healthy, nondiabetic older adults. This defect is associated with impaired insulin-induced vasodilation and mTORC1 signaling. We hypothesized that, in older subjects, pharmacological restoration of insulin-induced capillary recruitment would improve the response of muscle protein synthesis and anabolism to insulin. Twelve healthy, nondiabetic older subjects (71 ± 2 years) were randomized to two groups. Subjects were studied at baseline and during local infusion in one leg of insulin alone (Control) or insulin plus sodium nitroprusside (SNP) at variable rate to double leg blood flow. We measured leg blood flow by dye dilution; muscle microvascular perfusion with contrast enhanced ultrasound; Akt/mTORC1 signaling by Western blotting; and muscle protein synthesis, amino acid, and glucose kinetics using stable isotope methodologies. There were no baseline differences between groups. Blood flow, muscle perfusion, phenylalanine delivery to the leg, and intracellular availability of phenylalanine increased significantly (P < 0.05) in SNP only. Akt phosphorylation increased in both groups but increased more in SNP (P < 0.05). Muscle protein synthesis and net balance (nmol · min(-1) · 100 ml · leg(-1)) increased significantly (P < 0.05) in SNP (synthesis, 43 ± 6 to 129 ± 25; net balance, -16 ± 3 to 26 ± 12) but not in Control (synthesis, 41 ± 10 to 53 ± 8; net balance, -17 ± 3 to -2 ± 3). Pharmacological enhancement of muscle perfusion and amino acid availability during hyperinsulinemia improves the muscle protein anabolic effect of insulin in older adults.

Acute elevations in salt intake and reduced renal mass hypertension compromise arteriolar dilation in rat cremaster muscle.

PubMed

Frisbee, J C; Lombard, J H

1999-05-01

Alterations in arteriolar reactivity to dilator agonists were assessed in the skeletal muscle microcirculation of normotensive male Sprague-Dawley rats fed either high- (4% NaCl; HS) or low- (0. 4% NaCl; LS) salt diets and in reduced renal mass hypertensive rats (RRM-HT) on a high-salt diet for 3 days. An in situ cremaster muscle preparation was superfused with physiological salt solution, transilluminated, and viewed via television microscopy. A videomicrometer was used to measure changes in diameter of distal arterioles in response to increasing concentrations of acetylcholine (ACH), iloprost (ILO), cholera toxin (CT), forskolin (FOR), and sodium nitroprusside (SNP). Arteriolar dilation in response to ACH, ILO, and CT was significantly reduced in both HS and RRM-HT rats, while responses to FOR and SNP were decreased in RRM-HT rats only. The maximum dilation of the arterioles (determined during superfusion of the muscle with Ca2+-free solution containing 10(-4) M adenosine) was similar in the normotensive control animals on LS and HS diets, but was reduced in the RRM-HT rats, suggesting that early anatomic remodeling of the vessel wall may be occurring with RRM-HT. We conclude that arteriolar reactivity to endothelium-dependent and -independent vasodilator agonists is impaired as early as 3 days after the development of RRM hypertension or commencement of a high-salt diet in normotensive rats. Structural remodeling of the arteriolar wall, although becoming evident in the hypertensive rats, takes longer to develop than the impaired vasodilator reactivity. Copyright 1999 Academic Press.

Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release.

PubMed

Steinberg, H O; Brechtel, G; Johnson, A; Fineberg, N; Baron, A D

1994-09-01

The purpose of this study was to examine whether insulin's effect to vasodilate skeletal muscle vasculature is mediated by endothelium-derived nitric oxide (EDNO). N-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthase, was administered directly into the femoral artery of normal subjects at a dose of 16 mg/min and leg blood flow (LBF) was measured during an infusion of saline (NS) or during a euglycemic hyperinsulinemic clamp (HIC) designed to approximately double LBF. In response to the intrafemoral artery infusion of L-NMMA, LBF decreased from 0.296 +/- 0.032 to 0.235 +/- 0.022 liters/min during NS and from 0.479 +/- 0.118 to 0.266 +/- 0.052 liters/min during HIC, P < 0.03. The proportion of NO-dependent LBF during NS and HIC was approximately 20% and approximately 40%, respectively, P < 0.003 (NS vs. HIC). To elucidate whether insulin increases EDNO synthesis/release or EDNO action, vasodilative responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) or the endothelium-independent vasodilator sodium nitroprusside (SNP) were studied in normal subjects during either NS or HIC. LBF increments in response to intrafemoral artery infusions of MCh but not SNP were augmented during HIC versus NS, P < 0.03. In summary, insulin-mediated vasodilation is EDNO dependent. Insulin vasodilation of skeletal muscle vasculature most likely occurs via increasing EDNO synthesis/release. Thus, insulin appears to be a novel modulator of the EDNO system.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nally, J.V. Jr.; Clarke, H.S. Jr.; Grecos, G.P.

In an effort to improve on the noninvasive detection of renal artery stenosis, we investigated the effect of angiotensin converting enzyme inhibition on computer-assisted /sup 99m/Tc-diethylenetriaminepentaacetic acid (DTPA) renal flow studies in a canine model of two-kidney, one clip hypertension and compared these findings with clearances of inulin and p-aminohippuric acid in the stenotic and contralateral kidney before and after converting enzyme inhibition. The /sup 99m/Tc-DTPA renal flow study with the converting enzyme inhibitor captopril (1.5 mg/kg bolus with 1.5 mg/min infusion) showed an increased sensitivity in the detection of unilateral renal artery stenosis over the use of the /supmore » 99m/Tc-DTPA study alone. Captopril induced striking alterations that were most evident in the 15-minute /sup 99m/Tc-DTPA renal flow study, in which all nine curves exhibited severely blunted uptake and excretion of the radionuclide. These changes were reversed during a recovery study without converting enzyme inhibition and were not seen when blood pressure was lowered with nitroprusside to a level similar to that observed during converting enzyme inhibition. The changes shown by the /sup 99m/Tc-DTPA study during converting enzyme inhibition correlated with a decrease in the glomerular filtration rate of the stenotic kidney. Captopril infusion significantly decreased the glomerular filtration rate of the stenotic kidney (16.0 +/- 3.1 vs 11.0 +/- 2.5 mg/min, p less than 0.03) but not of the contralateral kidney (32.4 +/- 2.6 vs 28.4 +/- 2.8 mg/min).« less

Involvement of cytochrome epoxygenase metabolites in cutaneous postocclusive hyperemia in humans.

PubMed

Cracowski, Jean-Luc; Gaillard-Bigot, Florence; Cracowski, Claire; Sors, Claire; Roustit, Matthieu; Millet, Claire

2013-01-15

Several mediators contribute to postocclusive reactive hyperemia (PORH) of the skin, including sensory nerves and endothelium-derived hyperpolarizing factors. The main objective of our study was to investigate the specific contribution of epoxyeicosatrienoic acids in human skin PORH. Eight healthy volunteers were enrolled in two placebo-controlled experiments. In the first experiment we studied the separate and combined effects of 6.5 mM fluconazole, infused through microdialysis fibers, and lidocaine/prilocaine cream on skin PORH following 5 min arterial occlusion. In the second experiment we studied the separate and combined effects of 6.5 mM fluconazole and 10 mM N(G)-monomethyl-l-arginine (l-NMMA). Skin blood flux was recorded using two-dimensional laser speckle contrast imaging. Maximal cutaneous vascular conductance (CVC(max)) was obtained following 29 mM sodium nitroprusside perfusion. The PORH peak at the placebo site averaged 66 ± 11%CVC(max). Compared with the placebo site, the peak was significantly lower at the fluconazole (47 ± 10%CVC(max); P < 0.001), lidocaine (29 ± 10%CVC(max); P < 0.001), and fluconazole + lidocaine (30 ± 10%CVC(max); P < 0.001) sites. The effect of fluconazole on the area under the curve was more pronounced. In the second experiment, the PORH peak was significantly lower at the fluconazole site, but not at the l-NMMA or combination site, compared with the placebo site. In addition to sensory nerves cytochrome epoxygenase metabolites, putatively epoxyeicosatrienoic acids, play a major role in healthy skin PORH, their role being more important in the time course rather than the peak.

AV3V lesions reduce the pressor response to L-glutamate into the RVLM.

PubMed

Vieira, Alexandre Antonio; Colombari, Eduardo; De Luca, Laurival A; Colombari, Débora Simões de Almeida; Menani, José V

2006-05-01

Neurons from the rostral ventrolateral medulla (RVLM) directly activate sympathetic pre-ganglionic neurons in the spinal cord. Hypertensive responses and sympathetic activation produced by different stimuli are strongly affected by lesions of the preoptic periventricular tissue surrounding the anteroventral third ventricle (AV3V region). Therefore, in the present study, we investigated the effects of acute (1 day) and chronic (15 days) electrolytic lesions of the AV3V region on the pressor responses produced by injections of the excitatory amino acid L-glutamate into the RVLM of unanesthetized rats. Male Holtzman rats with sham or electrolytic AV3V lesions and a stainless steel cannula implanted into the RVLM were used. The pressor responses produced by injections of L-glutamate (1, 5 and 10 nmol/100 nl) into the RVLM were reduced 1 day (9 +/- 4, 39 +/- 6 and 37 +/- 4 mm Hg, respectively) and 15 days after AV3V lesions (13 +/- 6, 39 +/- 4 and 43 +/- 4 mm Hg, respectively, vs. sham lesions: 29 +/- 3, 50 +/- 2 and 58 +/- 3 mm Hg, respectively). Injections of L-glutamate into the RVLM in sham or AV3V-lesioned rats produced no significant change in the heart rate (HR). Baroreflex bradycardia and tachycardia produced by iv phenylephrine or sodium nitroprusside, respectively, and the pressor and bradycardic responses to chemoreflex activation with iv potassium cyanide were not modified by AV3V lesions. The results suggest that signals from the AV3V region are important for sympathetic activation induced by L-glutamate into the RVLM.

Characterization of N-methyl-D-aspartate-evoked taurine release in the developing and adult mouse hippocampus.

PubMed

Saransaari, P; Oja, S S

2003-01-01

Taurine is an inhibitory amino acid acting as an osmoregulator and neuroromodulator in the brain, with neuroprotective properties. The ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA) greatly potentiates taurine release from brain preparations in both normal and ischemic conditions, the effect being particularly marked in the developing hippocampus. We now characterized the regulation of NMDA-stimulated taurine release from hippocampal slices from adult (3-month-old) and developing (7-day-old) mouse using a superfusion system. The NMDA-stimulated taurine release was receptor-mediated in both adult and developing mouse hippocampus. In adults, only NO-generating compounds, sodium nitroprusside, S-nitroso-N-acetylpenicillamine and hydroxylamine reduced the release, as did also NO synthase inhibitors, 7-nitroindazole and nitroarginine, indicating that the release is mediated by the NO/cGMP pathway. On the other hand, the regulation of the NMDA-evoked taurine release proved to be somewhat complex in the immature hippocampus. It was not affected by the NOergic compounds, but enhanced by the protein kinase C activator 4 beta-phorbol 12-myristate 13-acetate and adenosine receptor A(1) agonists, N(6)-cyclohexyladenosine and R(-)N(6)-(2-phenylisopropyl)adenosine in a receptor-mediated manner. The activation of both ionotropic 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors and metabotropic glutamate group I receptors also enhanced the evoked release. The NMDA-receptor-stimulated taurine release could be a part of the neuroprotective properties of taurine, being important particularly under cell-damaging conditions in the developing hippocampus and hence preventing excitotoxicity.

Exercise restores coronary vascular function independent of myogenic tone or hyperglycemic status in db/db mice.

PubMed

Moien-Afshari, Farzad; Ghosh, Sanjoy; Elmi, Shahrzad; Khazaei, Majid; Rahman, Mohammad M; Sallam, Nada; Laher, Ismail

2008-10-01

Regulation of coronary function in diabetic hearts is an important component in preventing ischemic cardiac events but remains poorly studied. Exercise is recommended in the management of diabetes, but its effects on diabetic coronary function are relatively unknown. We investigated coronary artery myogenic tone and endothelial function, essential elements in maintaining vascular fluid dynamics in the myocardium. We hypothesized that exercise reduces pressure-induced myogenic constriction of coronary arteries while improving endothelial function in db/db mice, a model of type 2 diabetes. We used pressurized mouse coronary arteries isolated from hearts of control and db/db mice that were sedentary or exercised for 1 h/day on a motorized exercise-wheel system (set at 5.2 m/day, 5 days/wk). Exercise caused a approximately 10% weight loss in db/db mice and decreased whole body oxidative stress, as measured by plasma 8-isoprostane levels, but failed to improve hyperglycemia or plasma insulin levels. Exercise did not alter myogenic regulation of arterial diameter stimulated by increased transmural pressure, nor did it alter smooth muscle responses to U-46619 (a thromboxane agonist) or sodium nitroprusside (an endothelium-independent dilator). Moderate levels of exercise restored ACh-simulated, endothelium-dependent coronary artery vasodilation in db/db mice and increased expression of Mn SOD and decreased nitrotyrosine levels in hearts of db/db mice. We conclude that the vascular benefits of moderate levels of exercise were independent of changes in myogenic tone or hyperglycemic status and primarily involved increased nitric oxide bioavailability in the coronary microcirculation.

Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals.

PubMed

Maley, Matthew J; House, James R; Tipton, Michael J; Eglin, Clare M

2015-08-01

Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027-0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043-0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.

4-Isopropyl-2,6-bis(1-phenylethyl)aniline 1, an Analogue of KTH-13 Isolated from Cordyceps bassiana, Inhibits the NF-κB-Mediated Inflammatory Response

PubMed Central

Yang, Woo Seok; Ratan, Zubair Ahmed; Kim, Gihyeon; Lee, Yunmi; Kim, Mi-Yeon; Kim, Jong-Hoon; Cho, Jae Youl

2015-01-01

The Cordyceps species has been a good source of compounds with anticancer and anti-inflammatory activities. Recently, we reported a novel compound (4-isopropyl-2,6-bis(1-phenylethyl)phenol, KTH-13) with anticancer activity isolated from Cordyceps bassiana and created several derivatives to increase its pharmacological activity. In this study, we tested one of the KTH-013 derivatives, 4-isopropyl-2,6-bis(1-phenylethyl)aniline 1 (KTH-13-AD1), with regard to anti-inflammatory activity under macrophage-mediated inflammatory conditions. KTH-13-AD1 clearly suppressed the production of nitric oxide (NO) and reactive oxygen species (ROS) in lipopolysaccharide (LPS) and sodium nitroprusside- (SNP-) treated macrophage-like cells (RAW264.7 cells). Similarly, this compound also reduced mRNA expression of inducible NO synthase (iNOS) and tumor necrosis factor-α (TNF-α), as analyzed by RT-PCR and real-time PCR. Interestingly, KTH-13-AD1 strongly diminished NF-κB-mediated luciferase activities and nuclear translocation of NF-κB family proteins. In accordance, KTH-13-AD1 suppressed the upstream signaling pathway of NF-κB activation, including IκBα, IKKα/β, AKT, p85/PI3K, and Src in a time- and dose-dependent manner. The autophosphorylation of Src and NF-κB observed during the overexpression of Src was also suppressed by KTH-13-AD1. These results strongly suggest that KTH-13-AD1 has strong anti-inflammatory features mediated by suppression of the Src/NF-κB regulatory loop. PMID:26819495

Beneficial effect of a polyphenol-rich diet on cardiovascular risk: a randomised control trial.

PubMed

Noad, Rebecca L; Rooney, Ciara; McCall, Damian; Young, Ian S; McCance, David; McKinley, Michelle C; Woodside, Jayne V; McKeown, Pascal P

2016-09-01

There is previous epidemiological evidence that intake of polyphenol-rich foods has been associated with reduced cardiovascular disease risk. We aimed to investigate the effect of increasing dietary polyphenol intake on microvascular function in hypertensive participants. All participants completed a 4-week run-in phase, consuming <2 portions of fruit and vegetables (F&V) daily and avoiding berries and dark chocolate. Subjects were then randomised to continue with the low-polyphenol diet for 8 weeks or to consume a high-polyphenol diet of six portions F&V (including one portion of berries/day and 50 g of dark chocolate). Endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside) vasodilator responses were assessed by venous occlusion plethysmography. Compliance with the intervention was measured using food diaries and biochemical markers. Final analysis of the primary endpoint was conducted on 92 participants. Between-group comparison of change in maximum % response to ACh revealed a significant improvement in the high-polyphenol group (p=0.02). There was a significantly larger increase in vitamin C, carotenoids and epicatechin in the high-polyphenol group (between-group difference p<0.001; p<0.001; p=0.008, respectively). This study has shown that increasing the polyphenol content of the diet via consumption of F&V, berries and dark chocolate results in a significant improvement in an established marker of cardiovascular risk in hypertensive participants. NCT01319786. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Developmental changes in endothelium-dependent pulmonary vasodilatation in pigs.

PubMed Central

Liu, S. F.; Hislop, A. A.; Haworth, S. G.; Barnes, P. J.

1992-01-01

1. We compared in vitro endothelium-dependent vasorelaxant responses to acetylcholine (ACh) and the endothelium-independent vasodilator response to sodium nitroprusside (SNP) in prostaglandin F2 alpha (PGF2 alpha)-precontracted muscular pulmonary arteries (PA) from pigs aged 5 min to 2 h (neonatal), 3-10 days, 3-8 weeks and adults. 2. In the pulmonary artery (PA) rings from neonatal animals, the vasodilator response to ACh was negligible. However, responses to ACh were present in all PA rings from older animals, being greatest at 3-10 days and then decreasing with age (P less than 0.001, ANOVA). ACh (30 microM) induced a 1 +/- 1%, 92 +/- 9%, 62 +/- 5% and 51 +/- 6% reduction of the PGF2 alpha-generated tension in neonatal, 3-10 days, 3-8 weeks and adult groups, respectively. 3. The relaxant response to SNP was present in the PA rings from all age groups and increased with age (P less than 0.001, ANOVA). SNP (1 microM)-induced relaxation was 55 +/- 9%, 73 +/- 7%, 97 +/- 5% and 93 +/- 6% in neonatal, 3-10 days, 3-8 week and adult groups, respectively. 4. Removal of the vascular endothelium abolished the relaxant response to ACh but had no effect on the response to SNP in any groups. 5. NG-monomethyl-L-arginine (30 microM), a nitric oxide synthesis inhibitor, inhibited the response to ACh but not to SNP. The lipoxygenase inhibitor, nordihydroguaiaretic acid, had no significant effect on responses to ACh or SNP in any group.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 PMID:1393265

N-hydroxylamine is not an intermediate in the conversion of L-arginine to an activator of soluble guanylate cyclase in neuroblastoma N1E-115 cells.

PubMed Central

Pou, S; Pou, W S; Rosen, G M; el-Fakahany, E E

1991-01-01

This study evaluates the role of N-hydroxylamine (NH2OH) in activating soluble guanylate cyclase in the mouse neuroblastoma clone N1E-115. It has been proposed that NH2OH is a putative intermediate in the biochemical pathway for the generation of nitric oxide (NO)/endothelium-derived relaxing factor (EDRF) from L-arginine. NH2OH caused a time- and concentration-dependent increase in cyclic GMP formation in intact cells. This response was not dependent on Ca2+. In cytosol preparations the activation of guanylate cyclase by L-arginine was dose-dependent and required Ca2+ and NADPH. In contrast, NH2OH itself did not activate cytosolic guanylate cyclase but it inhibited the basal activity of this enzyme in a concentration-dependent manner. The formation of cyclic GMP in the cytosolic fractions in response to NH2OH required the addition of catalase and H2O2. On the other hand, catalase and/or H2O2 lead to a decrease in L-arginine-induced cyclic GMP formation. Furthermore, NH2OH inhibited L-arginine- and sodium nitroprusside-induced cyclic GMP formation in the cytosol. The inhibition of L-arginine-induced cyclic GMP formation in the cytosol by NH2OH was not reversed by the addition of superoxide dismutase. These data strongly suggest that NH2OH is not a putative intermediate in the metabolism of L-arginine to an activator of guanylate cyclase. PMID:1671745

Sensing of blood pressure increase by transient receptor potential vanilloid 1 receptors on baroreceptors.

PubMed

Sun, Hao; Li, De-Pei; Chen, Shao-Rui; Hittelman, Walter N; Pan, Hui-Lin

2009-12-01

The arterial baroreceptor is critically involved in the autonomic regulation of homoeostasis. The transient receptor potential vanilloid 1 (TRPV1) receptor is expressed on both somatic and visceral sensory neurons. Here, we examined the TRPV1 innervation of baroreceptive pathways and its functional significance in the baroreflex. Resiniferatoxin (RTX), an ultrapotent analog of capsaicin, was used to ablate TRPV1-expressing afferent neurons and fibers in adult rats. Immunofluorescence labeling revealed that TRPV1 immunoreactivity was present on nerve fibers and terminals in the adventitia of the ascending aorta and aortic arch, the nodose ganglion neurons, and afferent fibers in the solitary tract of the brainstem. RTX treatment eliminated TRPV1 immunoreactivities in the aorta, nodose ganglion, and solitary tract. Renal sympathetic nerve activity, blood pressure, and heart rate were recorded in anesthetized rats. The baroreflex was triggered by lowering and raising blood pressure through intravenous infusion of sodium nitroprusside and phenylephrine, respectively. Inhibition of sympathetic nerve activity and heart rate by the phenylephrine-induced increase in blood pressure was largely impaired in RTX-treated rats. The maximum gain of the baroreflex function was significantly lower in RTX-treated than vehicle-treated rats. Furthermore, blocking of TRPV1 receptors significantly blunted the baroreflex and decreased the maximum gain of baroreflex function in the high blood pressure range. Our findings provide important new information that TRPV1 is expressed along the entire baroreceptive afferent pathway. TRPV1 receptors expressed on baroreceptive nerve endings can function as mechanoreceptors to detect the increase in blood pressure and maintain the homoeostasis.

Sensing of Blood Pressure Increase by Transient Receptor Potential Vanilloid 1 Receptors on Baroreceptors

PubMed Central

Sun, Hao; Li, De-Pei; Chen, Shao-Rui; Hittelman, Walter N.

2009-01-01

The arterial baroreceptor is critically involved in the autonomic regulation of homoeostasis. The transient receptor potential vanilloid 1 (TRPV1) receptor is expressed on both somatic and visceral sensory neurons. Here, we examined the TRPV1 innervation of baroreceptive pathways and its functional significance in the baroreflex. Resiniferatoxin (RTX), an ultrapotent analog of capsaicin, was used to ablate TRPV1-expressing afferent neurons and fibers in adult rats. Immunofluorescence labeling revealed that TRPV1 immunoreactivity was present on nerve fibers and terminals in the adventitia of the ascending aorta and aortic arch, the nodose ganglion neurons, and afferent fibers in the solitary tract of the brainstem. RTX treatment eliminated TRPV1 immunoreactivities in the aorta, nodose ganglion, and solitary tract. Renal sympathetic nerve activity, blood pressure, and heart rate were recorded in anesthetized rats. The baroreflex was triggered by lowering and raising blood pressure through intravenous infusion of sodium nitroprusside and phenylephrine, respectively. Inhibition of sympathetic nerve activity and heart rate by the phenylephrine-induced increase in blood pressure was largely impaired in RTX-treated rats. The maximum gain of the baroreflex function was significantly lower in RTX-treated than vehicle-treated rats. Furthermore, blocking of TRPV1 receptors significantly blunted the baroreflex and decreased the maximum gain of baroreflex function in the high blood pressure range. Our findings provide important new information that TRPV1 is expressed along the entire baroreceptive afferent pathway. TRPV1 receptors expressed on baroreceptive nerve endings can function as mechanoreceptors to detect the increase in blood pressure and maintain the homoeostasis. PMID:19726694

The effects of nitric oxide-cGMP pathway stimulation on dopamine in the medial preoptic area and copulation in DHT-treated castrated male rats

PubMed Central

Sato, Satoru M.; Wersinger, Scott R.; Hull, Elaine M.

2007-01-01

Dopamine (DA) in the medial preoptic area (MPOA) provides important facilitative influence on male rat copulation. We have shown that the nitric oxide-cGMP (NO-cGMP) pathway modulates MPOA DA levels and copulation. We have also shown that systemic estradiol (E2) maintains neuronal NO synthase (nNOS) immunoreactivity in the MPOA of castrates, as well as relatively normal DA levels. This effect of E2 on nNOS probably accounts for at least some of the previously demonstrated behavioral facilitation by intra-MPOA E2 administration in castrates. Therefore, we hypothesized that stimulation of the MPOA NO-cGMP pathway in dihydrotestosterone (DHT)-treated castrates should restore DA levels and copulatory behaviors. Reverse-dialysis of a NO donor, sodium nitroprusside (SNP), increased extracellular DA in the MPOA of DHT-treated castrates and restored the ability to copulate to ejaculation in half of the animals. A cGMP analog, 8-Br-cGMP, also increased extracellular DA, though not as robustly, but did not restore copulatory ability. The effectiveness of the NO donor in restoring copulation and MPOA DA levels is consistent with our hypothesis. However, the lack of behavioral effects of 8-Br-cGMP, despite its increase in MPOA DA, suggests that NO may have additional mediators in the MPOA in the regulation of copulation. Furthermore, the suboptimal copulation seen in the NO donor-treated animals suggests the importance of extra-MPOA systems in the regulation of copulation. PMID:17467707

Myosin Va Plays a Role in Nitrergic Smooth Muscle Relaxation in Gastric Fundus and Corpora Cavernosa of Penis

PubMed Central

Carew, Josephine A.; Goyal, Raj K.; Sullivan, Maryrose P.

2014-01-01

The intracellular motor protein myosin Va is involved in nitrergic neurotransmission possibly by trafficking of neuronal nitric oxide synthase (nNOS) within the nerve terminals. In this study, we examined the role of myosin Va in the stomach and penis, proto-typical smooth muscle organs in which nitric oxide (NO) mediated relaxation is critical for function. We used confocal microscopy and co-immunoprecipitation of tissue from the gastric fundus (GF) and penile corpus cavernosum (CCP) to localize myosin Va with nNOS and demonstrate their molecular interaction. We utilized in vitro mechanical studies to test whether smooth muscle relaxations during nitrergic neuromuscular neurotransmission is altered in DBA (dilute, brown, non-agouti) mice which lack functional myosin Va. Myosin Va was localized in nNOS-positive nerve terminals and was co-immunoprecipitated with nNOS in both GF and CCP. In comparison to C57BL/6J wild type (WT) mice, electrical field stimulation (EFS) of precontracted smooth muscles of GF and CCP from DBA animals showed significant impairment of nitrergic relaxation. An NO donor, Sodium nitroprusside (SNP), caused comparable levels of relaxation in smooth muscles of WT and DBA mice. These normal postjunctional responses to SNP in DBA tissues suggest that impairment of smooth muscle relaxation resulted from inhibition of NO synthesis in prejunctional nerve terminals. Our results suggest that normal physiological processes of relaxation of gastric and cavernosal smooth muscles that facilitate food accommodation and penile erection, respectively, may be disrupted under conditions of myosin Va deficiency, resulting in complications like gastroparesis and erectile dysfunction. PMID:24516539

Arginase Inhibition Improves Microvascular Endothelial Function in Patients With Type 2 Diabetes Mellitus.

PubMed

Kövamees, Oskar; Shemyakin, Alexey; Checa, Antonio; Wheelock, Craig E; Lundberg, Jon O; Östenson, Claes-Göran; Pernow, John

2016-11-01

The development of microvascular complications in diabetes is a complex process in which endothelial dysfunction is important. Emerging evidence suggests that arginase is a key mediator of endothelial dysfunction in type 2 diabetes mellitus by reciprocally regulating nitric oxide bioavailability. The aim of this prospective intervention study was to test the hypothesis that arginase activity is increased and that arginase inhibition improves microvascular endothelial function in patients with type 2 diabetes and microvascular dysfunction. Microvascular endothelium-dependent and -independent dilatation was determined in patients with type 2 diabetes (n = 12) and healthy age-matched control subjects (n = 12) with laser Doppler flowmetry during iontophoretic application of acetylcholine and sodium nitroprusside, respectively, before and after administration of the arginase inhibitor N ω -hydroxy-nor-L-arginine (120 min). Plasma ratios of amino acids involved in arginase and nitric oxide synthase activities were determined. The laser Doppler flowmetry data were the primary outcome variable. Microvascular endothelium-dependent dilatation was impaired in subjects with type 2 diabetes (P < .05). After administration of N ω -hydroxy-nor-L-arginine, microvascular endothelial function improved significantly in patients with type 2 diabetes to the level observed in healthy controls. Endothelium-independent vasodilatation did not change significantly. Subjects with type 2 diabetes had higher levels of ornithine and higher ratios of ornithine/citrulline and ornithine/arginine (P < .05), suggesting increased arginase activity. Arginase inhibition improves microvascular endothelial function in patients with type 2 diabetes and microvascular dysfunction. Arginase inhibition may represent a novel therapeutic strategy to improve microvascular endothelial function in patients with type 2 diabetes.

Nitric Oxide-Induced Apoptosis of Human Dental Pulp Cells Is Mediated by the Mitochondria-Dependent Pathway

PubMed Central

Park, Min Young; Jeong, Yeon Jin; Kang, Gi Chang; Kim, Mi-Hwa; Kim, Sun Hun; Chung, Hyun-Ju

2014-01-01

Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory responses. NO is produced by nitric oxide synthase (NOS), and NOS is abundantly expressed in the human dental pulp cells (HDPCs). NO produced by NOS can be cytotoxic at higher concentrations to HDPCs. However, the mechanism by which this cytotoxic pathway is activated in cells exposed to NO is not known. The purpose of this study was to elucidate the NO-induced cytotoxic mechanism in HDPCs. Sodium nitroprusside (SNP), a NO donor, reduced the viability of HDPCs in a dose- and time-dependent manner. We investigated the in vitro effects of nitric oxide on apoptosis of cultured HDPCs. Cells showed typical apoptotic morphology after exposure to SNP. Besides, the number of Annexin V positive cells was increased among the SNP-treated HDPCs. SNP enhanced the production of reactive oxygen species (ROS), and N-acetylcysteine (NAC) ameliorated the decrement of cell viability induced by SNP. However, a soluble guanylate cyclase inhibitor (ODQ) did not inhibited the decrement of cell viability induced by SNP. SNP increased cytochrome c release from the mitochondria to the cytosol and the ratio of Bax/Bcl-2 expression levels. Moreover, SNP-treated HDPCs elevated activities of caspase-3 and caspase-9. While pretreatment with inhibitors of caspase (z-VAD-fmk, z-DEVD-fmk) reversed the NO-induced apoptosis of HDPCs. From these results, it can be suggested that NO induces apoptosis of HDPCs through the mitochondria-dependent pathway mediated by ROS and Bcl-2 family, but not by the cyclic GMP pathway. PMID:24634593

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kruszyna, H.; Kruszyna, R.; Hurst, J.

A series of compounds were synthesized from ruthenium trichloride, and their ip LD50s were determined in mice: pentamminenitrosylruthenium(II) chloride, 8.9; chloronitrobis(2,2'-dipyridyl)ruthenium(II), 55; dichlorobis(2,2'-dipyridyl)ruthenium(II) 63; ruthenium trichloride, 108; and potassium pentachloronitrosylruthenate(II), 127 mg/kg. The two bis-bipyridyl complexes produced death in convulsions within minutes, whereas the remaining compounds resulted in long, debilitating courses with death occuring in 4 to 7 d. When given in massive overdoses, however, the compounds with inorganic ligands also produced rapid convulsive death in mice, and when given iv to anesthetized cats, they produced respiratory arrest. The major toxic effects of all the complexes appeared to be duemore » to the metal and not to its associated ligands. Only complexes having a nitrosyl ligand specifically relaxed vascular smooth muscle. Potassium pentabromoiridate(III) also relaxed rabbit aortic strips that had been contracted by adrenergic argonists, but potassium pentachloroiridate(III) did not. None of the complexes was as active as nitroprusside in relaxing aortic strips or in decreasing arterial blood pressure in cats. No compound tested was as potent as cisplatin in antitumor activity. The pentamminenitrosylruthenium(II) complex also relaxed guinea pig ileum and frog rectus abdominum when these isolated muscles had been contracted by acetylcholine. It appears that these organoruthenium compounds may produce death in central respiratory arrest, as do the inorganic complexes when given iv or ip in massive overdoses. In minimllylethal doses, the complexes with inorganic ligands may affect a variety of contractile tissues, perhaps by a general mechanism involving Ca. These complexes are apt to be generally cytotoxic as well.« less

Iloprost improves ventricular function in the hypertrophic and functionally impaired right heart by direct stimulation.

PubMed

Holmboe, Sarah; Andersen, Asger; Vildbrad, Mads D; Nielsen, Jan M; Ringgaard, Steffen; Nielsen-Kudsk, Jens E

2013-12-01

Right heart function is an important predictor of morbidity and mortality in patients suffering from pulmonary arterial hypertension and congenital heart diseases. We investigated whether the prostacyclin analog iloprost has a direct inotropic effect in the pressure-overloaded hypertrophic and dysfunctional right ventricle (RV). Rats were randomized to monocrotaline injection (60 mg/kg; [Formula: see text]), pulmonary trunk banding (PTB; [Formula: see text]), or a sham operation ([Formula: see text]). RV function was evaluated with magnetic resonance imaging, echocardiography, and invasive pressure measurements at baseline, after intravenous administration of placebo, iloprost 10 ng/kg/min, or iloprost 100 ng/kg/min (Ilo100). Infusion of Ilo100 induced a [Formula: see text] ([Formula: see text]) increase in stroke volume in the sham group and a [Formula: see text] ([Formula: see text]) increase in the PTB group. RV [Formula: see text] was elevated by [Formula: see text] ([Formula: see text]) in the sham group and by [Formula: see text] ([Formula: see text]) in the PTB group. An elevation in cardiac output of [Formula: see text] ([Formula: see text]) and an [Formula: see text] ([Formula: see text]) increase in RV systolic pressure were found in the PTB group. Iloprost caused a decrease in mean arterial blood pressure (MAP) in all groups of animals. An equal reduction in MAP induced by the arterial vasodilator nitroprusside did not improve any of the measured parameters of RV function. We conclude that iloprost has inotropic properties directly improving ventricular function in the hypertrophic and dysfunctional right heart of the rat.

Nitric oxide protects murine embryonic liver cells (BNL CL.2) from cytotoxicity induced by glucose deprivation.

PubMed

Pae, H O; Kim, H G; Paik, Y S; Paik, S G; Kim, Y M; Oh, G S; Chung, H T

2000-03-01

We investigated the protective effects of nitric oxide on cell death of murine embryonic liver cells (BNL CL.2) after glucose deprivation. Endogenous nitric oxide production by BNL CL.2 cells was induced by 6 hr pretreatment with interferon-gamma and lipopolysaccharide. We used sodium nitroprusside and S-nitroso-L-glutathione as exogenous nitric oxide-generating compounds. All agents were used at doses that did not show direct cytotoxicity as measured by crystal violet staining assay. In the BNL CL.2 cells, the viability dropped very steeply after 24 hr incubation with glucose-free media. Endogenous nitric oxide produced by treatment of the cells with interferon-gamma and lipopolysaccharide protected the cells from glucose deprivation-induced cytotoxicity, but did not protect them in the presence of the nitric oxide synthesis inhibitor, N(G)-monomethyl-L-arginine. Exogenous nitric oxide protected the cells from glucose deprivation-induced cytotoxicity in a concentration-dependent manner. Cytoprotection by nitric oxide donors was abolished by the use of nitric oxide scavenger, 2-phenyl-4,4,5,5,-tetramethylimidazole, but not by the soluble guanosine cyclase inhibitor, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. In addition, cytoprotective effects comparable to endogenous or exogenous nitric oxide were not observed when the cells were incubated with dibutyl guanosine 3',5'-cyclic monophosphate. Based upon these results, we suggest that nitric oxide may enhance the cell survival of BNL CL.2 cells after glucose deprivation via a guanosine 3',5'-cyclic monophosphate-independent pathway.

Thimerosal blocks stimulated but not basal release of endothelium-derived relaxing factor (EDRF) in dog isolated coronary artery.

PubMed Central

Crack, P.; Cocks, T.

1992-01-01

1. The effect of an acetly-coA lysolecithin acyltransferase inhibitor, thimerosal, on the release of endothelium-derived relaxing factor (EDRF) was examined in the greyhound isolated coronary artery. 2. Thimerosal (1-10 microM) relaxed fully, ring segments of coronary artery which were contracted with the thromboxane A2-mimetic, U46619 (30 nM). The response was endothelium-dependent, slow in both onset and time to reach maximum. The maximum relaxation to the highest concentration of thimerosal (10 microM) was maintained for 10-20 min before the tissue slowly regained active force (1-2 h) to the same or higher level as that prior to the addition of thimerosal. At this time the endothelium-dependent relaxation responses to acetylcholine (ACh), substance P (SP), bradykinin (BK) and the calcium ionophores, ionomycin and A23187 were abolished. The endothelium-dependent contractions to the nitric oxide synthase inhibitors, NG-nitro-L-arginine (L-NNA; 10-100 microM) and NG-monomethyl-L-arginine (L-NMMA: 10-100 microM), however, were unaffected. 3. Thimerosal (10 microM) did not affect the relaxation curve to sodium nitroprusside (SNP) nor the contraction curve to the thromboxane A2-mimetic, U46619. 4. Both the relaxation response to thimerosal and the selective block of the relaxation responses to stimulated EDRF release were unaffected by either indomethacin (10 microM) or superoxide dismutase (150 u ml-1). 5. L-NNA (100 microM) significantly blocked the relaxation curves to thimerosal and A23187 but not that to SNP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1384915

Different contributions of platelet-activating factor and nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

PubMed

Pettorossi, V E; Grassi, S

2001-01-01

In rat brainstem slices, we investigated the differential role of nitric oxide (NO) and platelet-activating factor (PAF) in long-term potentiation (LTP) induced in the ventral portion of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferents. The NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and the PAF receptor antagonist ginkgolide B (BN-52021) were administered before and after induction of potentiation. The effect of carboxy-PTIO was to completely prevent LTP. By contrast, BN-52021 only reduced the amplitude of HFS potentiation, which could develop fully at the drug washout or decline to zero, becoming a short-term phenomenon, in the case of long-lasting PAF receptor block. Both drugs, when given after HFS, had no effect on the already established potentiation, but whilst BN-52021 showed an influence within 5 min of the LTP induction, carboxy-PTIO did not affect the response once HFS was delivered. Moreover, we showed that the NO donor, sodium nitroprusside, and methylcarbamyl PAF (mc-PAF) induced LTP which was associated with an increase in glutamate release as shown by reduction in the paired-pulse facilitation ratio. The mc-PAF LTP was prevented by the NO scavenger, while NO LTP was only reduced by BN-52021. We suggest that NO and PAF are implicated as retrograde messengers in two different phases of vestibular LTP: NO in the induction phase; and PAF in the full expression phase.

Vascular reactivity of rabbit isolated renal and femoral resistance arteries in renal wrap hypertension.

PubMed

Khammy, Makhala M; Angus, James A; Wright, Christine E

2016-02-15

In rabbits with cellophane renal wrap hypertension, hindquarter and total vascular resistance changes to pressor and depressor agents are amplified compared to those of normotensive rabbits. The aim of the present study was to evaluate the in vitro pharmacodynamics of hypertensive and normotensive rabbit small artery segments isolated from the renal and hindquarter vascular beds. Using wire myography, the full range (Emax) and sensitivity (EC50) to a range of agonists of segments of renal interlobar (≈ 600 µm i.d.), renal arcuate (≈ 250 µm i.d.) and deep femoral branch (≈ 250 µm i.d.) arteries were assessed under normalised conditions of passive tension. Interlobar arteries from hypertensive rabbits were more sensitive (EC50) than those from normotensive rabbits to noradrenaline (6-fold), methoxamine (3-fold) and angiotensin II (3-fold). Arcuate artery reactivity was largely unaffected by hypertension. Deep femoral arteries from hypertensive rabbits had enhanced sensitivity only to noradrenaline (2-fold) and methoxamine (4-fold). Sensitivity to relaxation by acetylcholine was unaffected by hypertension in all arteries. Deep femoral arteries from hypertensive rabbits were more sensitive to sodium nitroprusside than normotensive counterparts. Adenosine caused little relaxation in renal arteries, but full relaxation in deep femoral arteries, unaltered by hypertension. This study found substantial heterogeneity in the pharmacodynamic profile of vessels isolated from different vascular beds and between arterial segments within the kidney. These profiles were differentially affected by hypertension suggesting that hypertension per se is not a resultant of general vascular dysfunction. Copyright © 2016 Elsevier B.V. All rights reserved.

Association of elevated blood pressure and impaired vasorelaxation in experimental Sprague-Dawley rats fed with heated vegetable oil

PubMed Central

2010-01-01

Background Poor control of blood pressure leads to hypertension which is a major risk factor for development of cardiovascular disease. The present study aimed to explore possible mechanisms of elevation in blood pressure following consumption of heated vegetable oil. Methods Forty-two male Sprague-Dawley rats were equally divided into six groups: Group I (control) - normal rat chow, Group II - fresh soy oil, Group III - soy oil heated once, Group IV - soy oil heated twice, Group V - soy oil heated five times, Group VI - soy oil heated ten times. Blood pressure was measured at the baseline level and at a monthly interval for six months. Plasma nitric oxide, heme oxygenase and angiotensin-converting enzyme levels were measured prior to treatment, at month-three and month-six later. At the end of treatment, the rats were sacrificed and thoracic aortas were taken for measurement of vascular reactivity. Results Blood pressure increased significantly (p < 0.01) in the repeatedly heated oil groups compared to the control and fresh soy oil groups. Consumption of diet containing repeatedly heated oil resulted higher plasma angiotensin-converting enzyme level and lower nitric oxide content and heme oxygenase concentration. Reheated soy oil groups exhibited attenuated relaxation in response to acetylcholine or sodium nitroprusside, and greater contraction to phenylephrine. Conclusion As a result of consumption of repeatedly heated soy oil, an elevation in blood pressure was observed which may be due to the quantitative changes in endothelium dependent and independent factors including enzymes directly involved in the regulation of blood pressure. PMID:20573259

The promoter of the pepper pathogen-induced membrane protein gene CaPIMP1 mediates environmental stress responses in plants.

PubMed

Hong, Jeum Kyu; Hwang, Byung Kook

2009-01-01

The promoter of the pepper pathogen-induced membrane protein gene CaPIMP1 was analyzed by an Agrobacterium-mediated transient expression assay in tobacco leaves. Several stress-related cis-acting elements (GT-1, W-box and ABRE) are located within the CaPIMP1 promoter. In tobacco leaf tissues transiently transformed with a CaPIMP1 promoter-beta-glucuronidase (GUS) gene fusion, serially 5'-deleted CaPIMP1 promoters were differentially activated by Pseudomonas syringae pv. tabaci, ethylene, methyl jasmonate, abscisic acid, and nitric oxide. The -1,193 bp region of the CaPIMP1 gene promoter sequence exhibited full promoter activity. The -417- and -593 bp promoter regions were sufficient for GUS gene activation by ethylene and methyl jasmonate treatments, respectively. However, CaPIMP1 promoter sequences longer than -793 bp were required for promoter activation by abscisic acid and sodium nitroprusside treatments. CaPIMP1 expression was activated in pepper leaves by treatment with ethylene, methyl jasmonate, abscisic acid, beta-amino-n-butyric acid, NaCl, mechanical wounding, and low temperature, but not with salicylic acid. Overexpression of CaPIMP1 in Arabidopsis conferred hypersensitivity to mannitol, NaCl, and ABA during seed germination but not during seedling development. In contrast, transgenic plants overexpressing CaPIMP1 exhibited enhanced tolerance to oxidative stress induced by methyl viologen during germination and early seedling stages. These results suggest that CaPIMP1 expression may alter responsiveness to environmental stress, as well as to pathogen infection.

Endothelial dysfunction in rat mesenteric resistance artery after transient middle cerebral artery occlusion.

PubMed

Martinez-Revelles, Sonia; Jiménez-Altayó, Francesc; Caracuel, Laura; Pérez-Asensio, Fernando J; Planas, Anna M; Vila, Elisabet

2008-05-01

Stroke triggers a local and systemic inflammatory response leading to the production of cytokines that can influence blood vessel reactivity. In this study, we aimed to assess whether cerebral ischemia/reperfusion could affect vasoconstriction and vasodilatation on mesenteric resistance arteries (MRA) from Wistar Kyoto rats. The right middle cerebral artery was occluded (90 min) and reperfused (24 h). Sham-operated animals were used as controls. Plasma levels of interleukin (IL)-6 and IL-1beta were measured at 24 h. Vasoconstrictor and vasodilator responses were recorded in a wire myograph. Protein expression was determined by Western blot and immunofluorescence, and superoxide anion (O(2)(.)) production was evaluated by ethidium fluorescence. In MRA, ischemia/reperfusion increased plasma levels of IL-6, O2. production, protein expression of cyclooxygenase-2, and protein tyrosine nitrosylation, but it impaired acetylcholine (ACh) vasodilatation without modifying the vasodilatations to sodium nitroprusside or the contractions to phenylephrine and KCl. Superoxide dismutase (SOD) and indomethacin reversed the impairment of ACh relaxation induced by ischemia/reperfusion. However, N(omega)-nitro-l-arginine methyl ester affected similarly ACh-induced vasodilatations in MRA of ischemic and sham-operated rats. Protein expression of endothelial and inducible nitric-oxide synthase, copper/zinc SOD, manganese SOD, and extracellular SOD was similar in both groups of rats. Our results show MRA endothelial dysfunction 24 h after brain ischemia/reperfusion. Excessive production of O2. in MRA mediates endothelial dysfunction, and the increase in plasma cytokine levels after brain ischemia/reperfusion might be involved in this effect.

Antiatherogenic effects of S-nitroso-N-acetylcysteine in hypercholesterolemic LDL receptor knockout mice.

PubMed

Krieger, M H; Santos, K F R; Shishido, S M; Wanschel, A C B A; Estrela, H F G; Santos, L; De Oliveira, M G; Franchini, K G; Spadari-Bratfisch, R C; Laurindo, F R M

2006-02-01

The pathophysiology of the NO/NO synthase system and dysfunctional changes in the endothelium in the early phases of the atherogenic process are incompletely understood. In this study, we investigated the effects of the nitrosothiol NO donor S-nitroso-N-acetylcysteine (SNAC) in the early prevention of plaque development in the hypercholesterolemic LDLr-/- mice as well as the changes in endothelium-dependent relaxation and NO synthase expression. LDLr-/- mice were fed a 1.25% cholesterol-enriched diet for 15 days. Plasma cholesterol/triglyceride levels increased and this increase was accompanied by the development of aortic root lesions. Aortic vasorelaxation to acetylcholine was increased, although endothelium-independent relaxation in response to sodium nitroprusside did not change, which suggest stimulated NO release enhanced. This dysfunction was associated with enhanced aortic superoxide production and with increased levels of constitutive NOS isoform expression, particularly neuronal NOS. SNAC (S-nitroso-N-acetylcysteine) administration (0.51 micromol/kg/day i.p. for 15 days) decreased the extent of the plaque by 55% in hypercholesterolemic mice, but had no effects on vasomotor changes. It did, however, lead to a decrease in constitutive NOS expression. The SNAC induced only minor changes in plasma lipid profile. The present study has shown that, in early stages of plaque development in LDLr-/- mice, specific changes in NO/NO synthase system develop, that are characterized by increased endothelium-dependent vasorelaxation and increased constitutive NOS expression. Since the development of plaque and the indicator of endothelial cell dysfunction were prevented by SNAC, such treatment may constitute a novel strategy for the halting of progression of early plaque.

N-acetylcysteine improves coronary and peripheral vascular function.

PubMed

Andrews, N P; Prasad, A; Quyyumi, A A

2001-01-01

We investigated whether N-acetylcysteine (NAC), a reduced thiol that modulates redox state and forms adducts of nitric oxide (NO), improves endothelium-dependent vasomotion. Coronary atherosclerosis is associated with endothelial dysfunction and reduced NO activity. In 16 patients undergoing cardiac catheterization, seven with and nine without atherosclerosis, we assessed endothelium-dependent vasodilation with acetylcholine (ACH) and endothelium-independent vasodilation with nitroglycerin (NTG) and sodium nitroprusside (SNP) before and after intracoronary NAC. In 14 patients femoral vascular responses to ACH, NTG and SNP were measured before and after NAC. Intraarterial NAC did not change resting coronary or peripheral vascular tone. N-acetylcysteine potentiated ACH-mediated coronary vasodilation; coronary blood flow was 36 +/- 11% higher (p < 0.02), and epicardial diameter changed from -1.2 +/- 2% constriction to 4.7 +/- 2% dilation after NAC (p = 0.03). Acetylcholine-mediated femoral vasodilation was similarly potentiated by NAC (p = 0.001). Augmentation of the ACH response was similar in patients with or without atherosclerosis. N-acetylcysteine did not affect NTG-mediated vasodilation in either the femoral or coronary circulations and did not alter SNP responses in the femoral circulation. In contrast, coronary vasodilation with SNP was significantly greater after NAC (p < 0.05). Thiol supplementation with NAC improves human coronary and peripheral endothelium-dependent vasodilation. Nitroglycerin responses are not enhanced, but SNP-mediated responses are potentiated only in the coronary circulation. These NO-enhancing effects of thiols reflect the importance of the redox state in the control of vascular function and may be of therapeutic benefit in treating acute and chronic manifestations of atherosclerosis.

Antihypertensive mechanisms of chronic captopril or N-acetylcysteine treatment in L-NAME hypertensive rats.

PubMed

Zicha, Josef; Dobesová, Zdenka; Kunes, Jaroslav

2006-12-01

Hypertension due to chronic inhibition of NO synthase (NOS) by Nomega-nitro-L-arginine methyl ester (L-NAME) administration is characterized by both impaired NO-dependent vasodilation and enhanced sympathetic vasoconstriction. The aim of our study was to evaluate changes in the participation of major vasoactive systems in L-NAME-treated rats which were subjected to simultaneous antihypertensive (captopril) or antioxidant (N-acetylcysteine, NAC) treatment. Three-month-old Wistar males treated with L-NAME (60 mg/kg/day) for 5 weeks were compared to rats in which L-NAME treatment was combined with simultaneous chronic administration of captopril or NAC. Basal blood pressure (BP) and its acute responses to consecutive i.v. injections of captopril (10 mg/kg), pentolinium (5 mg/kg), L-NAME (30 mg/kg), tetraethylammonium (TEA, 16 mg/kg) and nitroprusside (NP, 20 microg/kg) were determined in conscious rats at the end of the study. The development of L-NAME hypertension was prevented by captopril treatment, whereas NAC treatment caused only a moderate BP reduction. Captopril treatment normalized the sympathetic BP component and significantly reduced residual BP (measured at full NP-induced vasodilation). In contrast, chronic NAC treatment did not modify the sympathetic BP component or residual BP, but significantly enhanced NO-dependent vasodilation. Neither captopril nor NAC treatment influenced the compensatory increase of TEA-sensitive vasodilation mediated by endothelium-derived hyperpolarizing factor in L-NAME-treated rats. Chronic captopril treatment prevented L-NAME hypertension by lowering of sympathetic tone, whereas chronic NAC treatment attenuated L-NAME hypertension by reduction in the vasodilator deficit due to enhanced NO-dependent vasodilation.

Nitrergic cardiovascular regulation in the African lungfish, Protopterus aethiopicus.

PubMed

Filogonio, Renato; Joyce, William; Wang, Tobias

2017-05-01

As a ubiquitous signaling molecule, nitric oxide (NO) exerts various important effects on the cardiovascular system and is involved in the regulation of vascular tone and myocardial metabolism in vertebrates. Lungfishes are closely related to tetrapods and provide an interesting possibility to understand the transition from water to land. Lungfishes are endowed with both systemic and pulmonary circulations, and their incompletely divided ventricle allows for blood to bypass either circuit. Lungfishes inhabit ephemeral waterbodies that may enforce prolonged aestivation during drought, throughout which nitric oxide synthase (NOS) expression is upregulated. To better understand the physiological relevance of NO on cardiovascular regulation in this transitory group, we measured vascular reactivity to muscarinic agonist acetylcholine, α- and β-adrenergic agonists (phenylephrine and isoproterenol, respectively), or the NO donor, sodium nitroprusside (SNP) on four vessel segments-efferent branchial arteries, gill artery, ductus arteriosus and pulmonary artery-from the African lungfish, Protopterus aethiopicus. In a simultaneous study, we measured oxygen consumption and twitch force in myocardial preparations in the presence and absence of an NOS inhibitor (asymmetric dimethylarginine; ADMA). Only the ductus arteriosus vasodilated in response to SNP. Isoproterenol caused vasodilation, whereas acetylcholine and phenylephrine vasoconstricted all vessel segments. NOS inhibition decreased myocardial force relative to oxygen consumption, indicating a lowered efficiency. We provide novel evidence that NO affects the vasculature of lungfish that may be derived from perivascular nitrergic nerves limited to the ductus arteriosus. Our data also suggests that NO exerts a tonic dampening of myocardial oxygen consumption which may be particularly important during aestivation. Copyright © 2017 Elsevier Inc. All rights reserved.

An animal model for the analysis of cochlear blood flow [corrected] disturbance and hearing threshold in vivo.

PubMed

Canis, Martin; Arpornchayanon, Warangkana; Messmer, Catalina; Suckfuell, Markus; Olzowy, Bernhard; Strieth, Sebastian

2010-02-01

Impairment of cochlear blood flow (CBF) is considered to be important in inner ear pathology. However, direct measurement of CBF is difficult and has not been investigated in combination with hearing function. Six guinea pigs were used to show feasibility of an animal model for the analysis of cochlear microcirculation by intravital microscopy in combination with investigation of the hearing threshold by brainstem response audiometry (ABR). By the application of sodium nitroprusside (SNP), CBF was increased over 30 min. Reproducibility of measurements was shown by retest measurements. Mean baseline velocity of CBF was 109 +/- 19 mum/s. Vessel diameters had a mean value of 9.4 +/- 2.7 mum. Mean hearing threshold was 19 +/- 6 dB. In response to SNP, CBF velocity increased significantly to 161 +/- 26 mum/s. Mean arterial pressure decreased significantly to 36 +/- 11 mmHg. After the end of the application, CBF velocity recovered to a minimum of 123 +/- 17 microm/s. Within the retest, CBF velocity significantly increased to a maximum of 160 +/- 31 microm/s. Second recovery of CBF velocity was 125 +/- 14 mum/s. Within the second retest, CBF increased significantly to 157 +/- 25 microm/s. ABR thresholds did not change significantly. The increase in blood flow velocity occurred in spite of substantial hypotension as induced by a vasodilator. This may explain the fact that ABR threshold remained unchanged reflecting a maintained blood supply in this part of the brain. This technique can be used to evaluate effects of treatments aimed at cochlear microcirculation in inner ear pathologies.

Acute retinal ischemia inhibits endothelium-dependent nitric oxide-mediated dilation of retinal arterioles via enhanced superoxide production.

PubMed

Hein, Travis W; Ren, Yi; Potts, Luke B; Yuan, Zhaoxu; Kuo, Enoch; Rosa, Robert H; Kuo, Lih

2012-01-03

Because retinal vascular disease is associated with ischemia and increased oxidative stress, the vasodilator function of retinal arterioles was examined after retinal ischemia induced by elevated intraocular pressure (IOP). The role of superoxide anions in the development of vascular dysfunction was assessed. IOP was increased and maintained at 80 to 90 mm Hg for 30, 60, or 90 minutes by infusing saline into the anterior chamber of a porcine eye. The fellow eye with normal IOP (10-20 mm Hg) served as control. In some pigs, superoxide dismutase mimetic TEMPOL (1 mM) or vehicle (saline) was injected intravitreally before IOP elevation. After enucleation, retinal arterioles were isolated and pressurized without flow for functional analysis by recording diameter changes using videomicroscopic techniques. Dihydroethidium (DHE) was used to detect superoxide production in isolated retinal arterioles. Isolated retinal arterioles developed stable basal tone and the vasodilations to endothelium-dependent nitric oxide (NO)-mediated agonists bradykinin and L-lactate were significantly reduced only by 90 minutes of ischemia. However, vasodilation to endothelium-independent NO donor sodium nitroprusside was unaffected after all time periods of ischemia. DHE staining showed that 90 minutes of ischemia significantly increased superoxide levels in retinal arterioles. Intravitreal injection of membrane-permeable radical scavenger but not vehicle before ischemia prevented elevation of vascular superoxide and preserved bradykinin-induced dilation. Endothelium-dependent NO-mediated dilation of retinal arterioles is impaired by 90 minutes of ischemia induced by elevated IOP. The inhibitory effect appears to be mediated by the alteration of NO signaling via vascular superoxide.

Comparison of skin microvascular reactivity with hemostatic markers of endothelial dysfunction and damage in type 2 diabetes

PubMed Central

Beer, Sandra; Feihl, François; Ruiz, Juan; Juhan-Vague, Irène; Aillaud, Marie-Françoise; Wetzel, Sandrine Golay; Liaudet, Lucas; Gaillard, Rolf C; Waeber, Bernard

2008-01-01

Aim: Patients with non-insulin-dependent diabetes mellitus (NIDDM) are at increased cardiovascular risk due to an accelerated atherosclerotic process. The present study aimed to compare skin microvascular function, pulse wave velocity (PWV), and a variety of hemostatic markers of endothelium injury [von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), tissue factor pathway inhibitor (TFPI), and the soluble form of thrombomodulin (s-TM)] in patients with NIDDM. Methods: 54 patients with NIDDM and 38 sex- and age-matched controls were studied. 27 diabetics had no overt micro- and/or macrovascular complications, while the remainder had either or both. The forearm skin blood flow was assessed by laser-Doppler imaging, which allowed the measurement of the response to iontophoretically applied acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation), as well as the reactive hyperemia triggered by the transient occlusion of the circulation. Results: Both endothelial and non-endothelial reactivity were significantly blunted in diabetics, regardless of the presence or the absence of vascular complications. Plasma vWF, TFPI and s-TM levels were significantly increased compared with controls only in patients exhibiting vascular complications. Concentrations of t-PA and PAI-1 were significantly increased in the two groups of diabetics versus controls. Conclusion: In NIDDM, both endothelium-dependent and -independent microvascular skin reactivity are impaired, whether or not underlying vascular complications exist. It also appears that microvascular endothelial dysfunction is not necessarily associated in NIDDM with increased circulating levels of hemostatic markers of endothelial damage known to reflect a hypercoagulable state. PMID:19337558

Naringin ameliorates endothelial dysfunction in fructose-fed rats.

PubMed

Malakul, Wachirawadee; Pengnet, Sirinat; Kumchoom, Chanon; Tunsophon, Sakara

2018-03-01

High fructose consumption is associated with metabolic disorders including hyperglycemia and dyslipidemia, in addition to endothelial dysfunction. Naringin, a flavonoid present in citrus fruit, has been reported to exhibit lipid lowering, antioxidant, and cardiovascular protective properties. Therefore, the present study investigated the effect of naringin on fructose-induced endothelial dysfunction in rats and its underlying mechanisms. Male Sprague-Dawley rats were given 10% fructose in drinking water for 12 weeks, whereas control rats were fed drinking water alone. Naringin (100 mg/kg) was orally administered to fructose fed rats during the last 4 weeks of the study. Following 12 weeks, blood samples were collected for measurement of blood glucose, serum lipid profile and total nitrate/nitrite (NOx). Vascular function was assessed by isometric tension recording. Aortic expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), and nitrotyrosine were evaluated by western blot analysis. Fructose feeding induced increased levels of blood glucose, total cholesterol, triglyceride, and low density lipoprotein. In rat aortae, fructose reduced acethycholine-induced vasorelaxation, without affecting sodium nitroprusside-induced vasorelaxation. Treatment of fructose-fed rats with naringin restored fructose-induced metabolic alterations and endothelial dysfunction. Fructose-fed rats also exhibited decreased serum NOx level, reduced eNOS and p-eNOS protein expression, and enhanced nitrotyrosine expression in aortae. These alterations were improved by naringin treatment. The results of the present study suggested that naringin treatment preserves endothelium-dependent relaxation in aortae from fructose fed rats. This effect is primarily mediated through an enhanced NO bioavailability via increased eNOS activity and decreased NO inactivated to peroxynitrite in aortae.

Piracetam improves mitochondrial dysfunction following oxidative stress

PubMed Central

Keil, Uta; Scherping, Isabel; Hauptmann, Susanne; Schuessel, Katin; Eckert, Anne; Müller, Walter E

2005-01-01

Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging. Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction following oxidative stress was investigated using PC12 cells and dissociated brain cells of animals treated with piracetam. Piracetam treatment at concentrations between 100 and 1000 μM improved mitochondrial membrane potential and ATP production of PC12 cells following oxidative stress induced by sodium nitroprusside (SNP) and serum deprivation. Under conditions of mild serum deprivation, piracetam (500 μM) induced a nearly complete recovery of mitochondrial membrane potential and ATP levels. Piracetam also reduced caspase 9 activity after SNP treatment. Piracetam treatment (100–500 mg kg−1 daily) of mice was also associated with improved mitochondrial function in dissociated brain cells. Significant improvement was mainly seen in aged animals and only less in young animals. Moreover, the same treatment reduced antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in aged mouse brain only, which are elevated as an adaptive response to the increased oxidative stress with aging. In conclusion, therapeutically relevant in vitro and in vivo concentrations of piracetam are able to improve mitochondrial dysfunction associated with oxidative stress and/or aging. Mitochondrial stabilization and protection might be an important mechanism to explain many of piracetam's beneficial effects in elderly patients. PMID:16284628

Nitric oxide released by Lactobacillus farciminis improves TNBS-induced colitis in rats.

PubMed

Lamine, F; Fioramonti, J; Bueno, L; Nepveu, F; Cauquil, E; Lobysheva, I; Eutamène, H; Théodorou, V

2004-01-01

Beneficial effects of lactobacilli have been reported in experimental colitis. On the other hand, despite the controversial role of nitric oxide (NO) in the inflammatory gut process, a protective action of exogenous NO in inflammation has been suggested. Consequently, this study aimed to determine the effect of (i) sodium nitroprusside (SNP), a NO donor and (ii) treatment with Lactobacillus farciminis, which produces NO in vitro, on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats and to evaluate the role of exogenous NO in this effect. Rats were divided into three groups receiving one of the following: (i) a continuous intracolonic (IC) infusion of SNP for 4 days, (ii) L. farciminis orally for 19 days, or (iii) saline. On day 1 and day 15, respectively, TNBS and saline were administrated IC, followed by a continuous IC infusion of saline or haemoglobin, a NO scavenger. At the end of treatments, the following parameters were evaluated: macroscopic damage of colonic mucosa, myeloperoxidase and nitric oxide synthase activities and colonic luminal NO production. In colitic rats, SNP and L. farciminis treatment significantly (P < 0.05) reduced macroscopic damage scores, myeloperoxidase and nitric oxide synthase activities compared to controls. Haemoglobin infusion abolished the anti-inflammatory effect of both NO donor treatments, but had no effect per se on colitis. NO released intraluminally by SNP infusion or by L. farciminis given orally improves TNBS-induced colitis in rats. These results indicate a protective role of NO donation in colonic inflammation and show for the first time a mechanism involving NO delivery by a bacterial strain reducing an experimental colitis.

Effects of nitric oxide and its congeners on sickle red blood cell deformability

PubMed Central

Belanger, Andrea M.; Keggi, Christian; Kanias, Tamir; Gladwin, Mark T.; Kim-Shapiro, Daniel B.

2015-01-01

BACKGROUND Sickle cell disease is characterized by hemoglobin (Hb) polymerization upon deoxygenation. Polymerization causes the sickle cells to become rigid and misshapen (sickling). Red blood cell (RBC) dehydration greatly increases polymerization. Cycles of sickling and unsickling cause an influx of calcium that leads to loss of potassium via the calcium-activated Gardos channel which dehydrates the cells leading to increased polymerization. In this study effects of NO and its congeners on RBC deformability were examined, focusing on sickle red blood cells. STUDY DESIGN AND METHODS Red blood cells from patients with sickle cell disease and from non-patients were exposed to various compounds that release NO or its congeners. Intracellular calcium was increased using a calcium ionophore or cycling of oxygen tension for sickle red blood cells. Deformability was measured by laser-assisted osmotic gradient ektacytometry. RESULTS Consistent with a previous report, sodium nitroprusside (SNP) was found to protect against calcium-induced loss of deformability in normal red blood cells, but (contrary to some previous reports) no effect of any NO donors was observed when calcium influx was not induced. Importantly, in studies of deoxygenation-induced dehydration of sickle RBCs, SNP resulted in substantial improvements in deformability (p=0.036) and hydration (p=0.024). Sodium nitrite showed similar trends. SNP was shown to have no effect on calcium influx, but reduced potassium efflux. CONCLUSION These data suggest SNP and perhaps certain nitrogen oxides (like nitrite) inhibit the Gardos channel and may be able to protect sickle cells from dehydration and thereby improve outcome in the disease. PMID:25912054

Elevated extracellular potassium prior to muscle contraction reduces onset and steady-state exercise hyperemia in humans.

PubMed

Terwoord, Janée D; Hearon, Christopher M; Luckasen, Gary J; Richards, Jennifer C; Joyner, Michael J; Dinenno, Frank A

2018-05-03

The increase in interstitial potassium (K + ) during muscle contractions is thought to be a vasodilatory signal that contributes to exercise hyperemia. To determine the role of extracellular K + in exercise hyperemia, we perfused skeletal muscle with K + prior to contractions such that the effect of any endogenously-released K + would be minimized. We tested the hypothesis that local, intra-arterial infusion of potassium chloride (KCl) at rest would impair vasodilation in response to subsequent rhythmic handgrip exercise in humans. In 11 young adults, we determined forearm blood flow (FBF; Doppler ultrasound) and vascular conductance (FVC; FBF/mean arterial pressure) during 4 minutes of rhythmic handgrip exercise at 10% of maximal voluntary contraction during 1) control conditions (CTRL), 2) infusion of KCl prior to the initiation of exercise, and 3) infusion of sodium nitroprusside (SNP) as a control vasodilator. Infusion of KCl or SNP elevated resting FVC similarly prior to the onset of exercise (CTRL: 39 {plus minus} 6 vs. KCl: 81 {plus minus} 12 and SNP: 82 {plus minus} 13 ml/min/100 mmHg; both P < 0.05 vs. CTRL). Infusion of KCl at rest diminished the hyperemic (Δ FBF) and vasodilatory (Δ FVC) response to subsequent exercise by 22 {plus minus} 5% and 30 {plus minus} 5%, respectively (both P < 0.05 vs. CTRL), whereas SNP did not affect the change in FBF (P = 0.74 vs. CTRL) or FVC (P = 0.61 vs. CTRL) from rest to steady-state exercise. These findings implicate the K + ion as an essential vasodilator substance contributing to exercise hyperemia in humans.

Acute exhaustive rowing exercise reduces skin microvascular dilator function in young adult rowing athletes.

PubMed

Stupin, Marko; Stupin, Ana; Rasic, Lidija; Cosic, Anita; Kolar, Luka; Seric, Vatroslav; Lenasi, Helena; Izakovic, Kresimir; Drenjancevic, Ines

2018-02-01

The effect of acute exhaustive exercise session on skin microvascular reactivity was assessed in professional rowers and sedentary subjects. A potential involvement of altered hemodynamic parameters and/or oxidative stress level in the regulation of skin microvascular blood flow by acute exercise were determined. Anthropometric, biochemical, and hemodynamic parameters were measured in 18 young healthy sedentary men and 20 professional rowers who underwent a single acute exercise session. Post-occlusive reactive hyperemia (PORH), endothelium-dependent acetylcholine (ACh), and endothelium-independent sodium nitroprusside (SNP) microvascular responses were assessed by laser Doppler flowmetry in skin microcirculation before and after acute exercise. Serum lipid peroxidation products and plasma antioxidant capacity were measured using spectrophotometry. At baseline, rowers had significantly lower diastolic blood pressure (DBP) and heart rate (HR), and higher stroke volume (SV), PORH, and endothelium-dependent vasodilation than sedentary. Acute exercise caused a significant increase in systolic blood pressure, DBP, HR, and SV and a decrease in total peripheral resistance in both groups. Acute exercise induced a significant impairment in PORH and ACh-induced response in rowers, but not in sedentary, whereas the SNP-induced vasodilation was not affected by acute exercise in any group. Antioxidant capacity significantly increased only in sedentary after acute exercise. Single acute exercise session impaired microvascular reactivity and endothelial function in rowers but not in sedentary, possibly due to (1) more rowing grades and higher exercise intensity achieved by rowers; (2) a higher increase in arterial pressure in rowers than in sedentary men; and (3) a lower antioxidant capacity in rowers.

Exercise training, vascular function, and functional capacity in middle-aged subjects.

PubMed

Maiorana, A; O'Driscoll, G; Dembo, L; Goodman, C; Taylor, R; Green, D

2001-12-01

The aim of this study was to investigate the effect of 8 wk of exercise training on functional capacity, muscular strength, body composition, and vascular function in sedentary but healthy subjects by using a randomized, crossover protocol. After familiarization sessions, 19 subjects aged 47 +/- 2 yr (mean +/- SE) undertook a randomized, crossover design study of the effect of 8 wk of supervised circuit training consisting of combined aerobic and resistance exercise. Peak oxygen uptake (.VO(2peak)), sum of 7 maximal voluntary contractions and the sum of 8 skinfolds and 5 segment girths were determined at entry, crossover, and 16 wk. Endothelium-dependent and -independent vascular function were determined by forearm strain-gauge plethysmography and intrabrachial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP) in 16 subjects. Training did not alter ACh or SNP responses. .VO(2peak), (28.6 +/- 1.1 to 32.6 +/- 1.3 mL.kg(-1).min(-1), P < 0.001), exercise test duration (17.4 +/- 1.1 to 22.1 +/- 1.2 min, P < 0.001), and muscular strength (465 +/- 27 to 535 +/- 27 kg, P < 0.001) significantly increased after the exercise program, whereas skinfolds decreased (144 +/- 10 vs 134 +/- 9 mm, P < 0.001). These results suggest that moderate intensity circuit training designed to minimize the involvement of the arms improves functional capacity, body composition, and strength in healthy, middle-aged subjects without significantly influencing upper limb vascular function. This finding contrasts with previous studies in subjects with type 2 diabetes and heart failure that employed an identical training program.

Resistance training controls arterial blood pressure in rats with L-NAME- induced hypertension.

PubMed

Araujo, Ayslan Jorge Santos de; Santos, Anne Carolline Veríssimo dos; Souza, Karine dos Santos; Aires, Marlúcia Bastos; Santana-Filho, Valter Joviniano; Fioretto, Emerson Ticona; Mota, Marcelo Mendonça; Santos, Márcio Roberto Viana

2013-04-01

Arterial hypertension is a multifactorial chronic condition caused by either congenital or acquired factors. To evaluate the effects of Resistance Training (RT) on arterial pressure, and on vascular reactivity and morphology, of L-NAME-treated hypertensive rats. Male Wistar rats (200 - 250 g) were allocated into Sedentary Normotensive (SN), Sedentary Hypertensive (SH) and Trained Hypertensive (TH) groups. Hypertension was induced by adding L-NAME (40 mg/Kg) to the drinking water for four weeks. Arterial pressure was evaluated before and after RT. RT was performed using 50% of 1RM, 3 sets of 10 repetitions, 3 times per week for four weeks. Vascular reactivity was measured in rat mesenteric artery rings by concentration-response curves to sodium nitroprusside (SNP); phenylephrine (PHE) was also used for histological and stereological analysis. Resistance training inhibited the increase in mean and diastolic arterial pressures. Significant reduction was observed in Rmax (maximal response) and pD2 (potency) of PHE between SH and TH groups. Arteries demonstrated normal intima, media and adventitia layers in all groups. Stereological analysis demonstrated no significant difference in luminal, tunica media, and total areas of arteries in the SH and TH groups when compared to the SN group. Wall-to-lumen ratio of SH arteries was significantly different compared to SN arteries (p<0.05) but there was no difference when compared to TH arteries. RT was able to prevent an increase in blood pressure under the conditions in this study. This appears to involve a vasoconstrictor regulation mechanism and maintenance of luminal diameter in L-NAME induced hypertensive rats.

Control of resin production in Araucaria angustifolia, an ancient South American conifer.

PubMed

Perotti, J C; da Silva Rodrigues-Corrêa, K C; Fett-Neto, A G

2015-07-01

Araucaria angustifolia is an ancient slow-growing conifer that characterises parts of the Southern Atlantic Forest biome, currently listed as a critically endangered species. The species also produces bark resin, although the factors controlling its resinosis are largely unknown. To better understand this defence-related process, we examined the resin exudation response of A. angustifolia upon treatment with well-known chemical stimulators used in fast-growing conifers producing both bark and wood resin, such as Pinus elliottii. The initial hypothesis was that A. angustifolia would display significant differences in the regulation of resinosis. The effect of Ethrel(®) (ET - ethylene precursor), salicylic acid (SA), jasmonic acid (JA), sulphuric acid (SuA) and sodium nitroprusside (SNP - nitric oxide donor) on resin yield and composition in young plants of A. angustifolia was examined. In at least one of the concentrations tested, and frequently in more than one, an aqueous glycerol solution applied on fresh wound sites of the stem with one or more of the adjuvants examined promoted an increase in resin yield, as well as monoterpene concentration (α-pinene, β-pinene, camphene and limonene). Higher yields and longer exudation periods were observed with JA and ET, another feature shared with Pinus resinosis. The results suggest that resinosis control is similar in Araucaria and Pinus. In addition, A. angustifolia resin may be a relevant source of valuable terpene chemicals, whose production may be increased by using stimulating pastes containing the identified adjuvants. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Augmentation of systemic blood pressure during spinal cord ischemia to prevent postoperative paraplegia after aortic surgery in a rabbit model.

PubMed

Izumi, So; Okada, Kenji; Hasegawa, Tomomi; Omura, Atsushi; Munakata, Hiroshi; Matsumori, Masamichi; Okita, Yutaka

2010-05-01

Paraplegia from spinal cord ischemia remains an unresolved complication in thoracoabdominal aortic surgery, with high morbidity and mortality. This study investigated postoperative effects of systemic blood pressure augmentation during ischemia. Spinal cord ischemia was induced in rabbits by infrarenal aortic occlusion for 15 minutes with infused phenylephrine (high blood pressure group, n = 8) or nitroprusside (low blood pressure group, n = 8) or without vasoactive agent (control, n = 8). Spinal cord blood flow, transcranial motor evoked potentials, neurologic outcome, and motor neuron cell damage (apoptosis, necrosis, superoxide generation, myeloperoxidase activity) were evaluated. Mean arterial pressures during ischemia were controlled at 121.9 +/- 2.8, 50.8 +/- 4.3, and 82.3 +/- 10.7 mm Hg in high blood pressure, low blood pressure, and control groups, respectively. In high blood pressure group, high spinal cord blood flow (P < .01), fast recovery of transcranial motor evoked potentials (P < .01), and high neurologic score (P < .05) were observed after ischemia relative to low blood pressure and control groups. At 48 hours after ischemia, there were significantly more viable neurons, fewer terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive neurons, and less alpha-fodrin expression in high blood pressure group than low blood pressure and control groups. Superoxide generation and myeloperoxidase activity at 3 hours after ischemia were suppressed in high blood pressure group relative to low blood pressure group. Augmentation of systemic blood pressure during spinal cord ischemia can reduce ischemic insult and postoperative neurologic adverse events. 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Nitric oxide alleviates oxidative damage induced by enhanced ultraviolet-B radiation in cyanobacterium.

PubMed

Xue, Lingui; Li, Shiweng; Sheng, Hongmei; Feng, Huyuan; Xu, Shijian; An, Lizhe

2007-10-01

To study the role of nitric oxide (NO) on enhanced ultraviolet-B (UV-B) radiation (280-320 nm)-induced damage of Cyanobacterium, the growth, pigment content, and antioxidative activity of Spirulina platensis-794 cells were investigated under enhanced UV-B radiation and under different chemical treatments with or without UV-B radiation for 6 h. The changes in chlorophyll-a, malondialdehyde content, and biomass confirmed that 0.5 mM: sodium nitroprusside (SNP), a donor of nitric oxide (NO), could markedly alleviate the damage caused by enhanced UV-B. Specifically, the biomass and the chlorophyll-a content in S. platensis-794 cells decreased 40% and 42%, respectively under enhanced UV-B stress alone, but they only decreased 10% and 18% in the cells treated with UV-B irradiation and 0.5 mM: SNP. Further experiments suggested that NO treatment significantly increased the activities of superoxide dismutase (SOD) and catalase (CAT), and decreased the accumulation of O (2)(-) in enhanced UV-B-irradiated cells. SOD and CAT activity increased 0.95- and 6.73-fold, respectively. The accumulation of reduced glutathione (GSH) increased during treatment with 0.5 mM: SNP in normal S. platensis cells, but SNP treatment could inhibit the increase of GSH in enhanced UV-B-stressed S. platensis cells. Thus, these results suggest that NO can strongly alleviate oxidative damage caused by UV-B stress by increasing the activities of SOD, peroxidase, CAT, and the accumulation of GSH, and by eliminating O (2)(-) in S. platensis-794 cells. In addition, the difference of NO origin between plants and cyanobacteria are discussed.

Hydrogen sulfide enhances nitric oxide-induced tolerance of hypoxia in maize (Zea mays L.).

PubMed

Peng, Renyi; Bian, Zhiyuan; Zhou, Lina; Cheng, Wei; Hai, Na; Yang, Changquan; Yang, Tao; Wang, Xinyu; Wang, Chongying

2016-11-01

Our data present H 2 S in a new role, serving as a multi-faceted transducer to different response mechanisms during NO-induced acquisition of tolerance to flooding-induced hypoxia in maize seedling roots. Nitric oxide (NO), serving as a secondary messenger, modulates physiological processes in plants. Recently, hydrogen sulfide (H 2 S) has been demonstrated to have similar signaling functions. This study focused on the effects of treatment with H 2 S on NO-induced hypoxia tolerance in maize seedlings. The results showed that treatment with the NO donor sodium nitroprusside (SNP) enhanced survival rate of submerged maize roots through induced accumulation of endogenous H 2 S. The induced H 2 S then enhanced endogenous Ca 2+ levels as well as the Ca 2+ -dependent activity of alcohol dehydrogenase (ADH), improving the capacity for antioxidant defense and, ultimately, the hypoxia tolerance in maize seedlings. In addition, NO induced the activities of key enzymes in H 2 S biosynthesis, such as L-cysteine desulfhydrases (L-CDs), O-acetyl-L-serine (thiol)lyase (OAS-TL), and β-Cyanoalanine Synthase (CAS). SNP-induced hypoxia tolerance was enhanced by the application of NaHS, but was eliminated by the H 2 S-synthesis inhibitor hydroxylamine (HA) and the H 2 S-scavenger hypotaurine (HT). H 2 S concurrently enhanced the transcriptional levels of relative hypoxia-induced genes. Together, our findings indicated that H 2 S serves as a multi-faceted transducer that enhances the nitric oxide-induced hypoxia tolerance in maize (Zea mays L.).

[Function of glutamate in pattern-gene-rating network is modified by nitric oxide NO].

PubMed

D'iakonova, T L; D'iakonova, V E

2007-03-01

In previous study on the terrestrial snail Helix pomatia, it has been shown that responsiveness of certain neurons to glutamate is controlled by NO; specifically, the donors of NO produced transformation of inhibitory responses to excitatory ones. Here, we extend this study to buccal neurons related to feeding behavior of the pond snail L. stagnalis. Glutamate is known to operate in the standard three-phase feeding pattern as a phase transmitter which mediates the effects of the second phase interneuron N2v. In isolated CNS, we recorded motor neuron B4 that was inhibited during firing of glutamatergic N2v, but expressed excitatory glutamate receptors as well. In some preparations (n = 17), bath application of 0.1 mM glutamate resulted in profound hyperpolarization of, and cessation of synaptic inputs to, the B4. Following treatment for 10-15 min with the NO donor sodium nitroprusside (n = 9), glutamate effect on B4 became excitatory, and a peculiar, sustained two-phase rhythmic activity of the pattern-generating network appeared. In other non-treated preparations (n = 12), 0.1 mM glutamate produced depolarization and excitation of B4, supplemented, in 8 cases, with emergence of the above mentioned two-phase rhythmic activity. Pretreatment for 10-20 min with the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (n = 7) abolished these effects of glutamate. Our results suggest that 1) glutamate role in buccal rhythm generation depends on NO level, and 2) this mechanism is involved in modification of the feeding behavior in Lymnaea.

In Vivo Cannabidiol Treatment Improves Endothelium-Dependent Vasorelaxation in Mesenteric Arteries of Zucker Diabetic Fatty Rats

PubMed Central

Wheal, Amanda J.; Jadoon, Khalid; Randall, Michael D.; O’Sullivan, Saoirse E.

2017-01-01

Background and purpose: We have shown that in vitro treatment with cannabidiol (CBD, 2 h) enhances endothelial function in arteries from Zucker diabetic fatty (ZDF) rats, partly due to a cyclooxygenase (COX)-mediated mechanism. The aim of the present study was to determine whether treatment with CBD in vivo would also enhance endothelial function. Experimental approach: Male ZDF rats, or ZDF Lean rats, were treated for 7 days (daily i.p. injection) with either 10mg/kg CBD or vehicle (n = 6 per group). Sections of mesenteric resistance arteries, femoral arteries and thoracic aortae were mounted on a wire myograph, and cumulative concentration-response curves to endothelium-dependent (acetylcholine, ACh, 1 nM–100 μM) or endothelium-independent (sodium nitroprusside, SNP, 1 nM–100 μM) agents were constructed. Multiplex analysis was used to measure serum metabolic and cardiovascular biomarkers. Key results: Vasorelaxation to ACh was significantly enhanced in mesenteric arteries from CBD-treated ZDF rats, but not ZDF Lean rats. The enhanced vasorelaxation in ZDF mesenteric arteries was no longer observed after COX inhibition using indomethacin or nitric oxide (NO) inhibition using L-NAME. Increased levels of serum c-peptide, insulin and intracellular adhesion molecule-1 observed in the ZDF compared to ZDF Lean rats were no longer significant after 7 days CBD treatment. Conclusion and implications: Short-term in vivo treatment with CBD improves ex vivo endothelium-dependent vasorelaxation in mesenteric arteries from ZDF rats due to COX- or NO-mediated mechanisms, and leads to improvements in serum biomarkers. PMID:28572770

Prominent expression of phosphodiesterase 5 in striated muscle of the rat urethra and levator ani.

PubMed

Lin, Guiting; Huang, Yun-Ching; Wang, Guifang; Lue, Tom F; Lin, Ching-Shwun

2010-08-01

We investigated phosphodiesterase 5 distribution and activity in the urethra. Rat tissues were examined for phosphodiesterase 5 and alpha-smooth muscle actin expression. Urethral phosphodiesterase 5 activity was examined by tissue bath in the presence of sildenafil (Pfizer, New York, New York). Anti-alpha-smooth muscle actin antibody (Abcam) stained all known smooth muscles in all tested tissues and revealed a few smooth muscle fibers in the levator ani muscle. Anti-phosphodiesterase 5 antibody (Abcam) stained smooth muscle in the penis and bladder but not striated leg muscle. However, it stained predominantly striated muscle in the urethra and the levator ani muscle. In the urethra the amount of phosphodiesterase 5 in striated muscle was 6 times that in smooth muscle. In urethral striated muscle phosphodiesterase 5 expression was localized to Z-band striations. Smooth and striated muscle intermingling was clearly visible on the inner and outer rims of the circularly arranged striated muscle layer. Relaxation of precontracted urethral tissues by sodium nitroprusside (Sigma-Aldrich) was enhanced by sildenafil, indicating phosphodiesterase 5 activity, which was primarily located in the striated muscle according to phosphodiesterase 5 staining. Despite its presumed smooth muscle specificity phosphodiesterase 5 was predominantly expressed in the striated muscle of the urethra and in the levator ani muscle. Results are consistent with earlier studies in which these striated muscles were developmentally related to smooth muscle. They also suggest that these striated muscles are possibly regulated by phosphodiesterase 5. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Acute and chronic effects of flavanol-rich cocoa on vascular function in subjects with coronary artery disease: a randomized double-blind placebo-controlled study.

PubMed

Farouque, H M Omar; Leung, Michael; Hope, Sarah A; Baldi, Mauro; Schechter, Clyde; Cameron, James D; Meredith, Ian T

2006-07-01

Evidence suggests that flavonoid-containing diets reduce cardiovascular risk, but the mechanisms responsible are unclear. In the present study, we sought to determine the effect of flavanol-rich cocoa on vascular function in individuals with CAD (coronary artery disease). Forty subjects (61+/-8 years; 30 male) with CAD were recruited to a 6-week randomized double-blind placebo-controlled study. Subjects consumed either a flavanol-rich chocolate bar and cocoa beverage daily (total flavanols, 444 mg/day) or matching isocaloric placebos daily (total flavanols, 19.6 mg/day) for 6 weeks. Brachial artery FMD (flow-mediated dilation) and SAC (systemic arterial compliance) were assessed at baseline, 90 min following the first beverage and after 3 and 6 weeks of daily consumption. Soluble cellular adhesion molecules and FBF (forearm blood flow) responses to ACh (acetylcholine chloride; 3-30 microg/min) and SNP (sodium nitroprusside; 0.3-3 microg/min) infusions, forearm ischaemia and isotonic forearm exercise were assessed at baseline and after 6 weeks. FMD, SAC and FBF responses did not differ between groups at baseline. No acute or chronic changes in FMD or SAC were seen in either group. No difference in soluble cellular adhesion molecules, FBF responses to ischaemia, exercise, SNP or ACh was seen in the group receiving flavanol-rich cocoa between baseline and 6 weeks. These data suggest that over a 6-week period, flavanol-rich cocoa does not modify vascular function in patients with established CAD.

Bauhinia forficata prevents vacuous chewing movements induced by haloperidol in rats and has antioxidant potential in vitro.

PubMed

Peroza, Luis Ricardo; Busanello, Alcindo; Leal, Caroline Queiroz; Röpke, Jivago; Boligon, Aline Augusti; Meinerz, Daiane; Libardoni, Milena; Athayde, Margareth Linde; Fachinetto, Roselei

2013-04-01

Classical antipsychotics can produce motor disturbances like tardive dyskinesia in humans and orofacial dyskinesia in rodents. These motor side effects have been associated with oxidative stress production in specific brain areas. Thus, some studies have proposed the use of natural compounds with antioxidant properties against involuntary movements induced by antipsychotics. Here, we examined the possible antioxidant activity of Bauhinia forficata (B. forficata), a plant used in folk medicine as a hypoglycemic, on brain lipid peroxidation induced by different pro-oxidants. B. forficata prevented the formation of lipid peroxidation induced by both pro-oxidants tested. However, it was effective against lipid peroxidation induced by sodium nitroprusside (IC50 = 12.08 μg/mL) and Fe(2+)/EDTA (IC50 = 41.19 μg/mL). Moreover, the effects of B. forficata were analyzed on an animal model of orofacial dyskinesia induced by long-term treatment with haloperidol, where rats received haloperidol each 28 days (38 mg/kg) and/or B. forficata decoction daily (2.5 g/L) for 16 weeks. Vacuous chewing movements (VCMs), locomotor and exploratory activities were evaluated. Haloperidol treatment induced VCMs, and co-treatment with B. forficata partially prevented this effect. Haloperidol reduced the locomotor and exploratory activities of animals in the open field test, which was not modified by B. forficata treatment. Our present data showed that B. forficata has antioxidant potential and partially protects against VCMs induced by haloperidol in rats. Taken together, our data suggest the protection by natural compounds against VCMs induced by haloperidol in rats.

Molecular cloning, characterization, and expression of an alfalfa (Medicago sativa L.) heme oxygenase-1 gene, MsHO1, which is pro-oxidants-regulated.

PubMed

Fu, Guang-Qing; Xu, Sheng; Xie, Yan-Jie; Han, Bin; Nie, Li; Shen, Wen-Biao; Wang, Ren

2011-07-01

It has been documented that plant heme oxygenase-1 (HO-1; EC 1.14.99.3) is both development- and stress-regulated, thus it plays a vital role in light signalling and stress responses. In this study, an alfalfa (Medica sativa L.) HO-1 gene MsHO1 was isolated and sequenced. It contains four exons and three introns within genomic DNA sequence and encodes a polypeptide with 283 amino acids. MsHO1 had a conserved HO signature sequence and showed high similarity to other HOs in plants, especially HO-1 isoform. The MsHO1:GFP fusion protein was localized in the chloroplast. Further biochemical activity analysis of mature MsHO1, which was expressed in Escherichia coli, showed that the Vmax was 48.78 nmol biliverdin-IXα (BV) h⁻¹ nmol⁻¹ protein with an apparent Km value for hemin of 2.33 μM, and the optimum Tm and pH were 37 °C and 7.2, respectively. Results of semi-quantitative RT-PCR and western blot showed that the expressions of MsHO1 were higher in alfalfa stems and leaves than those in germinating seeds and roots. Importantly, MsHO1 gene expression and protein level were induced significantly by some pro-oxidant compounds, including hemin and nitric oxide (NO) donor sodium nitroprusside (SNP). In conclusion, MsHO1 may play an important role in oxidative responses. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Gas chromatography coupled with mass spectrometric characterization of Curcuma longa: Protection against pathogenic microbes and lipid peroxidation in rat's tissue homogenate.

PubMed

Hassan, Waseem; Gul, Shehnaz; Rehman, Shakilla; Kanwal, Farina; Afridi, Muhammad Siddique; Fazal, Hina; Shah, Ziarat; Rahman, Ataur; da Rocha, Joao B T

2016-03-01

The present study was designed to investigate the mineral content and antimicrobial activity of Curcuma Longa extracts and its essential oil. We also determined the lipid peroxidation inhibition activity of the ethanolic extract against sodium nitroprusside (SNP) induced thiobarbituric acid reactive species (TBARS) formation in rat's brain, kidney and liver homogenates. Major constituents of essential oil identified by gas chromatography and mass spectrometry (GCMS) were beta-sesquiphellandrene (38.69%), alpha-curcumene (18.44%) and p-mentha-1,4 (8)-diene (16.29%). Atomic absorption spectroscopy (AAS) was used for the quantitative estimation of Calcium (Ca), Magnesium (Mg), Iron (Fe), Copper (Cu), Zinc (Zn), Chromium (Cr), Nickel (Ni) and Manganese (Mn). The extract showed highest Mg (49.4 mg/l) concentration followed by Ca (35.42 mg/l) and Fe (1.27 mg/l). Our data revealed that the ethanolic extract of Curcuma Longa at 1-10 mg/kg significantly inhibited TBARS production in all tested homogenates. Crude extracts and essential oil were tested against three gram positive bacteria i.e. Bacillus subtilis, Bacillus atrophoeus, Staphylococcus aureus, six gram negative bacteria i.e. Escherichia coli, Klebsiella pneumonias, Salmonella typhi, Pseudomonas aeruginosa, Erwinia carotovora, Agrobacterium tumefaciens and one fungal strain namely Candida albicans by disc diffusion assay. Essential oil showed highest anti-microbial activity as compared to the crude extracts. The present study confirms the significant antimicrobial and antioxidant potential of the studied plant, which can be considered as a diet supplement for a variety of oxidative stress induced or infectious diseases.

[Comparative study on the reflex responses of carotid and aortic baroreceptors in the rabbit].

PubMed

Li, Z; Ho, S Y

1989-08-01

In 81 anesthetized rabbits, the baroreflex control of heart rate (HR), hind-limb vascular resistance (HVR) and renal sympathetic nerve activity (RSNA) was observed during arterial baroreceptor loading and unloading by intravenously injecting phenylephrine (PE) and nitroprusside (NP). The results were as follows: (1) An increase of arterial pressure with PE caused reduction in HR, HVR and RSNA, while a decrease of arterial pressure with NP evoked opposite responses. These reflex responses were reproducible. (2) By either carotid baroreceptor denervation (CBRX) or aortic baroreceptor denervation (ABRX), the reflex changes of HR induced by injecting PE and NP were impaired (P less than 0.01), while the reflex responses in HVP remained unchanged. Despite of the enhanced basal RSNA following ABRX or CBRX, the magnitude of reflex inhibition in RSNA during injecting NP was similar to that before denervation, whereas that of the reflex excitation in RSNA during injecting NP was reduced (P less than 0.05). (3) After complete sino-aortic denervation (SAD), the change of arterial pressure following PE or NP injection was enhanced, but the reflex changes in HR, HVR and RSNA were significantly diminished (P less than 0.001). (4) Vagotomy abolished the residual reflex changes observed after SAD. The results indicate that the aortic and carotid baroreceptors may regulate HR in a simple additive manner, while the aortic baroreceptor seems to be more important. Furthermore, both the aortic and carotid baroreceptors may play important roles for the reflex control of HVR and RSNA, and operate mutually by the way of inhibitory summation.

Neurovascular coupling protects neurons against hypoxic injury via inhibition of potassium currents by generation of nitric oxide in direct neuron and endothelium cocultures.

PubMed

Wu, Kun-Wei; Kou, Zeng-Wei; Mo, Jia-Lin; Deng, Xu-Xu; Sun, Feng-Yan

2016-10-15

This study examined the effect of neuron-endothelial coupling on the survival of neurons after ischemia and the possible mechanism underlying that effect. Whole-cell patch-clamp experiments were performed on cortical neurons cultured alone or directly cocultured with brain microvascular endothelial cells (BMEC). Propidium iodide (PI) and NeuN staining were performed to examine neuronal death following oxygen and glucose deprivation (OGD). We found that the neuronal transient outward potassium currents (I A ) decreased in the coculture system, whereas the outward delayed-rectifier potassium currents (I K ) did not. Sodium nitroprusside, a NO donor, enhanced BMEC-induced I A inhibition and nitro-l-arginine methylester, a NOS inhibitor, partially prevented this inhibition. Moreover, the neurons directly cocultured with BMEC showed more resistance to OGD-induced injury compared with the neurons cultured alone, and that neuroprotective effect was abolished by treatment with NS5806, an activator of the I A . These results indicate that vascular endothelial cells assist neurons to prevent hypoxic injury via inhibiting neuronal I A by production of NO in the direct neuron-BMEC coculture system. These results further provide direct evidence of functional coupling between neurons and vascular endothelial cells. This study clearly demonstrates that vascular endothelial cells play beneficial roles in the pathophysiological processes of neurons after hypoxic injury, suggesting that the improvement of neurovascular coupling or functional remodeling may become an important therapeutic target for preventing brain injury. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

[Cellular and molecular biology of ischemic retina].

PubMed

Honda, Y

1996-12-01

We introduce our studies on the retinal ischemia in light of both pre- and post-Noell viewpoints. For several years now, we have employed in vivo intraretinal microelectrodes for this field of experiments. This series of studies on the cat eye revealed that the sensory retina as well as the retinal pigment epithelium is severely damaged after only a ten-minute stoppage of blood flow. This phenomenon in usually masked in the routine electroretinogram, a mass electrical response of the retina monitored from the ocular surface. Our studies, employing cultured amacrine cells from embryonic rat eyes, revealed that ischemic changes in neural cells are induced by an increase in extracellular glutamate. Among the glutamate analogs, N-methyl-D-aspartate (NMDA) is responsive to this change. An influx of calcium through NMDA receptor channels activates nitric oxide synthase (NOS), inducing intracellular nitric oxide (NO) in selected amacrine cells. Nitric oxide reacts with free radicals in the cell and induces peroxinitrite, which is toxic. This cascade triggered by ischemia is interrupted by extracellular zinc, magnesium, hemoglobin, nitroprusside, s-nitrosocysteine, and some NMDA antagonists. In terms of clinical application, there is a possibility that dihydroxyphenylalanine (DOPA), superoxide dismutase (SOD), and catalase (CAT), as well as vitamins B6 and B12, are important candidates for administration before an ischemic attack for prevention of damage to the retinal neurons. Gene expression of NOS, interleukin (IL)-1, IL-6, tumor necrosing factor (TNF), and transforming growth factor (TGF)-beta in the ischemic retina was investigated in order to discover reaction substances common to ischemic change and inflammation.

Evaluation of functioning of mitochondrial electron transport chain with NADH and FAD autofluorescence

PubMed

Danylovych, H V

2016-01-01

We prove the feasibility of evaluation of mitochondrial electron transport chain function in isolated mitochondria of smooth muscle cells of rats from uterus using fluorescence of NADH and FAD coenzymes. We found the inversely directed changes in FAD and NADH fluorescence intensity under normal functioning of mitochondrial electron transport chain. The targeted effect of inhibitors of complex I, III and IV changed fluorescence of adenine nucleotides. Rotenone (5 μM) induced rapid increase in NADH fluorescence due to inhibition of complex I, without changing in dynamics of FAD fluorescence increase. Antimycin A, a complex III inhibitor, in concentration of 1 μg/ml caused sharp increase in NADH fluorescence and moderate increase in FAD fluorescence in comparison to control. NaN3 (5 mM), a complex IV inhibitor, and CCCP (10 μM), a protonophore, caused decrease in NADH and FAD fluorescence. Moreover, all the inhibitors caused mitochondria swelling. NO donors, e.g. 0.1 mM sodium nitroprusside and sodium nitrite similarly to the effects of sodium azide. Energy-dependent Ca2+ accumulation in mitochondrial matrix (in presence of oxidation substrates and Mg-ATP2- complex) is associated with pronounced drop in NADH and FAD fluorescence followed by increased fluorescence of adenine nucleotides, which may be primarily due to Ca2+- dependent activation of dehydrogenases of citric acid cycle. Therefore, the fluorescent signal of FAD and NADH indicates changes in oxidation state of these nucleotides in isolated mitochondria, which may be used to assay the potential of effectors of electron transport chain.

Nonspecific microvascular vasodilation during iontophoresis is attenuated by application of hyperosmolar saline.

PubMed

Asberg, A; Holm, T; Vassbotn, T; Andreassen, A K; Hartmann, A

1999-07-01

Iontophoretic administration of acetylcholine chloride (ACh) and sodium nitroprusside (SNP) combined with laser Doppler skin blood perfusion measurements are used for determination of endothelial-dependent and -independent vasodilation. However, the method is biased by nonspecific vasodilation. The primary aim of this study was to investigate if iontophoresis-induced nonspecific vasodilation may be attenuated by addition of high molar concentrations of NaCl to the iontophoresis solutions. Secondary we investigated the applicability of 5 mol/liter NaCl solution as vehicle for ACh and SNP in this method. Skin perfusion changes were determined for iontophoresis of pure vehicles, deionized water and 5 mol/liter NaCl solution, in 12 healthy volunteers. Responses in skin perfusion to iontophoresis of ACh and SNP dissolved in both vehicles were also investigated. Addition of 5 mol/liter NaCl to deionized water significantly attenuated the nonspecific vasodilation and lowered the potential applied over the skin. The inter- and intraindividual coefficients of variation to ACh and SNP responses became, however, higher using hyperosmolar vehicle. During iontophoresis of SNP (in deionized water) we were unable to distinguish between SNP and vehicle effects. This study shows that the nonspecific vasodilation induced by iontophoresis can be attenuated by addition of 5 mol/liter NaCl, possibly due to lower electrical potential over the skin. However, the variability of the method was not improved. When deionized water was used as vehicle the effect of SNP could not be differentiated from that of the vehicle. This was not the case for ACh. Copyright 1999 Academic Press.

Cryptotanshinone inhibits oxidized LDL-induced adhesion molecule expression via ROS dependent NF-κB pathways

PubMed Central

Zhao, Wenwen; Wu, Chuanhong; Chen, Xiuping

2016-01-01

ABSTRACT Adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, play important roles in the initial stage of atherosclerosis. Cryptotanshinone (CPT), a natural compound isolated from Salvia miltiorrhiza Bunge, exhibits anti-atherosclerotic activity although the underlying mechanisms remain elusive. In this study, the protective effect of CPT against oxidized low-density lipoprotein (ox-LDL)-induced adhesion molecule expression was investigated in human umbilical vein endothelial cells. Ox-LDL significantly induced ICAM-1, VCAM-1, and E-selectin expression at the mRNA and protein levels but reduced eNOS phosphorylation and NO generation, which were reversed by CPT pretreatment. Sodium nitroprusside, a NO donor, N-acetyl-L-cysteine (NAC), a reactive oxygen species (ROS) scavenger, and BAY117082, a NF-κB inhibitor, inhibited ox-LDL-induced ICAM-1, VCAM-1, and E-selectin expression. Ox-LDL-induced ROS production was significantly inhibited by CPT and NAC. Furthermore, ox-LDL activated the NF-κB signaling pathway by inducing phosphorylation of IKKβ and IκBα, promoting the interaction of IKKβ and IκBα, and increasing p65 nuclear translocation, which were significantly inhibited by CPT. In addition, CPT, NAC, and BAY117082 inhibited ox-LDL-induced membrane expression of ICAM-1, VCAM-1, E-selectin, and endothelial–monocyte adhesion and restored eNOS phosphorylation and NO generation. Results suggested that CPT inhibited ox-LDL-induced adhesion molecule expression by decreasing ROS and inhibiting the NF-κB pathways, which provides new insight into the anti-atherosclerotic mechanism of CPT. PMID:26647279

Stent-based nitric oxide delivery reducing neointimal proliferation in a porcine carotid overstretch injury model.

PubMed

Hou, Dongming; Narciso, Hugh; Kamdar, Kirti; Zhang, Ping; Barclay, Bruce; March, Keith L

2005-01-01

The effects of nitric acid (NO) on vessel response to injury include the inhibition of platelet adhesion, platelet aggregation, leukocyte adhesion and smooth muscle cell proliferation. Releasing NO from a stent might reduce the clinical problem of restenosis. The present study was designed to examine whether an NO-eluting covered stent can prevent neointimal formation in a porcine carotid overstretch injury model. The interior of a self-expanding polytetrafluoroethylene (ePTFE)-covered aSpire stent was coated with silicone, which contained 23.6 microg or 54.5 microg sodium nitroprusside (SNP, NO-releasing compound). The stent was implanted into carotid artery. Six pigs were implanted with stents, one high-dose SNP and one uncoated control, following balloon overstretch injury of the carotid artery with a balloon-to-artery ratio of 1.3:1. No local or systemic toxicity was evidenced in the six pigs after carotid artery implantation with either low- or high-dose stents within a week. At day 28, the mean intimal thickness was 0.12 +/- 0.05 mm for NO-eluting stents and 0.43 +/- 0.09 mm for uncoated stents (p = 0.008). The mean neointimal area was reduced from 2.40 +/- 0.39 mm2 for control stents to 0.49 +/- 0.16 mm2 for NO-eluting stents (p < 0.0001), which resulted in a 24% reduction of angiographic vessel narrowing. The NO-eluting ePTFE-covered stent is feasible and effectively reduces in-stent neointimal hyperplasia at 28 days in a porcine carotid overstretch model.

Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channel

PubMed Central

Zhu, Yaohui; Huizinga, Jan D

2008-01-01

Abstract Nitrergic nerves are structurally and functionally associated with ICC. To further understand mechanisms of communication, the hypothesis was investigated that NO might affect large conductance K channels. To that end, we searched for IbTX-sensitive currents in ICC obtained through explant cultures from the mouse small intestine and studied effects of the NOS inhibitor omega N-nitro-L-arginine (LNNA) and the NO donor sodium nitroprusside (SNP). IbTX-sensitive currents acquired in the whole-cell configuration through nystatin perforated patches exhibited high noise levels but relatively low amplitude, whereas currents obtained in the conventional whole-cell configuration exhibited less noise and higher amplitudes; depolarization from −80 to + 40 mV evoked 357 ± 159 pA current in the nystatin perforated patch configuration and 1075 ± 597 pA using the conventional whole-cell configuration. Immunohistochemistry showed that ICC associated with ganglia and Auerbach's plexus nerve fibers were immunoreactive to BK antibodies. The IbTX-sensitive currents were increased by SNP and inhibited by LNNA. BK blockers suppressed spontaneous transit outward currents in ICC. After block of BK currents, or before these currents became prominent, calcium currents were activated by depolarization in the same cells. Their peak amplitude occurred at −25 mV and the currents were increased with increasing extracellular calcium and inhibited by cobalt. The hypothesis is warranted that nitrergic innervation inhibits ICC excitability in part through activation of BK channels. In addition, NO is an intracellular regulator of ICC excitability. PMID:18194464

Hypertensive crisis during pregnancy and postpartum period.

PubMed

Too, Gloria T; Hill, James B

2013-08-01

Hypertension affects 10% of pregnancies, many with underlying chronic hypertension, and approximately 1-2% will undergo a hypertensive crisis at some point during their lives. Hypertensive crisis includes hypertensive urgency and emergency; the American College of Obstetricians and Gynecologists describes a hypertensive emergency in pregnancy as persistent (lasting 15 min or more), acute-onset, severe hypertension, defined as systolic BP greater than 160 mmHg or diastolic BP >110 mmHg in the setting of pre-eclampsia or eclampsia. Pregnancy may be complicated by hypertensive crisis, with lower blood pressure threshold for end-organ damage than non-pregnant patients. Maternal assessment should include a thorough history. Fetal assessment should include heart rate tracing, ultrasound for growth and amniotic assessment, and Doppler evaluation if growth restriction is suspected. Initial management of hypertensive emergency (systolic BP >160 mmHg or diastolic BP >110 mmHg in the setting of pre-eclampsia or eclampsia) generally includes the rapid reduction of blood pressure through the use of intravenous antihypertensive medications, with goal systolic blood pressure between 140 mmHg and 150 mmHg and diastolic pressure between 90 mmHg and 100 mmHg. First-line intravenous drugs include labetalol and hydralazine, but other agents may be used, including esmolol, nicardipine, nifedipine, and, as a last resort, sodium nitroprusside. Among patients with hypertensive urgency, slower blood pressure reduction can be provided with oral agents. The objective of this article is to review the current understanding, diagnosis, and management of hypertensive crisis during pregnancy and the postpartum period. Copyright © 2013 Elsevier Inc. All rights reserved.

Attenuation of Oxidative Damage by Boerhaavia diffusa L. Against Different Neurotoxic Agents in Rat Brain Homogenate.

PubMed

Ayyappan, Prathapan; Palayyan, Salin Raj; Kozhiparambil Gopalan, Raghu

2016-01-01

Due to a high rate of oxidative metabolic activity in the brain, intense production of reactive oxygen metabolite occurs, and the subsequent generation of free radicals is implicated in the pathogenesis of traumatic brain injury, epilepsy, and ischemia as well as chronic neurodegenerative diseases. In the present study, protective effects of polyphenol rich ethanolic extract of Boerhaavia diffusa (BDE), a neuroprotective edible medicinal plant against oxidative stress induced by different neurotoxic agents, were evaluated. BDE was tested against quinolinic acid (QA), 3-nitropropionic acid (NPA), sodium nitroprusside (SNP), and Fe (II)/EDTA complex induced oxidative stress in rat brain homogenates. QA, NPA, SNP, and Fe (II)/EDTA treatment caused an increased level of thiobarbituric acid reactive substances (TBARS) in brain homogenates along with a decline in the activities of antioxidant enzymes. BDE treatment significantly decreased the production of TBARS (p < .05) and increased the activities of antioxidant enzymes like catalase and superoxide dismutase along with increased concentration of non-enzymatic antioxidant, reduced glutathione (GSH). Similarly, BDE caused a significant decrease in the lipid peroxidation (LPO) in the cerebral cortex. Inhibitory potential of BDE against deoxyribose degradation (IC50 value 38.91 ± 0.12 μg/ml) shows that BDE can protect hydroxyl radical induced DNA damage in the tissues. Therefore, B. diffusa had high antioxidant potential that could inhibit the oxidative stress induced by different neurotoxic agents in brain. Since many of the neurological disorders are associated with free radical injury, these data may imply that B. diffusa, functioning as an antioxidant agent, may be beneficial for reducing various neurodegenerative complications.

Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean and obese mothers.

PubMed

Stewart, Frances M; Freeman, Dilys J; Ramsay, Jane E; Greer, Ian A; Caslake, Muriel; Ferrell, William R

2007-03-01

Obesity in pregnancy is increasing and is a risk factor for metabolic pathology such as preeclampsia. In the nonpregnant, obesity is associated with dyslipidemia, vascular dysfunction, and low-grade chronic inflammation. Our aim was to measure microvascular endothelial function in lean and obese pregnant women at intervals throughout their pregnancies and at 4 months after delivery. Plasma markers of endothelial function, inflammation, and placental function and their association with microvascular function were also assessed. Women in the 1st trimester of pregnancy were recruited, 30 with a body mass index (BMI) less than 30 kg/m(2) and 30 with a BMI more than or equal to 30 kg/m(2) matched for age, parity, and smoking status. In vivo endothelial-dependent and -independent microvascular function was measured using laser Doppler imaging in the 1st, 2nd, and 3rd trimesters of pregnancy and at 4 months postnatal. Plasma markers of endothelial activation [soluble intercellular cell adhesion molecule-1 (sVCAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF), and plasminogen activator inhibitor (PAI)-1], inflammation (IL-6, TNFalpha, C-reactive protein, and IL-10), and placental function (PAI-1/PAI-2 ratio) were also assessed at each time point. The pattern of improving endothelial function during pregnancy was the same for lean and obese, but endothelial-dependent vasodilation was significantly lower (P < 0.05) in the obese women at each trimester (51, 41, and 39%, respectively). In the postpartum period, the improvement in endothelial-dependent vasodilation persisted in the lean women but declined to near 1st trimester levels in the obese (lean/obese difference, 115%; P < 0.01). There was a small but significant difference in endothelial-independent vasodilation between the two groups, lean response being greater than obese (P = 0.021), and response declined in both groups in the postpartum period. In multivariate analysis, time of sampling had the most impact on endothelial-independent function [18.5% (adjusted sum of squares expressed as a percentage of total means squared), P < 0.001 for sodium nitroprusside response; 9.8%, P < 0.001 for acetylcholine response], and obesity had the most impact on endothelial-dependent microvascular function (1.7%, P = 0.046 for sodium nitroprusside response; 19.3%, P < 0.001 for acetylcholine response). Time of sampling (11.2%, P < 0.001), IL-6 (4.0%, P = 0.002), and IL-10 (2.4%, P = 0.018) were significant independent contributors to variation in endothelial-dependent microvascular function. When obesity was entered into the model, the association with IL-6 and IL-10 was no longer significant, and obesity explained 6.8% (P < 0.001) of the variability in endothelial-dependent microvascular function. In the 1st trimester, obese women had a significantly higher PAI-1/PAI-2 ratio [obese median (interquartile range), 0.87 (0.54-1.21) vs. lean 0.30 (0.21-0.47), P < 0.001), reflecting the lower PAI-2 levels in obese pregnant women. In a multivariate analysis, 1st trimester BMI (7.6%, P = 0.012), IL-10 (8.2%, P < 0.001), and sVCAM-1 (0.73%, P = 0.007) contributed to the 1st trimester PAI-1/PAI-2 ratio. Obese mothers have a lower endothelium-dependent and -independent vasodilation when compared with lean counterparts. There was a higher PAI-1/ PAI-2 ratio in the 1st trimester in obese women, which improved later in pregnancy. Obese pregnancy is associated with chronic preexisting endothelial activation and impairment of endothelial function secondary to increased production of inflammatory T-helper cells-2 cytokines.

Aqueous extracts of avocado pear (Persea americana Mill.) leaves and seeds exhibit anti-cholinesterases and antioxidant activities in vitro.

PubMed

Oboh, Ganiyu; Odubanjo, Veronica O; Bello, Fatai; Ademosun, Ayokunle O; Oyeleye, Sunday I; Nwanna, Emem E; Ademiluyi, Adedayo O

2016-03-01

Avocado pear (Persea americana Mill.) leaves and seeds are used in traditional medicine for the treatment/management of Alzheimer disease (AD); however, information on the mechanism of actions is limited. This study sought to investigate the effect of P. americana leaf and seed aqueous extracts on some enzymes linked with AD (acetylcholinesterase [AChE] and butyrylcholinesterase [BChE] activities) and their antioxidant potentials in vitro. The inhibitory effects of extracts on AChE and BChE activities and antioxidant potentials (inhibition of Fe2+- and sodium nitroprusside-induced thiobarbiturate reactive species [TBARS] production in rat brain homogenates, radicals [1,1-diphenyl-2-picrylhydrazyl, hydroxyl, and nitric oxide] scavenging and iron [Fe] chelation abilities) were investigated. Phenolic content and phytochemical screening were carried out. Alkaloid profile was also determined using gas chromatography coupled with flame ionization detector (GC-FID). The extracts inhibited AChE and BChE activities and prooxidant-induced TBARS production in a dose-dependent manner, with the seed extract having the highest inhibitory effect and the leaf extract exhibiting higher phenolic content and radical scavenging abilities, but lower Fe chelation ability compared with that of the seed. The phytochemical screening revealed the presence of saponins, alkaloids, and terpenoids in both extracts, whereas the total alkaloid profile was higher in the seed extract than in the leaf extract, as revealed by GC-FID. The anti-cholinesterase and antioxidant activities of avocado leaf and seed could be linked to their phytoconstituents and might be the possible mechanisms underlying their use as a cheap and natural treatment/management of AD. However, these extracts should be further investigated in vivo.

Effect of exogenous nitric oxide on antioxidative system and S-nitrosylation in leaves of Boehmeria nivea (L.) Gaud under cadmium stress.

PubMed

Wang, Dafei; Liu, Yunguo; Tan, Xiaofei; Liu, Hongyu; Zeng, Guangming; Hu, Xinjiang; Jian, Hao; Gu, Yanling

2015-03-01

Cadmium (Cd)-induced growth inhibition is one of the primary factors limiting phytoremediation effect of Boehmeria nivea (L.) Gaud in contaminated soil. Sodium nitroprusside (SNP), a donor of nitric oxide (NO), has been evidenced to alleviate Cd toxicity in many plants. However, as an important mechanism of NO in orchestrating cellular functions, S-nitrosylation is still poorly understood in its relation with Cd tolerance of plants. In this study, higher exogenous NO levels were found to coincide with higher S-nitrosylation level expressed as content of S-nitrosothiols (SNO). The addition of low concentration (100 μM) SNP increased the SNO content, and it simultaneously induced an alleviating effect against Cd toxicity by enhancing the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR) and reduced the accumulation of H2O2 as compared with Cd alone. Application of S-nitrosoglutathione reductase (GSNOR) inhibitors dodecanoic acid (DA) in 100 μM SNP group brought in an extra elevation in S-nitrosylation level and further reinforced the effect of SNP. While the additions of 400 μM SNP and 400 μM SNP + 50 μM DA further elevated the S-nitrosylation level, it markedly weakened the alleviating effect against Cd toxicity as compared with the addition of 100 μM SNP. This phenomenon could be owing to excess consumption of glutathione (GSH) to form SNO under high S-nitrosylation level. Therefore, the present study indicates that S-nitrosylation is involved in the ameliorating effect of SNP against Cd toxicity. This involvement exhibited a concentration-dependent property.

Cross regulation between cGMP-dependent protein kinase and Akt in vasodilatation of porcine pulmonary artery.

PubMed

Liu, Juan; Liu, Huixia; Li, Yanjing; Xu, Xiaojian; Chen, Zhengju; Liu, Limei; Yu, Xiaoxing; Gao, Yuansheng; Dou, Dou

2014-11-01

cGMP-dependent protein kinase (PKG) plays a crucial role in vasodilatation induced by cGMP-elevating agents. Akt has been demonstrated to be involved in modulating vasoreactivity. The present study was to determine the interaction between PKG and Akt and their influences on nitric oxide (NO)-induced vasodilatation. Isolated fourth-generation porcine pulmonary arteries were dissected from the lung and cut into rings in ice-cold modified Krebs-Ringer bicarbonate buffer. The relaxant responses of vessels were determined by organ chamber technique, cGMP was assayed by using enzyme-linked immunosorbent assay kit, the protein levels of phosphorylated Akt were examined by Western blotting, and the activity of phosphodiesterase type 5 (PDE5) was assayed by measuring the rate of cGMP degradation. Incubation with DETA NONOate (a stable NO donor) and 8-Br-cGMP (a cell membrane permeable analog of cGMP) attenuated Akt phosphorylation at Ser-473, which was prevented by Rp-8-Br-PET-cGMPS (a specific inhibitor of PKG) and calyculin A (an inhibitor of protein phosphatase 1 and 2A) but not by okadaic acid (a selective inhibitor of protein phosphatase 2A). Inhibition of Akt enhanced the relaxation and cGMP elevation of porcine pulmonary arteries induced by DETA NONOate or sodium nitroprusside, which was prevented by zaprinast, a specific inhibitor of PDE5. Incubation with LY294002 or Akt inhibitor reduced PDE5 activity in porcine pulmonary arteries. The present study indicates that PKG may attenuate Akt phosphorylation through protein phosphatase 1, which leads to an augmented cGMP elevation by inhibition of PDE5. The increased cGMP in turn activates PKG. Such a positive feedback may play an important role in NO-induced pulmonary vasodilatation.

High-fat diet-induced obesity leads to increased NO sensitivity of rat coronary arterioles: role of soluble guanylate cyclase activation.

PubMed

Jebelovszki, Eva; Kiraly, Csaba; Erdei, Nora; Feher, Attila; Pasztor, Eniko T; Rutkai, Ibolya; Forster, Tamas; Edes, Istvan; Koller, Akos; Bagi, Zsolt

2008-06-01

The impact of obesity on nitric oxide (NO)-mediated coronary microvascular responses is poorly understood. Thus NO-mediated vasomotor responses were investigated in pressurized coronary arterioles ( approximately 100 microm) isolated from lean (on normal diet) and obese (fed with 60% of saturated fat) rats. We found that dilations to acetylcholine (ACh) were not significantly different in obese and lean rats (lean, 83 +/- 4%; and obese, 85 +/- 3% at 1 microM), yet the inhibition of NO synthesis with N(omega)-nitro-l-arginine methyl ester reduced ACh-induced dilations only in vessels of lean controls. The presence of the soluble guanylate cyclase (sGC) inhibitor oxadiazolo-quinoxaline (ODQ) elicited a similar reduction in ACh-induced dilations in the two groups of vessels (lean, 60 +/- 11%; and obese, 57 +/- 3%). Dilations to NO donors, sodium nitroprusside (SNP), and diethylenetriamine (DETA)-NONOate were enhanced in coronary arterioles of obese compared with lean control rats (lean, 63 +/- 6% and 51 +/- 5%; and obese, 78 +/- 5% and 70 +/- 5%, respectively, at 1 microM), whereas dilations to 8-bromo-cGMP were not different in the two groups. In the presence of ODQ, both SNP and DETA-NONOate-induced dilations were reduced to a similar level in lean and obese rats. Moreover, SNP-stimulated cGMP immunoreactivity in coronary arterioles and also cGMP levels in carotid arteries were enhanced in obese rats, whereas the protein expression of endothelial NOS and the sGC beta1-subunit were not different in the two groups. Collectively, these findings suggest that in coronary arterioles of obese rats, the increased activity of sGC leads to an enhanced sensitivity to NO, which may contribute to the maintenance of NO-mediated dilations and coronary perfusion in obesity.

Reactive oxygen species and nitric oxide are involved in polyamine-induced growth inhibition in wheat plants.

PubMed

Recalde, Laura; Vázquez, Analía; Groppa, María D; Benavides, María Patricia

2018-03-06

Polyamines (PAs) produce H 2 O 2 and nitric oxide (NO) during their normal catabolism and modulate plant growth and development. To explore the biochemical basis of PAs-induced growth inhibition in Triticum aestivum L seedlings, we examined the role of O 2 ·- , H 2 O 2 or NO in shoot and root development. Although all PA treatments resulted in a variable reduction of root and shoot elongation, spermine (Spm) caused the greater inhibition in a similar way to that observed with the NO donor, sodium nitroprusside (SNP). In both cases, O 2 ·- production was completely blocked whereas H 2 O 2 formation was high in the root apex under SNP or Spm treatments. Catalase recovered root and shoot growth in SNP but not in Spm-treated plants, revealing the involvement of H 2 O 2 in SNP-root length reduction. The addition of the NO scavenger, cPTIO, restored root length in SNP- or Spm-treated plants, respectively, and partially recovered O 2 ·- levels, compared to the plants exposed to PAs or SNP without cPTIO. A strong correlation was observed between root growth restoration and O 2 ·- accumulation after treating roots with SNP + aminoguanidine, a diamine oxidase inhibitor, and with SNP + 1,8-diaminoctane, a polyamine oxidase inhibitor, confirming the essential role of O 2 ·- formation for root growth and the importance of the origin and level of H 2 O 2 . The differential modulation of wheat growth by PAs through reactive oxygen species or NO is discussed. Graphical abstract Polyamines, nitric oxide and ROS interaction in plants during plant growth.

Neuronal nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo

PubMed Central

Kellogg, Dean L; Zhao, Joan L; Wu, Yubo

2008-01-01

The physiological roles of constituitively expressed nitric oxide synthase (NOS) isoforms in humans, in vivo, are unknown. Cutaneous vasodilatation during both central nervous system-mediated, thermoregulatory reflex responses to whole-body heat stress and during peripheral axon reflex-mediated, local responses to skin warming in humans depend on nitric oxide (NO) generation by constituitively expressed NOS of uncertain isoform. We hypothesized that neuronal NOS (nNOS, NOS I) effects cutaneous vasodilatation during whole-body heat stress, but not during local skin warming. We examined the effects of the nNOS inhibitor 7-nitroindazole (7-NI) administered by intradermal microdialysis on vasodilatation induced by whole-body heat stress or local skin warming. Skin blood flow (SkBF) was monitored by laser–Doppler flowmetry (LDF). Blood pressure (MAP) was monitored and cutaneous vascular conductance calculated (CVC = LDF/MAP). In protocol 1, whole-body heat stress was induced with water-perfused suits. In protocol 2, local skin warming was induced through local warming units at LDF sites. At the end of each protocol, 56 mm sodium nitroprusside was perfused at microdialysis sites to raise SkBF to maximal levels for data normalization. 7-NI significantly attenuated CVC increases during whole-body heat stress (P < 0.05), but had no effect on CVC increases induced by local skin warming (P > 0.05). These diametrically opposite effects of 7-NI on two NO-dependent processes verify selective nNOS antagonism, thus proving that the nNOS isoform affects NO increases and hence vasodilatation during centrally mediated, reflex responses to whole-body heat stress, but not during locally mediated, axon reflex responses to local skin warming. We conclude that the constituitively expressed nNOS isoform has distinct physiological roles in cardiovascular control mechanisms in humans, in vivo. PMID:18048451

Dual implantation of a radio-telemeter and vascular access port allows repeated hemodynamic and pharmacological measures in conscious lean and obese rats.

PubMed

Bussey, C T; Leeuw, A E de; Cook, R F; Ashley, Z; Schofield, J; Lamberts, R R

2014-07-01

Expansion of physiological knowledge increasingly requires examination of processes in the normal, conscious state. The current study describes a novel approach combining surgical implantation of radio-telemeters with vascular access ports (VAPs) to allow repeated hemodynamic and pharmacological measures in conscious rats. Dual implantation was conducted on 16-week-old male lean and obese Zucker rats. Continued viability one month after surgery was observed in 67% of lean and 44% of obese animals, giving an overall 54% completion rate. Over the five-week measurement period, reliable and reproducible basal mean arterial pressure and heart rate measures were observed. VAP patency and receptor-independent vascular reactivity were confirmed by consistent hemodynamic responses to sodium nitroprusside (6.25 µg/kg). Acutely, minimal hemodynamic responses to repeated bolus administration of 0.2 mL saline indicated no significant effect of increased blood volume or administration stress, making repeated acute measures viable. Similarly, repeated administration of the β-adrenoceptor agonist dobutamine (30 µg/kg) at 10 min intervals resulted in reproducible hemodynamic changes in both lean and obese animals. Therefore, our study demonstrates that this new approach is viable for the acute and chronic assessment of hemodynamic and pharmacological responses in both lean and obese conscious rats. This technique reduces the demand for animal numbers and allows hemodynamic measures with minimal disruption to animals' welfare, while providing reliable and reproducible results over several weeks. In conclusion, dual implantation of a radio-telemeter and VAP introduces a valuable technique for undertaking comprehensive studies involving repeated pharmacological tests in conscious animals to address important physiological questions. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels.

PubMed

Roberts, R E; Allen, S; Chang, A P Y; Henderson, H; Hobson, G C; Karania, B; Morgan, K N; Pek, A S Y; Raghvani, K; Shee, C Y; Shikotra, J; Street, E; Abbas, Z; Ellis, K; Heer, J K; Alexander, S P H

2013-11-01

German chamomile (Matricaria recutita L.), a widely-used herbal medicine, has been reported to have a wide range of biological effects, including smooth muscle relaxation. The aim of this study was to compare the effects of representative compounds from chamomile (apigenin, luteolin, (-)-α-bisabolol, farnesene, umbelliferone; 3-30 μM) on vascular tone using porcine coronary and splenic arteries mounted for isometric tension recording in isolated tissue baths and precontracted with the thromboxane-mimetic U46619. Apigenin, luteolin, and (-)-α-bisabolol produced slow, concentration-dependent relaxations in both the coronary and splenic arteries that were not blocked by inhibition of nitric oxide synthase or potassium channels. Removal of extracellular calcium inhibited the relaxations to all three compounds, and these compounds also inhibited calcium re-addition-evoked contractions, indicating that the relaxation response may be mediated through inhibition of calcium influx. Apigenin and luteolin, but not (-)-α-bisabolol, enhanced the relaxation to the nitric oxide donor sodium nitroprusside, indicating that apigenin and luteolin may act to regulate cyclic GMP levels. Umbelliferone produced a rapid, transient relaxation in the splenic artery, but not the coronary artery, that was inhibited by L-NAME and removal of the endothelium, suggesting an influence on nitric oxide production. Farnesene, at concentrations up to 30 μM, was without effect in either blood vessel. In conclusion, hydroxylated compounds (apigenin, luteolin and (-)-α-bisabolol) found in chamomile all caused a slow relaxation of isolated blood vessels through an effect on calcium influx. Umbelliferone, on the other hand, produced a rapid, transient relaxation dependent upon release of nitric oxide from the endothelium. © 2013.

Creatine affords protection against glutamate-induced nitrosative and oxidative stress.

PubMed

Cunha, Mauricio P; Lieberknecht, Vicente; Ramos-Hryb, Ana Belén; Olescowicz, Gislaine; Ludka, Fabiana K; Tasca, Carla I; Gabilan, Nelson H; Rodrigues, Ana Lúcia S

2016-05-01

Creatine has been reported to exert beneficial effects in several neurodegenerative diseases in which glutamatergic excitotoxicity and oxidative stress play an etiological role. The purpose of this study was to investigate the protective effects of creatine, as compared to the N-Methyl-d-Aspartate (NMDA) receptor antagonist dizocilpine (MK-801), against glutamate or hydrogen peroxide (H2O2)-induced injury in human neuroblastoma SH-SY5Y cells. Exposure of cells to glutamate (60-80 mM) or H2O2 (200-300 μM) for 24 h decreased cellular viability and increased dichlorofluorescein (DCF) fluorescence (indicative of increased reactive oxygen species, ROS) and nitric oxide (NO) production (assessed by mono-nitrogen oxides, NOx, levels). Creatine (1-10 mM) or MK-801 (0.1-10 μM) reduced glutamate- and H2O2-induced toxicity. The protective effect of creatine against glutamate-induced toxicity involves its antioxidant effect, since creatine, similar to MK-801, prevented the increase on DCF fluorescence induced by glutamate or H2O2. Furthermore, creatine or MK-801 blocked glutamate- and H2O2-induced increases in NOx levels. In another set of experiments, the repeated, but not acute, administration of creatine (300 mg/kg, po) in mice prevented the decreases on cellular viability and mitochondrial membrane potential (assessed by tetramethylrhodamine ethyl ester, TMRE, probe) of hippocampal slices incubated with glutamate (10 mM). Creatine concentration-dependent decreased the amount of nitrite formed in the reaction of oxygen with NO produced from sodium nitroprusside solution, suggesting that its protective effect against glutamate or H2O2-induced toxicity might be due to its scavenger activity. Overall, the results suggest that creatine may be useful as adjuvant therapy for neurodegenerative disease treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Possible involvement of endothelium-derived hyperpolarizing factor (EDHF) in the depressor responses to platelet activating factor (PAF) in rats

PubMed Central

Tanaka, Yoshio; Hayakawa, Sachiko; Imai, Toshiyasu; Akutsu, Aya; Hirano, Haruko; Tanaka, Hikaru; Nakahara, Tsutomu; Ishii, Kunio; Shigenobu, Koki

2000-01-01

In anaesthetized rats, platelet activating factor (PAF; 1 μg kg−1) decreased mean arterial blood pressure by around 60 mmHg (n=18). This depressor response was completely blocked by the PAF antagonist, CV-6209 (1 mg kg−1), indicating the role of PAF-specific receptor in the response.NG-nitro-L-arginine methyl ester (L-NAME; 50 mg kg−1), an NO synthase inhibitor, profoundly elevated systemic blood pressure (n=19), indicating an important role of NO in the basal blood pressure regulation. The depressor response to PAF (1 μg kg−1) normalized against that to sodium nitroprusside (SNP) (10 μg kg−1) was not substantially different between rats treated without and with L-NAME (n=4). In contrast, the depressor effect of acetylcholine (0.03–1.0 μg kg−1) normalized against that of SNP (10 μg kg−1) was significantly attenuated by L-NAME (n=5).Charybdotoxin (0.4 mg kg−1) plus apamin (0.2 mg kg−1) significantly attenuated the depressor response to PAF (1 μg kg−1) (n=5) without affecting the blood pressure change due to SNP (1 mg kg−1) (n=3). Charybdotoxin (0.4 mg kg−1) (n=4) or apamin (0.2 mg kg−1) (n=4) alone did not affect the PAF-induced depressor response.These findings suggest that EDHF may make a significant contribution to the depressor response to PAF in rats. Although NO plays the determinant role in the basal blood pressure regulation, its contribution to PAF-produced depressor response seems to be less as compared with that to the depressor response to acetylcholine. PMID:11082118

Nitric oxide generated by nitrate reductase increases nitrogen uptake capacity by inducing lateral root formation and inorganic nitrogen uptake under partial nitrate nutrition in rice

PubMed Central

Sun, Huwei; Li, Jiao; Song, Wenjing; Tao, Jinyuan; Huang, Shuangjie; Chen, Si; Hou, Mengmeng; Xu, Guohua; Zhang, Yali

2015-01-01

Increasing evidence shows that partial nitrate nutrition (PNN) can be attributed to improved plant growth and nitrogen-use efficiency (NUE) in rice. Nitric oxide (NO) is a signalling molecule involved in many physiological processes during plant development and nitrogen (N) assimilation. It remains unclear whether molecular NO improves NUE through PNN. Two rice cultivars (cvs Nanguang and Elio), with high and low NUE, respectively, were used in the analysis of NO production, nitrate reductase (NR) activity, lateral root (LR) density, and 15N uptake under PNN, with or without NO production donor and inhibitors. PNN increased NO accumulation in cv. Nanguang possibly through the NIA2-dependent NR pathway. PNN-mediated NO increases contributed to LR initiation, 15NH4 +/15NO3 – influx into the root, and levels of ammonium and nitrate transporters in cv. Nanguang but not cv. Elio. Further results revealed marked and specific induction of LR initiation and 15NH4 +/15NO3 – influx into the roots of plants supplied with NH4 ++sodium nitroprusside (SNP) relative to those supplied with NH4 + alone, and considerable inhibition upon the application of cPTIO or tungstate (NR inhibitor) in addition to PNN, which is in agreement with the change in NO fluorescence in the two rice cultivars. The findings suggest that NO generated by the NR pathway plays a pivotal role in improving the N acquisition capacity by increasing LR initiation and the inorganic N uptake rate, which may represent a strategy for rice plants to adapt to a fluctuating nitrate supply and increase NUE. PMID:25784715

Apixaban Enhances Vasodilatation Mediated by Protease-Activated Receptor 2 in Isolated Rat Arteries

PubMed Central

Villari, Ambra; Giurdanella, Giovanni; Bucolo, Claudio; Drago, Filippo; Salomone, Salvatore

2017-01-01

Apixaban (APX) is a direct inhibitor of factor X (FXa) approved for prophylaxis and treatment of deep venous thrombosis and atrial fibrillation. Because FXa activates protease-activated receptor 2 (PAR-2) in endothelium and vascular smooth muscle, inhibition of FXa by APX may affect vasomotor function. The effect of APX was assessed in vitro, by wire myography, in rat mesenteric resistance arteries (MRAs) and basilar arteries challenged with vasoconstrictors [phenylephrine (PE); 5-hydroxytryptamine (5-HT)], vasodilators [acetylcholine (ACh); sodium nitroprusside (SNP)] or with the PAR-2 peptide agonist SLIGRL. APX (10 μM) reduced the vasoconstriction to PE and 5-HT while did not change the vasodilatation to ACh or SNP. SLIGRL induced concentration-dependent vasodilation in pre-constricted arteries, that was reduced by incubation with the NO inhibitor NG-nitro-L-arginine (L-NNA) and abolished by endothelium removal. APX enhanced vasodilation to SLIGRL either in the presence or in the absence of L-NNA, but was ineffective in endothelium-denuded vessels. In preparations from heparin-treated rats (to inhibit FXa) APX did not change the vasodilation to SLIGRL. FXa enzymatic activity, detected in mesentery homogenates from controls, was inhibited by APX, whereas APX-sensitive enzymatic activity was undetectable in homogenates from heparin-treated rats. Immunoblot analysis showed that incubation of MRA or aorta with APX increased the abundance of PAR-2, an effect not seen in MRA from heparin-treated rats or in endothelium-denuded aortas. In conclusion, inhibition of FXa by APX increases vasodilatation mediated by PAR-2. APX may act by inhibiting PAR-2 desensitization induced by endogenous FXa. This effect could be useful in the context of endothelial dysfunction associated to cardiovascular diseases. PMID:28769809