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Sample records for endothelium-dependent relaxation responses

  1. Endothelium-dependent relaxation of blood vessels

    SciTech Connect

    Hynes, M.R.

    1987-01-01

    Dilation of blood vessels in response to a large number of agents has been shown to be dependent on an intact vascular endothelium. The present studies examine some aspects of endothelium-dependent vasodilation in blood vessels of the rabbit and rat. Using the rabbit ear artery and the subtype-selective muscarinic antagonist pirenzepine, muscarinic receptors of the endothelium and smooth muscle cells were shown to be of the low affinity M/sub 2/ subtype. Inhibition of (/sup 3/H)(-)quinuclidinyl benzilate was used to determine affinity for the smooth muscle receptors while antagonism of methacholine induced vasodilation yielded the endothelial cell receptor affinity. The effect of increasing age (1-27 months) on endothelium-dependent relaxation was studied in aortic rings, perfused tail artery and perfused mesenteric bed of the Fisher 344 rat. The influence of endothelium on contractile responses was examined using the perfused caudal artery.

  2. Marginal copper deficiency impairs endothelium-dependent relaxation responses across two generations

    USDA-ARS?s Scientific Manuscript database

    The generational effects of marginal copper (Cu) deficiency on vascular function have not been characterized.In this study, the vascular consequences of marginal Cu deficiency were determined by relaxation responses in mesenteric arteries of dams and two generations of offspring. Pups from dams (fir...

  3. Ultrasonic Measurement of Change in Elasticity due to Endothelium Dependent Relaxation Response by Accurate Detection of Artery-Wall Boundary

    NASA Astrophysics Data System (ADS)

    Kaneko, Takuya; Hasegawa, Hideyuki; Kanai, Hiroshi

    2007-07-01

    Ross hypothesized that an endothelial dysfunction is considered to be an initial step in atherosclerosis. Endothelial cells, which release nitric oxide (NO) in response to shear stress from blood flow, have a function of relaxing smooth muscle in the media of the arterial wall. For the assessment of the endothelial function, there is a conventional method in which the change in the diameter of the brachial artery caused by flow-mediated dilation (FMD) is measured with ultrasound. However, despite the fact that the collagen-rich hard adventitia does not respond to NO, the conventional method measures the change in diameter depending on the mechanical property of the entire wall including the adventitia. Therefore, we developed a method of measuring the change in the thickness and the elasticity of the brachial artery during a cardiac cycle using the phased tracking method for the evaluation of the mechanical property of only the intima-media region. In this study, the initial positions of echoes from the lumen-intima and media-adventitia boundaries are determined using complex template matching to accurately estimate the minute change in the thickness and the elasticity of the brachial and radial arteries. The ambiguity in the determination of such boundaries was eliminated using complex template matching, and the change in elasticity measured by the proposed method was larger than the change in inner diameter obtained by the conventional method.

  4. Human obesity and endothelium-dependent responsiveness

    PubMed Central

    Campia, Umberto; Tesauro, Manfredi; Cardillo, Carmine

    2012-01-01

    Obesity is an ongoing worldwide epidemic. Besides being a medical condition in itself, obesity dramatically increases the risk of development of metabolic and cardiovascular disease. This risk appears to stem from multiple abnormalities in adipose tissue function leading to a chronic inflammatory state and to dysregulation of the endocrine and paracrine actions of adipocyte-derived factors. These, in turn, disrupt vascular homeostasis by causing an imbalance between the NO pathway and the endothelin 1 system, with impaired insulin-stimulated endothelium-dependent vasodilation. Importantly, emerging evidence suggests that the vascular dysfunction of obesity is not just limited to the endothelium, but also involves the other layers of the vessel wall. In particular, obesity-related changes in medial smooth muscle cells seem to disrupt the physiological facilitatory action of insulin on the responsiveness to vasodilator stimuli, whereas the adventitia and perivascular fat appear to be a source of pro-inflammatory and vasoactive factors that may contribute to endothelial and smooth muscle cell dysfunction, and to the pathogenesis of vascular disease. While obesity-induced vascular dysfunction appears to be reversible, at least in part, with weight control strategies, these have not proved sufficient to prevent the metabolic and cardiovascular complication of obesity on a large scale. While a number of currently available drugs have shown potentially beneficial vascular effects in patients with obesity and the metabolic syndrome, elucidation of the pathophysiological mechanisms underlying vascular damage in obese patients is necessary to identify additional pharmacologic targets to prevent the cardiovascular complications of obesity, and their human and economic costs. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3 PMID:21895631

  5. Human obesity and endothelium-dependent responsiveness.

    PubMed

    Campia, Umberto; Tesauro, Manfredi; Cardillo, Carmine

    2012-02-01

    Obesity is an ongoing worldwide epidemic. Besides being a medical condition in itself, obesity dramatically increases the risk of development of metabolic and cardiovascular disease. This risk appears to stem from multiple abnormalities in adipose tissue function leading to a chronic inflammatory state and to dysregulation of the endocrine and paracrine actions of adipocyte-derived factors. These, in turn, disrupt vascular homeostasis by causing an imbalance between the NO pathway and the endothelin 1 system, with impaired insulin-stimulated endothelium-dependent vasodilation. Importantly, emerging evidence suggests that the vascular dysfunction of obesity is not just limited to the endothelium, but also involves the other layers of the vessel wall. In particular, obesity-related changes in medial smooth muscle cells seem to disrupt the physiological facilitatory action of insulin on the responsiveness to vasodilator stimuli, whereas the adventitia and perivascular fat appear to be a source of pro-inflammatory and vasoactive factors that may contribute to endothelial and smooth muscle cell dysfunction, and to the pathogenesis of vascular disease. While obesity-induced vascular dysfunction appears to be reversible, at least in part, with weight control strategies, these have not proved sufficient to prevent the metabolic and cardiovascular complication of obesity on a large scale. While a number of currently available drugs have shown potentially beneficial vascular effects in patients with obesity and the metabolic syndrome, elucidation of the pathophysiological mechanisms underlying vascular damage in obese patients is necessary to identify additional pharmacologic targets to prevent the cardiovascular complications of obesity, and their human and economic costs. This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3. © 2011 The Authors. British

  6. Depression of endothelium-dependent relaxation in aorta from rats with Brugia pahangi lymphatic filariasis.

    PubMed

    Kaiser, L; Tithof, P K; Lamb, V L; Williams, J F

    1991-06-01

    A role for altered endothelial cell function is emerging in the pathogenesis of disease. We have previously demonstrated that Dirofilaria immitis, the canine heartworm, depresses endothelium-dependent responses and alters the mechanism of relaxation in the in vivo femoral artery of infected dogs. Exposure of rat aorta to the parasite or parasite-conditioned medium selectively depresses endothelium-dependent relaxation. D. immitis is closely related to the major human filarial pathogens. This study was designed to examine the effect of chronic infection with the filarial nematode Brugia pahangi on endothelium-mediated responses of the rat aorta in vitro. We tested the hypothesis that endothelium-dependent responses are depressed in the aorta from rats infected with B. pahangi. Rings of thoracic and abdominal aorta were suspended in muscle baths for measurement of isometric tension. Dose-response relations to norepinephrine, endothelium-dependent dilators (acetylcholine, histamine, and A23187), and nitroglycerin were done. In some experiments, inhibitors of cyclooxygenase (indomethacin and aspirin), guanylate cyclase (methylene blue), and nitric oxide formation (N-nitro-L-arginine methyl ester; L-NOARG) were used. No differences in vascular reactivity were detected in the thoracic aorta. In contrast, endothelium-dependent responses in abdominal aorta of Brugia-infected rats were significantly depressed when compared with control aorta from noninfected rats. Acetylcholine relaxation was further depressed by indomethacin and aspirin. After L-NOARG, acetylcholine relaxation in control abdominal aorta was completely abolished; however, in abdominal aorta of Brugia-infected rats, acetylcholine still caused relaxation. Methylene blue inhibited acetylcholine relaxation in both control and Brugia-infected abdominal aorta; however, relaxation in Brugia-infected aorta was significantly greater than control. This study demonstrates that endothelium-dependent relaxation can be

  7. L-Carnitine supplementation impairs endothelium-dependent relaxation in mesenteric arteries from rats.

    PubMed

    Valgas da Silva, Carmem P; Rojas-Moscoso, Julio A; Antunes, Edson; Zanesco, Angelina; Priviero, Fernanda B M

    2014-07-01

    L-Carnitine (L-Car) is taken as fat burner. The risks of L-Car supplementation for the cardiovascular system are unclear. We evaluated the relaxing responses of the mesenteric and aorta rings from rats after four weeks of L-Car supplementation and/or physical training. Concentration response curves to acetylcholine (ACh) and sodium nitroprusside (SNP), as well as cyclic GMP levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) were evaluated. Physical training decreased body weight gain that was potentiated by L-Car. In mesenteric rings, L-Car impaired endothelium-dependent relaxation whereas endothelium independent relaxation was increased. In aorta, exercise improved endothelium-dependent relaxation; however, it was partially inhibited by L-Car. SNP-induced relaxation was similar in aorta of all groups. Basal cGMP were increased in aorta of exercised rats. SOD activity and MDA levels were unaltered. In conclusion, L-Car and physical exercise promotes body weight loss; however, it impairs endothelium-dependent vaso-relaxation possibly involving alterations in muscarinic receptors/eNOS/NO signalling pathway in mesenteric artery.

  8. (-)epicatechin induces and modulates endothelium-dependent relaxation in isolated rat mesenteric artery rings.

    PubMed

    Chen, Zhen-Yu; Yao, Xiao-Qiang; Chan, Franky Leung; Lau, Chi-Wai; Huang, Yu

    2002-12-01

    The present study was aimed to examine the role of endothelial nitric oxide in the relaxant response to green tea (-)epicatechin and its modulation of endothelium-mediated relaxation in the isolated rat mesenteric artery rings. Changes in the isometric tension were measured with Grass force-displacement transducers. The (-)epicatechin-induced relaxation was largely dependent on the presence of intact endothelium and was reversed by NG-nitro-L-arginine methyl ester 10 micromol/L or methylene blue 10 micromol/L, the inhibitors of nitric oxide-mediated relaxation. L-Arginine at 1 mmol/L antagonized the effect of L-NAME or methylene blue. Pretreatment of endothelium-intact rings with (-)epicatechin 10 micromol/L enhanced the relaxation induced by endothelium-dependent vasodilator, acetylcholine, while this concentration did not influence the endothelium-independent relaxation induced by sodium nitroprusside in the endothelium-denuded artery rings. The results indicate that the endothelium-dependent vasodilation by (-)epicatechin is mainly mediated through nitric oxide and low concentration of (-)epicatechin augments endothelium-dependent vasorelaxation in the rat mesenteric arteries.

  9. Selective impairment of endothelium-dependent relaxation by sevoflurane: oxygen free radicals participation.

    PubMed

    Yoshida, K; Okabe, E

    1992-03-01

    To determine whether sevoflurane alters endothelium-mediated vasodilation of vascular smooth muscle, isolated ring preparations of canine mesenteric arteries were suspended for isometric tension recordings in modified Krebs-Ringer bicarbonate solution at 37 degrees C. Following contraction with norepinephrine, cumulative concentration-response curves were generated using endothelium-dependent vasodilators (acetylcholine, bradykinin, and calcium ionophore A23187) or nitroglycerin. The relaxation produced by acetylcholine, bradykinin, or A23187 was impaired by sevoflurane (2.3 and 4.6 vol%); sevoflurane did not affect relaxation caused by nitroglycerin, which, in these vessels, acts by an endothelium-independent mechanism. Under the same experimental conditions as those used for the concentration-response relationship, electron spin resonance spin-trapping with 5,5-dimethyl-1-pyrroline N-oxide verified generation of hydroxyl radical from the sevoflurane-delivered bathing media; the generation of hydroxyl radical was inhibited by superoxide dismutase, a scavenger of superoxide anion radical, or by the powerful iron chelator deferoxamine. Furthermore, sevoflurane-induced impairment of the relaxation caused by the endothelium-dependent vasodilators used was significantly decreased by superoxide dismutase. These results indicate that superoxide anion radical and/or closely related species of oxygen free radicals, possibly hydroxyl radical, are involved in the observed effect of sevoflurane. We propose that sevoflurane selectively impairs endothelium-dependent relaxation in canine mesenteric arteries by an oxygen free radical mechanism, mainly due to inactivation of endothelium-derived relaxing factor.

  10. Epoxyeicosatrienoic Acids and Endothelium-Dependent Responses

    PubMed Central

    Campbell, William B.; Fleming, Ingrid

    2012-01-01

    Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic acid that are produced by the vascular endothelium in response to agonists such as bradykinin and acetylcholine or physical stimuli such as shear stress or cyclic stretch. In the vasculature, the EETs have biological actions that are involved in the regulation of vascular tone, hemostasis and inflammation. In pre-constricted arteries in vitro, EETs activate calcium-activated potassium channels on vascular smooth muscle and the endothelium causing membrane hyperpolarization and relaxation. These effects are observed in a variety of arteries from experimental animals and humans; however, this is not a universal finding in all arteries. The mechanism of EET action may vary. In some arteries, EETs are released from the endothelium and are transferred to the smooth muscle where they cause potassium channel activation, hyperpolarization and relaxation through a G-protein coupled mechanism or transient receptor potential (TRP) channel activation. In other arteries, EETs activate TRP channels on the endothelium to causes endothelial hyperpolarization that is transferred to the smooth muscle by gap junctions or potassium ion. Some arteries use a combination of mechanisms. Acetylcholine and bradykinin increase blood flow in dogs and humans that is inhibited by potassium channel blockers and cytochrome P450 inhibitors. Thus, the EETs are endothelium-derived hyperpolarizing factors mediating a portion of the relaxations to acetylcholine, bradykinin, shear stress and cyclic stretch and regulate vascular tone in vitro and in vivo. PMID:20224870

  11. Effects of indapamide on endothelium-dependent relaxations in isolated canine femoral arteries.

    PubMed

    Schini, V B; Dewey, J; Vanhoutte, P M

    1990-05-02

    Indapamide is an effective antihypertensive agent in humans and in experimental hypertensive animals. The aim of the present study was to investigate whether indapamide affects endothelium-dependent and independent relaxations in canine femoral arteries. Rings (with or without endothelium) were contracted with prostaglandin F2 alpha (2 X 10(-6) mol/liter) before the addition, in a cumulative fashion, of relaxing agents. Indapamide (10(-7) to 10(-4) mol/liter) had no direct effect on unstimulated or prostaglandin-stimulated preparations; it did not alter relaxations of preparations with endothelium induced by acetylcholine, bradykinin, adenosine diphosphate or the calcium ionophore A23187. Similarly, it did not affect relaxations induced by sodium nitroprusside, prostacyclin or forskolin in preparations with or without endothelium. Indomethacin shifted the concentration-response curve to bradykinin to the right and did not alter that to the other relaxing drugs. The reduced relaxation to bradykinin was reversed in a concentration-dependent manner by indapamide (10(-7) to 10(-5) mol/liter). In the presence of indomethacin, indapamide shifted the concentration response curve to prostacyclin (in rings with endothelium) and to forskolin (in rings with and without endothelium) to the left. Thus, indapamide does not directly affect endothelium-dependent and independent relaxations. However, when prostanoid production is impaired, indapamide facilitates the release of endothelium-derived relaxing factor(s), and to a lesser extent, the direct action on vascular smooth muscle of prostanoids (prostacyclin) released from the endothelium.

  12. Endothelium-dependent responses in isolated blood vessels of lower vertebrates.

    PubMed

    Miller, V M; Vanhoutte, P M

    1986-01-01

    Endothelium-dependent relaxations to acetylcholine have been identified in mammalian arteries and veins. To determine the occurrence of such relaxations in other classes of vertebrates, rings of descending aortas of turtles, cayman and bullfrogs and ventral aortas of trout were suspended for isometric force measurements. Acetylcholine and the calcium ionophore A23187 initiated concentration-dependent relaxations in aortas from cayman and bullfrogs contracted with norepinephrine. These relaxations were not affected by meclofenamate, were reversed by methylene blue and abolished by endothelium removal. Acetylcholine caused concentration-dependent contractions in aortas (with and without endothelium) from trout and turtles; these tissues contracted minimally to norepinephrine. In the aortas of the trout contracted with acetylcholine, the calcium ionophore A23187 initiated endothelium-dependent relaxations which were reversed by methylene blue and abolished by meclofenamate. A23187 contracted turtle aortas; an effect reduced by endothelium removal. These data demonstrate endothelium-dependent relaxations and contractions in blood vessels of reptiles, amphibians and teleosts. Thus, endothelium-dependent modulation of the responses of the vascular smooth muscle represents a cardiovascular regulatory mechanism which appears early in vertebrate phylogeny.

  13. Abnormal endothelium-dependent responses in early radiation nephropathy.

    PubMed

    Juncos, L I; Cornejo, J C; Gomes, J; Baigorria, S; Juncos, L A

    1997-09-01

    While arterial hypertension and renal dysfunction are well recognized complications of renal irradiation, the mechanisms that trigger the development of these complications are unknown. Recently, it was reported that the endothelium is a major target in radiation injury. Because dysfunction of the endothelial cells may lead or contribute to the development of hypertension and renal dysfunction in radiation nephropathy, we tested the hypothesis that endothelium-dependent vasodilation is impaired in radiated kidneys prior to the onset of hypertension. To test this hypothesis, we used Long-Evans rats that had undergone left nephrectomy (3 weeks earlier) and irradiation (3000 r's) to the right kidney 8 days earlier (mean blood pressures in the irradiated rats were not different than in the controls). We then measured the changes in renal blood flow (RBF) induced by endothelium-dependent (acetylcholine and bradykinin) and -independent (nitroprusside, norepinephrine, and angiotensin II) vasoactive agents. We found that the increases in RBF induced by the endothelium-dependent but not independent vasodilators were markedly impaired in the irradiated kidneys. Blocking nitric oxide synthesis with nitro L-arginine methyl ester in sham rats mimicked the blunted responsiveness of the irradiated rats, whereas indomethacin (an inhibitor of prostaglandin synthesis) had no effect on either sham or irradiated rats. Finally, the RBF responses to the endothelium-independent vasoconstrictors, norepinephrine and angiotensin II, were not altered in the irradiated kidneys. These results suggest that renal irradiation causes endothelial dysfunction (prior to the onset of hypertension) but spares the vascular smooth muscle cells.

  14. Physical activity maintains aortic endothelium-dependent relaxation in the obese type 2 diabetic OLETF rat.

    PubMed

    Bunker, Aaron K; Arce-Esquivel, Arturo A; Rector, R Scott; Booth, Frank W; Ibdah, Jamal A; Laughlin, M Harold

    2010-06-01

    We tested the hypothesis that physical activity can attenuate the temporal decline of ACh-induced endothelium-dependent relaxation during type 2 diabetes mellitus progression in the Otsuka Long-Evans Tokushima fatty (OLETF) rat. Sedentary OLETF rats exhibited decreased ACh-induced abdominal aortic endothelium-dependent relaxation from 13 to 20 wk of age (20-35%) and from 13 to 40 wk of age (35-50%). ACh-induced endothelium-dependent relaxation was maintained in the physically active OLETF group and control sedentary Long-Evans Tokushima Otsuka (LETO) group from 13 to 40 wk of age. Aortic pretreatment with N(G)-nitro-l-arginine (l-NNA), indomethacin (Indo), and l-NNA + Indo did not alter the temporal decline in ACh-induced endothelium-dependent relaxation. Temporal changes in the protein expression of SOD isoforms in the aortic endothelium or smooth muscle did not contribute to the temporal decline in ACh-induced endothelium-dependent relaxation in sedentary OLETF rats. A significant increase in the 40-wk-old sedentary LETO and physically active OLETF rat aortic phosphorylated endothelial nitric oxide (p-eNOS)-to-eNOS ratio was observed versus 13- and 20-wk-old rats in each group that was not seen in the 40- versus 13- and 20-wk-old sedentary OLETF rats. These results suggest that temporal changes in the antioxidant system, EDHF, and cycloxygenase metabolite production in sedentary OLETF rat aortas do not contribute to the temporal decline in sedentary OLETF rat aortic ACh-induced endothelium-dependent relaxation seen with type 2 diabetes mellitus progression. We also report that physical activity in conjunction with aging in the OLETF rat results in a temporal increase in the aortic endothelial p-eNOS-to-eNOS ratio that was not seen in sedentary OLETF rats. These results suggest that the sustained aortic ACh-induced endothelium-dependent relaxation in aged physically active OLETF rats may be the result of an increase in active aortic eNOS.

  15. Alterations in endothelium-dependent hyperpolarization and relaxation in mesenteric arteries from streptozotocin-induced diabetic rats

    PubMed Central

    Fukao, Mitsuhiro; Hattori, Yuichi; Kanno, Morio; Sakuma, Ichiro; Kitabatake, Akira

    1997-01-01

    The aim of this study was to determine whether endothelium-dependent hyperpolarization and relaxation are altered during experimental diabetes mellitus. Membrane potentials were recorded in mesenteric arteries from rats with streptozotocin-induced diabetes and age-matched controls. The resting membrane potentials were not significantly different between control and diabetic mesenteric arteries (−55.3±0.5 vs −55.6±0.4 mV). However, endothelium-dependent hyperpolarization produced by acetylcholine (ACh; 10−8–10−5 M) was significantly diminished in amplitude in diabetic arteries compared with that in controls (maximum −10.4±1.1 vs −17.2±0.8 mV). Furthermore, the hyperpolarizing responses of diabetic arteries were more transient. ACh-induced hyperpolarization observed in control and diabetic arteries remained unaltered even after treatment with 3×10−4 M NG-nitro-L-arginine (L-NOARG), 10−5 M indomethacin or 60 u ml−1 superoxide dismutase. Endothelium-dependent hyperpolarization with 10−6 M A23187, a calcium ionophore, was also decreased in diabetic arteries compared to controls (−8.3±1.4 vs −18.0±1.9 mV). However, endothelium-independent hyperpolarizing responses to 10−6 M pinacidil, a potassium channel opener, were similar in control and diabetic arteries (−20.0±1.4 vs −19.2±1.1 mV). The altered endothelium-dependent hyperpolarizations in diabetic arteries were almost completely prevented by insulin therapy. Endothelium-dependent relaxations by ACh in the presence of 10−4 M L-NOARG and 10−5 M indomethacin in diabetic arteries were also reduced and more transient compared to controls. These data indicate that endothelium-dependent hyperpolarization is reduced by diabetes, and this would, in part, account for the impaired endothelium-dependent relaxations in mesenteric arteries from diabetic rats. PMID:9257918

  16. Endothelium-dependent relaxation of the pig aorta: relationship to stimulation of 86Rb efflux from isolated endothelial cells.

    PubMed Central

    Gordon, J. L.; Martin, W.

    1983-01-01

    Bradykinin, adenosine triphosphate (ATP) and acetylcholine each relaxed histamine-contracted strips of pig aorta in a dose-dependent manner. These relaxations were abolished when the endothelium was removed. Relaxation induced by ATP was mimicked by adenosine diphosphate (ADP) but adenosine monophosphate (AMP) and adenosine were about 120 times less potent. Relaxation induced by acetylcholine was antagonized by atropine in a competitive manner, and carbachol induced the same degree of relaxation as acetylcholine, but was about 10 times less potent. The calcium ionophore, A23187, also induced a dose-dependent relaxation of pig aortic strips provided the endothelium was present, suggesting that a rise in the level of ionized calcium within the endothelial cells is one means by which vascular smooth muscle relaxation can be triggered. Bradykinin, ATP, ADP, AMP, adenosine and A23187 each induced a dose-dependent increase in 86Rb efflux from preloaded pig aortic endothelial cells. The dose-response curves for stimulation of 86Rb efflux and for endothelium-dependent relaxation were similar for each individual compound. ADP was equipotent with ATP, but AMP and adenosine were about 120 times less potent. Neither acetylcholine nor carbachol, in concentrations that induce endothelium-dependent relaxation, had any effect on 86Rb efflux from isolated aortic endothelial cells. Lanthanum, which blocks calcium influx, abolished the increases in 86Rb efflux induced by bradykinin and ATP, and the calcium ionophore A23187 was the most effective stimulant of 86Rb efflux, suggesting that the potassium transport induced by these agents is calcium-activated. It is concluded that endothelial responses to bradykinin and ATP can be assessed by monitoring 86Rb efflux, which probably reflects a calcium-activated efflux of potassium associated with the endothelium-dependent vascular relaxation induced by these agents. This pathway is apparently not involved in endothelial responses to

  17. Visfatin Impairs Endothelium-Dependent Relaxation in Rat and Human Mesenteric Microvessels through Nicotinamide Phosphoribosyltransferase Activity

    PubMed Central

    Angulo, Javier; Villalobos, Laura A.; Cercas, Elena; Leivas, Alejandra; Bermejo, Elena; Carraro, Raffaele; Sánchez-Ferrer, Carlos F.; Peiró, Concepción

    2011-01-01

    Visfatin, also known as extracellular pre–B-cell colony–enhancing factor (PBEF) and nicotinamide phosphoribosyltransferase (Nampt), is an adipocytokine whose circulating levels are enhanced in metabolic disorders, such as type 2 diabetes mellitus and obesity. Circulating visfatin levels have been positively associated with vascular damage and endothelial dysfunction. Here, we investigated the ability of visfatin to directly impair vascular reactivity in mesenteric microvessels from both male Sprague-Dawley rats and patients undergoing non-urgent, non-septic abdominal surgery. The pre-incubation of rat microvessels with visfatin (50 and 100 ng/mL) did not modify the contractile response to noradrenaline (1 pmol/L to 30 µmol/L), as determined using a small vessel myograph. However, visfatin (10 to 100 ng/mL) concentration-dependently impaired the relaxation to acetylcholine (ACh; 100 pmol/L to 3 µmol/L), without interfering with the endothelium-independent relaxation to sodium nitroprusside (1 nmol/L to 3 µmol/L). In both cultured human umbilical vein endothelial cells and rat microvascular preparations, visfatin (50 ng/mL) stimulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, as determined by lucigenin-derived chemiluminiscence. The relaxation to ACh impaired by visfatin was restored by the NADPH oxidase inhibitor apocynin (10 µmol/L). Additionally, the Nampt inhibitor APO866 (10 mmol/L to 10 µmol/L), but not an insulin receptor-blocking antibody, also prevented the stimulation of NADPH oxidase and the relaxation impairment elicited by visfatin. Accordingly, the product of Nampt activity nicotinamide mononucleotide (100 nmol/L to 1 mmol/L) stimulated endothelial NADPH oxidase activity and concentration-dependently impaired ACh-induced vasorelaxation. In human mesenteric microvessels pre-contracted with 35 mmol/L potassium chloride, the endothelium-dependent vasodilation to bradykinin (1 nmol/L to 3 µmol/L) was equally impaired by

  18. Excess L-arginine restores endothelium-dependent relaxation impaired by monocrotaline pyrrole

    SciTech Connect

    Cheng Wei; Oike, Masahiro . E-mail: moike@pharmaco.med.kyushu-u.ac.jp; Hirakawa, Masakazu; Ohnaka, Keizo; Koyama, Tetsuya; Ito, Yushi

    2005-09-15

    The pyrrolizidine alkaloid plant toxin monocrotaline pyrrole (MCTP) causes pulmonary hypertension in experimental animals. The present study aimed to examine the effects of MCTP on the endothelium-dependent relaxation. We constructed an in vitro disease model of pulmonary hypertension by overlaying MCTP-treated bovine pulmonary artery endothelial cells (CPAEs) onto pulmonary artery smooth muscle cell-embedded collagen gel lattice. Acetylcholine (Ach) induced a relaxation of the control CPAEs-overlaid gels that were pre-contracted with noradrenaline, and the relaxation was inhibited by L-NAME, an inhibitor of NO synthase (NOS). In contrast, when MCTP-treated CPAEs were overlaid, the pre-contracted gels did not show a relaxation in response to Ach in the presence of 0.5 mM L-arginine. Expression of endothelial NOS protein, Ach-induced Ca{sup 2+} transients and cellular uptake of L-[{sup 3}H]arginine were significantly smaller in MCTP-treated CPAEs than in control cells, indicating that these changes were responsible for the impaired NO production in MCTP-treated CPAEs. Since cellular uptake of L-[{sup 3}H]arginine linearly increased according to its extracellular concentration, we hypothesized that the excess concentration of extracellular L-arginine might restore NO production in MCTP-treated CPAEs. As expected, in the presence of 10 mM L-arginine, Ach showed a relaxation of the MCTP-treated CPAEs-overlaid gels. These results indicate that the impaired NO production in damaged endothelial cells can be reversed by supplying excess L-arginine.

  19. Diabetes impairs endothelium-dependent relaxation of human penile vascular tissues mediated by NO and EDHF.

    PubMed

    Angulo, Javier; Cuevas, Pedro; Fernández, Argentina; Gabancho, Sonia; Allona, Antonio; Martín-Morales, Antonio; Moncada, Ignacio; Videla, Sebastián; Sáenz de Tejada, Iñigo

    2003-12-26

    Standard treatments for erectile dysfunction (ED) (i.e., PDE5 inhibitors) are less effective in diabetic patients for unknown reasons. Endothelium-dependent relaxation (EDR) of human corpus cavernosum (HCC) depends on nitric oxide (NO), while in human penile resistance arteries (HPRA) endothelium-derived hyperpolarizing factor (EDHF) and NO participate. Here we show that diabetes significantly reduced EDR induced by acetylcholine (ACh) in HCC and HPRA. Relaxation attributed to EDHF was also impaired in HPRA from diabetic patients. The PDE5 inhibitor, sildenafil (10nM), reversed diabetes-induced endothelial dysfunction in HCC, but not in HPRA. Calcium dobesilate (DOBE; 10 microM) fully reversed diabetes-induced endothelial dysfunction in HPRA by specifically potentiating the EDHF-mediated component of EDR. Impairment by diabetes of NO and EDHF-dependent responses precluded the complete recovery of endothelial function in HPRA by sildenafil. This could explain the poor clinical response to PDE5 inhibitors of diabetic men with ED and suggests that a pharmacological approach that combines enhancement of NO/cGMP and EDHF pathways could be necessary to treat ED in many diabetic men.

  20. Vascular effects of Siberian ginseng (Eleutherococcus senticosus): endothelium-dependent NO- and EDHF-mediated relaxation depending on vessel size.

    PubMed

    Kwan, Chiu-Yin; Zhang, Wen-Bo; Sim, Si-Mui; Deyama, Takeshi; Nishibe, Sansei

    2004-05-01

    Siberian ginseng (SG) has been widely and historically consumed as a health food product for the improvement of self well-being, but whether vascular relaxation may contribute to such a therapeutic health effect has not been studied. We therefore investigated the vasorelaxant effect of the aqueous extract of the roots of SG (Eleutherococcus senticosus Maxim) using several in vitro vascular rings prepared from dog carotid artery, rat aorta and rat mesenteric artery. SG extract (0.04-0.8 mg/ml) caused concentration-dependent relaxation in dog carotid arterial rings pre-contracted with 100 microM phenylephrine (PE), and the relaxation was primarily endothelium-dependent. Treatment with 100 microM L-NOARG (a nitric oxide synthase inhibitor) either prevented or totally reverted SG-induced relaxation, suggesting that the endothelium-dependent relaxation was mediated by NO. Similar endothelium-dependent vascular relaxant responses were also obtained with rat aortic and mesenteric arterial rings, except that it occurred over a relatively higher concentration range of SG (0.5-2.0 mg/ml). When tested in the presence of 300 microM L-NAME, the vasorelaxant effect of SG was inhibited totally in rat aorta but only partially in rat mesenteric artery. The relaxation to SG that was insensitive to L-NAME in rat mesenteric arterial rings was eliminated when the rings (both proximal and distal ends) were pre-treated with a combination of 300 microM L-NAME and 15 mM KCl indicating the involvement of endothelium-derived hyperpolarizing factor (EDHF). This vasorelaxant response of the SG extract was inhibited partially by atropine (1 microM), completely by TEA (5 mM), but not by indomethacin (1 microM) or propranolol (10 microM). SG up to 2 mg/ml had no effect on KCl-induced contraction in any of the vascular rings studied. When compared with carbachol-induced (CCh) relaxation, SG resembles CCh in that the sensitivity to L-NAME inhibition is dependent on vascular size, i.e. aorta

  1. Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta.

    PubMed Central

    Bossaller, C; Habib, G B; Yamamoto, H; Williams, C; Wells, S; Henry, P D

    1987-01-01

    The dependence of vascular relaxation on an intact endothelium and the relationship between relaxation and cyclic GMP accumulation were determined in coronary arteries isolated from cardiac transplantation patients with or without coronary atherosclerosis. In nonatherosclerotic arteries, the endothelium-dependent agent acetylcholine produced concentration-related relaxations. In atherosclerotic arteries, endothelium-dependent relaxations were abolished with acetylcholine, partly suppressed with substance P and histamine, and completely preserved with the ionophore A23187. In these arteries, the endothelium-independent agent nitroglycerin remained fully active. Accumulation of cyclic GMP in atherosclerotic strips was suppressed with acetylcholine but unattenuated with A23187 and nitroglycerin. In aortas from rabbits with diet-induced atherosclerosis, there was likewise an impaired cholinergic relaxation and cyclic GMP accumulation in the presence of preserved responses to A23187 and nitroglycerin. The results demonstrate that impaired cholinergic responses in atherosclerotic arteries reflect a muscarinic defect and not an inability of endothelium to release endothelial factor or smooth muscle to respond to it. PMID:2432088

  2. Effect of prolonged incubation with copper on endothelium-dependent relaxation in rat isolated aorta

    PubMed Central

    Chiarugi, Alberto; Pitari, Giovanni Mario; Costa, Rosa; Ferrante, Margherita; Villari, Loredana; Amico-Roxas, Matilde; Godfraind, Théophile; Bianchi, Alfredo; Salomone, Salvatore

    2002-01-01

    We investigated the effects of prolonged exposure to copper (Cu2+) on vascular functioning of isolated rat aorta. Aortic rings were exposed to CuSO4 (3–24 h) in Dulbecco's modified Eagle medium with or without 10% foetal bovine serum (FBS) and then challenged with vasoconstrictors or vasodilators in the absence of Cu2+. Exposure to 2 μM Cu2+ in the absence of FBS did not modify the response to phenylephrine (PE) or acetylcholine (ACh) in aortic rings incubated for 24 h. Identical exposure in the presence of FBS increased the contractile response to 1 μM PE by 30% (P<0.05) and impaired the relaxant response to 3 μM ACh or 1 μM A23187 (ACh, from 65.7±7.1 to 6.2±1.1%, n=8; A23187, from 74.6±8.2 to 12.0±0.8%, n=6; P<0.01 for both). Cu2+ exposure did not affect the relaxant response to NO-donors. Impairment of vasorelaxation appeared 3 h after incubation with 2 μM Cu2+ and required 12 h to attain a steady state. Vasorelaxation to ACh was partially restored by 1 mM tiron (intracellular scavenger of superoxide ions; maximum relaxation 34.2±6.4%, n=10, P<0.01 vs Cu2+ alone), whereas catalase, superoxide dismutase or cycloheximide were ineffective. Twenty-four hour-exposure to 2 μM Cu2+ did not affect endothelium integrity or eNOS expression, and increased the Cu content in arterial rings from 6.8±1.1 to 18.9±2.9 ng mg−1 wet weight, n=8; P<0.01. Our results show that, in the presence of FBS, prolonged exposure to submicromolar concentrations of Cu2+ impaired endothelium-dependent vasorelaxation in aortic rings, probably through an intracellular generation of superoxide ions. PMID:12163352

  3. Endothelium-Dependent Relaxation and Angiotensin II Sensitivity in Experimental Preeclampsia

    PubMed Central

    van der Graaf, Anne Marijn; Wiegman, Marjon J.; Plösch, Torsten; Zeeman, Gerda G.; van Buiten, Azuwerus; Henning, Robert H.; Buikema, Hendrik; Faas, Marijke M.

    2013-01-01

    Objective We investigated endothelial dysfunction and the role of angiotensin (Ang)-II type I (AT1-R) and type II (AT2-R) receptor in the changes in the Ang-II sensitivity in experimental preeclampsia in the rat. Methods Aortic rings were isolated from low dose lipopolysaccharide (LPS) infused pregnant rats (experimental preeclampsia; n=9), saline-infused pregnant rats (n=8), and saline (n=8) and LPS (n=8) infused non-pregnant rats. Endothelium-dependent acetylcholine--mediated relaxation was studied in phenylephrine-preconstricted aortic rings in the presence of vehicle, NG-nitro-L-arginine methyl ester and/or indomethacin. To evaluate the role for AT1-R and AT2-R in Ang-II sensitivity, full concentration response curves were obtained for Ang-II in the presence of losartan or PD123319. mRNA expression of the AT1-R and AT2-R, eNOS and iNOS, COX1 and COX2 in aorta were evaluated using real-time RT-PCR. Results The role of vasodilator prostaglandins in the aorta was increased and the role of endothelium-derived hyperpolarizing factor and response of the AT1-R and AT2-R to Ang-II was decreased in pregnant saline infused rats as compared with non-pregnant rats. These changes were not observed during preeclampsia. Conclusion Pregnancy induced adaptations in endothelial function, which were not observed in the rat model for preeclampsia. This role of lack of pregnancy induced endothelial adaptation in the pathophysiology of experimental preeclampsia needs further investigation. PMID:24223202

  4. Natural course of the impairment of endothelium-dependent relaxations after balloon endothelium removal in porcine coronary arteries. Possible dysfunction of a pertussis toxin-sensitive G protein.

    PubMed

    Shimokawa, H; Flavahan, N A; Vanhoutte, P M

    1989-09-01

    The purposes of the present study were to examine the natural course of the impairment of endothelium-dependent relaxations during a regeneration and tissue repair process after balloon endothelium removal and to elucidate the cellular mechanism(s) underlying it. Twenty-three male Yorkshire pigs underwent balloon endothelium removal along the proximal portion of either the left anterior descending or circumflex coronary artery and were then maintained on a regular chow for 4, 8, 16, or 24 weeks. Endothelium-dependent responses were examined in vitro in rings taken from the control and previously denuded arteries studied in parallel. Morphometric analysis revealed that intimal thickening developed only at the previously denuded area. In the previously denuded arteries with regenerated endothelium, the endothelium-dependent relaxations to UK 14304 (a selective alpha 2-adrenergic agonist), serotonin, and aggregating platelets were impaired 4 weeks after endothelium removal and remained so throughout the study. The endothelium-dependent relaxations to thrombin and adenosine diphosphate became depressed 8 weeks after endothelium removal and those to bradykinin became depressed 16 weeks after endothelium removal, while those to the calcium ionophore A23187 were maintained throughout the study. Endothelium-dependent relaxations to all vasoactive agents were unaltered in the control arteries. In the control arteries, pertussis toxin, an inhibitor of certain G proteins, markedly inhibited the endothelium-dependent relaxations to UK 14304 and serotonin and partially inhibited those to thrombin and aggregating platelets. The responses inhibited by the toxin in control arteries were significantly reduced in the reduced in the previously denuded arteries with regenerated endothelium. The inhibitory effect of pertussis toxin was markedly reduced in those arteries with regenerated endothelium. In quiescent rings, the presence of normal endothelium inhibited the contractions

  5. Effects of calcium dobesilate on the synthesis of endothelium-dependent relaxing factors in rabbit isolated aorta

    PubMed Central

    Ruiz, E; Lorente, R; Tejerina, T

    1997-01-01

    Some cardiovascular disturbances which occur in diabetics are a consequence of alterations in vascular contractility as well as in endothelium-dependent relaxation. Calcium dobesilate (DOBE) is a drug used in diabetic retinopathy and its mechanism of action is not yet understood. The aim of this study was to investigate the effects of DOBE on synthesis and release of endothelium-dependent relaxing factor (EDRF) and endothelium-dependent hyperpolarizing factor (EDHF) in rabbit isolated aorta. Endothelium-dependent relaxation induced by acetylcholine (ACh) (10−8–10−5 M) increased in the presence of DOBE 10−5 M only when vascular endothelium was kept intact. NG-nitro-L-arginine methyl ester (L-NAME; 10−8–10−4 M progressively decreased the enhancing effect of DOBE on endothelium-dependent relaxation whereas it was progressively increased by L-Arg. DOBE 10−5 M increased in a non-significant manner endothelium-dependent relaxation induced by ACh when the arteries were incubated with both L-NAME 10−4 M and indomethacin 10−6 M. DOBE (10−6 M and 10−5 M) was able to scavenge superoxide anion radicals generated by the hypoxanthine/xanthine oxidase reaction. These results provide evidence that DOBE is able to affect the vascular disorders associated with diabetes mellitus since it enhances the synthesis of endothelium-dependent relaxing factors. PMID:9208138

  6. Endothelium-dependent and-independent relaxation induced by resveratrol in rat superior mesenteric arteries

    PubMed Central

    Chen, Yulong; Xu, Cangbao; Wei, Yahui; Zhang, Yaping; Cao, Ailan

    2016-01-01

    Resveratrol (Res) is a specific agonist of sirtuin 1, and has many cardioprotective effects. Although Res is able to relax various vascular beds, its pharmacological properties in rat superior mesenteric arteries and the underlying mechanism are not well clarified. The aim of present study was to investigate the vasorelaxant effects of Res on rat superior mesenteric arteries and the mechanisms involved. The isometric tension of rat superior mesenteric arterial rings was recorded in vitro using myography. It was found that Res concentration-dependently relaxed endothelium-intact superior mesenteric artery rings pre-contracted by phenylephrine hydrochloride (Emax, 97.66±0.79%; pD2, 4.30±0.14) or KCl (Emax, 101.3±0.6%; pD2, 4.12±0.03). The vasorelaxant effect of Res on the superior mesenteric artery rings was partially endothelium-dependent. NG-nitro-L-arginine methyl ester (100 µM) significantly inhibited the Res-induced vasorelaxant effect. However, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (10 µM) and indomethacin (5 µM) each had no effect on the Res-induced vasorelaxation. In artery rings without endothelium, the vasorelaxation induced by Res was attenuated by 4-aminopyridine (100 µM) and glibenclamide (10 µM). However, barium chloride dehydrate (10 µM) and tetraethylammonium chloride (1 mM) did not affect the vasorelaxation induced by Res. Moreover, Res also inhibited the contraction induced by an increase in external calcium concentration in Ca2+-free medium plus KCl (60 mM). These results suggest that Res induces relaxation in superior mesenteric arterial rings through an endothelium-dependent pathway, involving nitric oxide release, and also through an endothelium-independent pathway, with opening of voltage-dependent K+ channels and ATP-sensitive K+ channels and blockade of extracellular Ca2+ influx. PMID:27698719

  7. Irisin relaxes mouse mesenteric arteries through endothelium-dependent and endothelium-independent mechanisms.

    PubMed

    Jiang, Miao; Wan, Fangzhu; Wang, Fang; Wu, Qi

    2015-12-25

    Irisin, a newly discovered myokine, has been shown to produce modest weight loss and improve glucose intolerance in mice. The purpose of this study was to investigate the effects of irisin on vascular activity and the mechanisms involved. Experiments were performed on mouse mesenteric arteries. We demonstrated that irisin induced relaxation in mesenteric arteries with or without endothelium in a concentration-dependent manner. It was further demonstrated that the irisin-induced vasorelaxation effects on endothelium-intact mesenteric arteries were reduced by pretreatment with Nω-nitro-L-arginine methyl ester (L-NAME) or 1H-[1, 2, 4] oxadizolo [4, 3-a] quinoxalin-1-one (ODQ). However, pretreatment with indomethacin (INDO), a nonselective cyclooxygenase inhibitor did not modulate irisin-induced relaxation. In addition, the contraction due to extracellular Ca(2+) influx and intracellular Ca(2+) release was also inhibited by irisin. In summary, these results suggested that the endothelium-dependent relaxation of irisin is mediated by the nitric oxide (NO)-guanosine 3', 5'-cyclic phosphate (cGMP)-dependent pathway but not the prostaglandin I2 (PGI2)-cyclic adenosine monophosphate (cAMP)-dependent mechanism. Endothelium-independent relaxation may be depend on inhibiting Ca(2+) influx through blocking VDCCs and intracellular Ca(2+) release through both IP3R and RyR channels.

  8. Endothelium-dependent and -independent relaxation of rat aorta induced by extract of Schizophyllum commune.

    PubMed

    Chen, Haiyun; Li, Sujuan; Wang, Peng; Yan, Saimei; Hu, Lin; Pan, Xiaoxia; Yang, Cui; Leung, George Pakheng

    2014-09-25

    Schizophyllum commune (SC) is widely consumed by Chinese, especially in southern part of China. The aim of the present study was to assess the extract of SC on vascular tone and the mechanisms involved. Experiments were performed on aorta of 18-week-old male Sprague-Dawley rats. Dried SC was extracted with 50% ethanol, 90% ethanol and deionized water, respectively. The effects of SC on the isometric tension of rat aortic rings were measured. Protein expression for the endothelial nitric oxide synthase (eNOS) was also determined in the primarily cultured rat aortic arterial endothelial cells (RAECs). The results showed that the water extract of SC induced a marked relaxation in aortic rings with or without endothelium. After the pretreatments of N(ω)-nitro-l-arginine methyl ester, indomethacin, RP-cAMP, and methylene blue, the SC-induced relaxation was significantly decreased. In addition, the contraction due to Ca(2+) influx and intracellular Ca(2+) release was also inhibited by SC. Furthermore, expression of the eNOS protein was significantly elevated in RAECs after treatment of SC. In conclusion, the water extract of SC induces an endothelium-dependent and -independent relaxation in rat aorta. The relaxing effect of SC involves the modulation of NO-cGMP-dependent pathways, PGI2-cAMP-depedent pathways, Ca(2+) influx though calcium channels and intracellular Ca(2+) release. Copyright © 2014 Elsevier GmbH. All rights reserved.

  9. [HYDROGEN SULFIDE DONOR, NAHS, RECOVERS CONSTITUTIVE NO SYNTHESIS AND ENDOTHELIUM-DEPENDENT RELAXATION OF ISOLATED AORTA IN OLD RATS].

    PubMed

    Drachuk, K O; Kotsjuruba, A V; Sagach, V F

    2015-01-01

    The objective of this study was to show the effect of H₂S donor, NaHS on the endothelium-dependent vasorelaxation, free radical state and cNOS uncoupling in old rats. In the aorta of old rats a combined oxidative and nitrosative stress develops that leads to cNOS uncoupling and decreased constitutive synthesis of the NO. That biochemical changes correlate with lowering of the endothelium-dependent relaxation of aortic smooth muscles (7.5 ± 1.4%, compared with 64.9 ± 3.5% in adults). It was found that, due to the combined inhibition of oxidative and nitrosative stress, NaHS restores constitutive de novo synthesis of NO by restoring cNOS coupling. Additionally, NaHS improves endothelium-dependent vasorelaxation by increasing (by 6.5 times) Ach-induced relaxation of aortic smooth muscles.

  10. Evidence that A2 purinoceptors are involved in endothelium-dependent relaxation of the rat thoracic aorta.

    PubMed Central

    Rose'Meyer, R. B.; Hope, W.

    1990-01-01

    1. The effect of adenosine and some adenosine analogues on the isolated thoracic aorta from rats was compared with the effect of adenosine 5'-triphosphate (ATP) and adenosine 5'-diphosphate (ADP). 2. Both ATP and adenosine analogues caused relaxation of the noradrenaline (30 nM)-contracted thoracic aorta. 3. The order of potency for adenosine analogues was 5'-(N-ethyl) carboxamidoadenosine (NECA) greater than L-N6-phenylisopropyladenosine (L-PIA), adenosine 5'-monophosphate (AMP), adenosine indicating the presence of adenosine A2 receptors. 4. Removal of the endothelium or prior treatment with haemoglobin (10 microM) attenuated relaxant responses to both ATP and NECA, attenuation being greater for ATP than NECA. 5. 8-Phenyltheophylline (10 microM) reduced relaxant responses to NECA but not to ATP in the intact tissue. 6. These results provide evidence that there are two components to relaxation of the rat thoracic aorta induced by purinoceptor agonists. The first is an endothelium-dependent mechanism involving release of endothelium-derived relaxant factor (EDRF) and the second is due to a direct effect on smooth muscle. PMID:2390681

  11. Hypertension and impairment of endothelium-dependent relaxation of arteries from spontaneously hypertensive and L-NAME-treated Wistar rats.

    PubMed

    Sekiguchi, F; Miyake, Y; Hirakawa, A; Nakahira, T; Yamaoka, M; Shimamura, K; Yamamoto, K; Sunano, S

    2001-04-01

    Effects of chronic treatment of normotensive Wistar rats with N(omega)-nitro-L-arginine methyl ester (L-NAME) on blood pressure and on endothelium-dependent relaxation of the aorta, carotid and iliac arteries were studied. The endothelium-dependent relaxation was compared in arteries from normotensive Wistar Kyoto rats (WKY) and genetically hypertensive rats (stroke-prone spontaneously hypertensive rats, SHRSP). Chronic treatment of normotensive Wistar rats with L-NAME caused an elevation of blood pressure. The elevated blood pressure at 15 weeks of age was significantly higher in these animals than that of untreated Wistar rats, but lower than that of SHRSP. Endothelium-dependent relaxation of the arteries induced by acetylcholine (ACh) was almost abolished by chronic treatment with L-NAME. The remaining small relaxation in arteries from L-NAME-treated rats was completely inhibited by application of L-NAME (10(-4) M). In such preparations, higher concentrations of ACh induced a contraction, which was abolished by removal of the endothelium or by an application of indomethacin (10(-5) M). Endothelium-independent relaxation induced by sodium nitroprusside was similar between preparations from untreated and L-NAME-treated Wistar rats. Endothelium-dependent relaxation was significantly impaired in preparations from SHRSP, when compared with that in those from WKY. However, the impairment was less prominent in preparations from SHRSP than in those from L-NAME-treated rats. These results suggest that the impairment of endothelium-dependent relaxation in the arteries from L-NAME-treated rats is not due to the elevated blood pressure resulting from the chronic treatment, and that impairment of NO synthesis by the endothelium does not play a major role in the initiation of hypertension in SHRSP.

  12. Endothelium-Dependent Nitric Oxide and Hyperpolarization-Mediated Venous Relaxation Pathways in Rat Inferior Vena cava

    PubMed Central

    Raffetto, Joseph D.; Yu, Peng; Reslan, Ossama M.; Xia, Yin; Khalil, Raouf A.

    2011-01-01

    -NAME and indomethacin suggesting that any Ach-induced EDHF is blocked in the presence of high KCl depolarizing solution, which does not favor outward movement of K+ ion and membrane hyperpolarization. Cromakalim, activator of KATP, caused significant IVC relaxation when applied alone or on top of maximal Ach-induced relaxation, suggesting that the Ach response may not involve KATP. Ach-induced relaxation was not inhibited by glibenclamide, 4-AP or apamin, suggesting little role of KATP, Kv or SKCa, respectively. In contrast, iberiotoxin significantly inhibited Ach-induced relaxation, suggesting a role of BKCa. Conclusions Thus endothelium-dependent venous relaxation plays a major role in the control of venous function. In addition to NO, an EDHF pathway involving BKCa may play a role in endothelium-dependent venous relaxation. PMID:22209615

  13. Superoxide dismutase reduces the impairment of endothelium-dependent relaxation in the spontaneously hypertensive rat aorta.

    PubMed

    Sekiguchi, Fumiko; Yanamoto, Aiko; Sunano, Satoru

    2004-04-01

    The involvement of the superoxide anion in endothelium-dependent relaxation (EDR) was examined in noradrenaline-contracted aortic smooth muscle preparations isolated from normotensive Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Acetylcholine (ACh, 10(-9)-10(-5) M) induced EDR in both WKY and SHRSP preparations in a concentration-dependent manner, but with a significantly smaller amplitude in those from SHRSP than in those from WKY. The ACh-induced EDR was inhibited by N(omega)-nitro-L-arginine (L-NOARG), in a concentration-dependent manner, both in WKY and SHRSP. The EDR produced in WKY in the presence of 3 x 10(-6) M L-NOARG was similar in magnitude to that produced in SHRSP in the absence of L-NOARG. Superoxide dismutase (SOD, 300 units/ml) increased the amplitude of EDR in SHRSP but not in WKY, with no alteration of the threshold or of the maximal amplitude. The maximal amplitude of EDR produced in SHRSP in the presence of SOD was still smaller than that in WKY. In WKY, a possible involvement of superoxide in the EDR was examined in aortae whose EDR was partially inhibited by treatment with a subthreshold concentration (3 x 10 (-6) M) of L-NOARG. In the L-NOARG-conditioned aorta, the reduced EDR was partially but significantly recovered by SOD. These results suggest that the impaired EDR in aortae of SHRSP may be causally related to a higher production of superoxide. The L-NOARG-induced inhibition of EDR in WKY may be produced, in part, by the reduction of effective NO due to its destruction by superoxide.

  14. Role of AMP-activated Protein Kinase in NO- and EDHF-mediated Endothelium-dependent Relaxations to Red Wine Polyphenols.

    PubMed

    Kane, Modou Oumy; Sene, Mbaye; Anselm, Eric; Dal, Stéphanie; Schini-Kerth, Valérie B; Augier, Cyril

    2015-01-01

    Several epidemiological studies have shown that regular consumption of moderate amounts of wine, in particular red wine, is associated with a decreased total mortality due, in part, to a reduced risk of cardiovascular diseases. The protective effect has been attributable to polyphenols, which are potent vasodilators and have anti-thrombotic properties. Polyphenols have been shown to induce pronounced endothelium-dependent relaxations of arteries by causing the redox-sensitive PI3-kinase-dependent formation of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). The aim of the present study was to determine the role of the AMP-activated protein kinase (AMPK) in the red wine polyphenols (RWPs)-induced endothelial formation of NO and EDHF. Vascular reactivity was assessed in organ chambers. Cultured porcine coronary artery endothelial cells porcine coronary artery segements were used to study the phosphorylation level of endothelial NO synthase (eNOS) at serine 1177, and AMPK at the Threonine 172 by Western blot analysis and immunohistochemical staining. RWPs caused endothelium-dependent relaxations in rings from rat aorta and mesenteric artery, and in those from porcine coronary artery. NO-mediated relaxations to RWPs as assessed in the presence of indomethacin and charybdotoxin plus apamin, were inhibited by compound C (an inhibitor of AMPK). Compound C also reduced EDHF-mediated relaxations as assessed in the presence of indomethacin and N(G)-nitro L-arginine. In contrast, compound C did not affect endothelium-dependent relaxations to acetylcholine and those to sodium nitroprusside. Moreover, RWPs induced the phosphorylation of AMPK at threonine 172 and eNOS at serine 1177 in endothelial cells; these responses were inhibited by compound C. The present findings indicate that RWPs cause both NO and EDHF-mediated relaxations in several types of isolated arteries and that these effects are dependent on the activation of the AMP-activated protein

  15. Exercise training-induced adaptations in mediators of sustained endothelium-dependent coronary artery relaxation in a porcine model of ischemic heart disease

    PubMed Central

    Heaps, Cristine L.; Robles, Juan Carlos; Sarin, Vandana; Mattox, Mildred L.; Parker, Janet L.

    2014-01-01

    Objective Test the hypothesis that exercise training enhances sustained relaxation to persistent endothelium-dependent vasodilator exposure via increased nitric oxide contribution in small coronary arteries of control and ischemic hearts. Methods Yucatan swine were designated to a control group or a group in which an ameroid constrictor was placed around the proximal LCX. Subsequently, pigs from both groups were assigned to exercise (5 days/week; 16 weeks) or sedentary regimens. Coronary arteries (~100–350 μm) were isolated from control pigs and from both nonoccluded and collateral-dependent regions of chronically-occluded hearts. Results In arteries from control pigs, training significantly enhanced relaxation responses to increasing concentrations of bradykinin (10−10 to 10−7 M) and sustained relaxation to a single bradykinin concentration (30 nM), which were abolished by NOS inhibition. Training also significantly prolonged bradykinin-mediated relaxation in collateral-dependent arteries of occluded pigs, which was associated with more persistent increases in endothelial cellular Ca2+ levels, and reversed with NOS inhibition. Protein levels for eNOS and p-eNOS-(Ser1179), but not caveolin-1, Hsp90, or Akt, were significantly increased with occlusion, independent of training state. Conclusions Exercise training enhances sustained relaxation to endothelium-dependent agonist stimulation in small arteries of control and ischemic hearts by enhanced nitric oxide contribution and endothelial Ca2+ responses. PMID:24447072

  16. Palm oil tocotrienol fractions restore endothelium dependent relaxation in aortic rings of streptozotocin-induced diabetic and spontaneously hypertensive rats.

    PubMed

    Muharis, Syed Putra; Top, Abdul Gapor Md; Murugan, Dharmani; Mustafa, Mohd Rais

    2010-03-01

    Diabetes and hypertension are closely associated with impaired endothelial function. Studies have demonstrated that regular consumption of edible palm oil may reverse endothelial dysfunction. The present study investigates the effect of palm oil fractions: tocotrienol rich fraction (TRF), alpha-tocopherol and refined palm olein (vitamin E-free fraction) on the vascular relaxation responses in the aortic rings of streptozotocin-induced diabetic and spontaneously hypertensive rats (SHR). We hypothesize that the TRF and alpha-tocopherol fractions are able to improve endothelial function in both diabetic and hypertensive rat aortic tissue. A 1,1-diphenyl picryl hydrazyl assay was performed on the various palm oil fractions to evaluate their antioxidant activities. Endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) relaxations were examined on streptozotocin-induced diabetic and SHR rat aorta following preincubation with the different fractions. In 1-diphenyl picryl hydrazyl antioxidant assay, TRF and alpha-tocopherol fractions exhibited a similar degree of activity while palm olein exhibited poor activity. TRF and alpha-tocopherol significantly improved acetylcholine-induced relaxations in both diabetic (TRF, 88.5% +/- 4.5%; alpha-tocopherol, 87.4% +/- 3.4%; vehicle, 65.0 +/- 1.6%) and SHR aorta (TRF, 72.1% +/- 7.9%; alpha-tocopherol, 69.8% +/- 4.0%, vehicle, 51.1% +/- 4.7%), while palm olein exhibited no observable effect. These results suggest that TRF and alpha-tocopherol fractions possess potent antioxidant activities and provide further support to the cardiovascular protective effects of palm oil vitamin E. TRF and alpha-tocopherol may potentially improve vascular endothelial function in diabetes and hypertension by their sparing effect on endothelium derived nitric oxide bioavailability.

  17. Grape juice causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of eNOS.

    PubMed

    Anselm, Eric; Chataigneau, Marta; Ndiaye, Mamadou; Chataigneau, Thierry; Schini-Kerth, Valérie B

    2007-01-15

    An enhanced endothelial formation of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), is thought to contribute to the protective effect of moderate consumption of red wine on coronary diseases. The present study has characterized endothelium-dependent relaxations to Concord grape juice (CGJ), a non-alcoholic rich source of grape-derived polyphenols, in the coronary artery. Porcine coronary artery rings were suspended in organ chambers for the measurement of changes in isometric tension in the presence of indomethacin. NO formation was assessed by electron spin resonance spectroscopy, and the phosphorylation of Src, Akt and endothelial NO synthase (eNOS) by Western blot analysis in cultured endothelial cells. Endothelium-dependent relaxations to CGJ were slightly but significantly reduced by L-NA, not affected by charybdotoxin (CTX) plus apamin (APA, two inhibitors of EDHF-mediated responses) whereas the combination of L-NA, CTX plus APA reduced maximal relaxation to about 50%. In the presence of CTX plus APA, relaxations to CGJ were markedly reduced by the membrane permeant mimetic of superoxide dismutase (SOD), MnTMPyP, the membrane permeant analogue of catalase polyethyleneglycol-catalase (PEG-catalase), PP2, an inhibitor of Src kinase, and by wortmannin, an inhibitor of the PI3-kinase. CGJ stimulated the formation of reactive oxygen species and the N(omega)-nitro-L-arginine-, PP2- and wortmannin-sensitive formation of NO in endothelial cells. The formation of NO was associated with a redox-sensitive and time-dependent phosphorylation of Src, Akt and eNOS. CGJ induces endothelium-dependent relaxations of coronary arteries, which involve a NO-mediated component and also, to a minor extent, an EDHF-mediated component. In addition, CGJ-induced NO formation is due to the redox-sensitive activation of Src kinase with the subsequent PI3-kinase/Akt-dependent phosphorylation of eNOS.

  18. Endothelium-dependent relaxation in pulmonary arteries of L-NAME-treated Wistar and stroke-prone spontaneously hypertensive rats.

    PubMed

    Sekiguchi, Fumiko; Yamamoto, Kazuo; Matsuda, Kyoko; Kawata, Kyoko; Negishi, Maki; Shinomiya, Kazuaki; Shimamur, Keiichi; Sunano, Satoru

    2002-10-01

    To evaluate whether the elevated blood pressure induced by chronic treatment with N(omega)-nitro-L-arginine methyl ester (L-NAME) contributes to an impairment of endothelium-dependent relaxation (EDR), the effects of chronic treatment of Wistar rats with L-NAME on systolic blood pressure, pulmonary arterial blood pressure and EDR of the pulmonary arteries were studied and compared with those of stroke-prone spontaneously hypertensive rats (SHRSP). While the systolic blood pressure (SBP) of Wistar rats was increased above that of controls by chronic treatment with L-NAME, it was still significantly lower than that of SHRSP. Chronic treatment with L-NAME did not affect pulmonary arterial blood pressure. On the other hand, the pulmonary arterial blood pressure of SHRSP was slightly but significantly higher than that of the control normotensive Wistar Kyoto rats (WKY). EDR in response to acetylcholine in the pulmonary artery of L-NAME-treated rats was significantly smaller than that in control Wistar rats. The EDR markedly increased in the presence of L-arginine and completely disappeared in the presence of N(omega)-nitro-L-arginine. Indomethacin hardly affected EDR. In preparations from SHRSP, the EDR was not different from that in those from WKY. Relaxation induced by sodium nitroprusside was identical in all preparations. Elevation of SBP and the impairment of EDR observed in L-NAME-treated rats recovered two weeks following cessation of treatment. These results suggest that the impaired EDR in the pulmonary artery of L-NAME-treated rats is not due to an L-NAME-induced increase in blood pressure but due to the inhibition of nitric oxide synthase by the drug remaining in the endothelium.

  19. Endothelium-Dependent Relaxation Effect of Apocynum venetum Leaf Extract via Src/PI3K/Akt Signalling Pathway

    PubMed Central

    Lau, Yeh Siang; Ling, Wei Chih; Murugan, Dharmani; Kwan, Chiu Yin; Mustafa, Mohd Rais

    2015-01-01

    Botanical herbs are consumed globally not only as an essential diet but also as medicines or as functional/recreational food supplements. The extract of the Apocynum venetum leaves (AVLE), also known as Luobuma, exerts its antihypertensive effect via dilating the blood vessels in an endothelium- and concentration-dependent manner with optimal effect seen at as low as 10 µg/mL. A commercial Luoboma “antihypertensive tea” is available commercially in the western province of China. The present study seeks to investigate the underlying cellular mechanisms of the nitric oxide (NO)-releasing property of AVLE in rat aortas and human umbilical vein endothelial cells (HUVECs). Endothelium-dependent relaxation induced by AVLE was assessed in organ chambers in the presence or absence of polyethyleneglycol catalase (PP2, 20 µM; inhibitor of Src kinase), wortmannin (30 nM) and LY294002 (20 µM; PI3 (phosphatidylinositol3)-Kinase inhibitor), NG-nitro-l-arginine (L-NAME, 100 µM; endothelial NO synthase inhibitor (eNOS)) and ODQ (1 µM; soluble guanylyl cyclase inhibitor). Total nitrite and nitrate (NOx) level and protein expression of p-Akt and p-eNOS were measured. AVLE-induced endothelium-dependent relaxation was reduced by PP2, wortmannin and LY294002 and abolished by L-NAME and ODQ. AVLE significantly increased total NOx level in rat aortas and in HUVECs compared to control. It also instigated phosphorylation of Akt and eNOS in cultured HUVECs in a concentration-dependent manner and this was markedly suppressed by PP2, wortmannin and LY294002. AVLE also inhibited superoxide generated from both NADPH oxidase and xanthine/xanthine oxidase system. Taken together, AVLE causes endothelium-dependent NO mediated relaxations of rat aortas through Src/PI3K/Akt dependent NO signalling pathway and possesses superoxide scavenging activity. PMID:26133970

  20. Effect of chronic lithium administration on endothelium-dependent relaxation of rat corpus cavernosum: the role of nitric oxide and cyclooxygenase pathways.

    PubMed

    Sadeghipour, Hamed; Ghasemi, Mehdi; Nobakht, Maliheh; Ebrahimi, Farzad; Dehpour, Ahmad Reza

    2007-01-01

    To verify the effect of chronic lithium administration on the endothelium-dependent relaxation of rat corpus cavernosum, as lithium is a major drug for treating bipolar disorder and some studies showed that lithium might cause erectile dysfunction in such patients, by a mechanism as yet unknown. LiCl (600 mg/L) was dissolved in drinking water and Sprague-Dawley rats received the solution for 30 days; control rats received tap water. After 30 days corporeal strips were prepared from both groups, mounted under tension in oxygenated organ baths, and pre-contracted with phenylephrine (7.5 microm). After equilibration, the strips were relaxed by acetylcholine (10 nm to 1 mm) in the presence or absence of indomethacin (a cyclooxygenase inhibitor; 20 microm). Furthermore, the relaxant responses to sodium nitroprusside (1 nm to 1 mm), a nitric oxide (NO) donor, were investigated in both groups. NADPH-diaphorase histochemistry was used to identify NO synthase within cavernosal tissue strips of both groups. The acetylcholine-dependent relaxation was significantly lower in lithium-treated rats than in controls. Although indomethacin decreased significantly the relaxant responses to acetylcholine in controls, it increased the relaxant responses in lithium-treated rats. NADPH-diaphorase staining was greater in the chronic lithium-treated than in control preparations. Sodium nitroprusside produced similar relaxation in both groups. Chronic lithium administration can impair the endothelium-dependent relaxation of rat corpus cavernosum; NO availability might decrease after lithium administration and the cyclooxygenase pathways might have a role in this effect.

  1. Effects of trientine, a metal chelator, on defective endothelium-dependent relaxation in the mesenteric vasculature of diabetic rats.

    PubMed

    Inkster, Melanie E; Cotter, Mary A; Cameron, Norman E

    2002-10-01

    Diabetes mellitus compromises endothelium-dependent relaxation of blood vessels. This has been linked to the generation of reactive oxygen species (ROS), which neutralise nitric oxide (NO) and interfere with vasodilator function. Experiments using chelators have emphasised the importance of ROS produced by transition metal catalysed reactions. However, particularly for the small arteries and arterioles that control microcirculatory blood flow, NO is not the only endothelium-derived mediator; endothelium-derived hyperpolarizing factor (EDHF) has a major role. EDHF-mediated vasodilation is severely curtailed by diabetes; however, little information exists on the underlying pathophysiology. Deficits in the EDHF system, alone or in combination with the NO system, are crucial for the development of diabetic microvascular complications. To further elucidate the mechanisms involved, the aim was to examine the effects of diabetes and preventive and intervention chelator therapy with trientine on a preparation that has well-defined NO and EDHF-mediated responses, the rat mesenteric vascular bed. In phenylephrine-preconstricted preparations, maximum vasodilation to acetylcholine was reduced by 35 and 44% after 4 and 8 weeks of streptozotocin-induced diabetes, respectively. Trientine treatment over the first 4 weeks gave 72% protection; intervention therapy over the final 4 weeks prevented deterioration and corrected the initial deficit by 68%. These responses depend on both NO and EDHF. When the latter mechanism was isolated by NO synthase inhibition, diabetic deficits of 53.4 (4 weeks) and 65.4% (8 weeks) were revealed, that were 65% prevented and 50% corrected by trientine treatment. Neither diabetes nor trientine altered vascular smooth muscle responses to the NO donor, sodium nitroprusside (SNP). Thus, the data suggest that metal catalysed ROS production makes a substantial contribution to defects in both the EDHF and NO endothelial mechanisms in diabetes, which has

  2. Aronia melanocarpa juice, a rich source of polyphenols, induces endothelium-dependent relaxations in porcine coronary arteries via the redox-sensitive activation of endothelial nitric oxide synthase.

    PubMed

    Kim, Jong Hun; Auger, Cyril; Kurita, Ikuko; Anselm, Eric; Rivoarilala, Lalainasoa Odile; Lee, Hyong Joo; Lee, Ki Won; Schini-Kerth, Valérie B

    2013-11-30

    This study examined the ability of Aronia melanocarpa (chokeberry) juice, a rich source of polyphenols, to cause NO-mediated endothelium-dependent relaxations of isolated coronary arteries and, if so, to determine the underlying mechanism and the active polyphenols. A. melanocarpa juice caused potent endothelium-dependent relaxations in porcine coronary artery rings. Relaxations to A. melanocarpa juice were minimally affected by inhibition of the formation of vasoactive prostanoids and endothelium-derived hyperpolarizing factor-mediated responses, and markedly reduced by N(ω)-nitro-l-arginine (endothelial NO synthase (eNOS) inhibitor), membrane permeant analogs of superoxide dismutase and catalase, PP2 (Src kinase inhibitor), and wortmannin (PI3-kinase inhibitor). In cultured endothelial cells, A. melanocarpa juice increased the formation of NO as assessed by electron paramagnetic resonance spectroscopy using the spin trap iron(II)diethyldithiocarbamate, and reactive oxygen species using dihydroethidium. These responses were associated with the redox-sensitive phosphorylation of Src, Akt and eNOS. A. melanocarpa juice-derived fractions containing conjugated cyanidins and chlorogenic acids induced the phosphorylation of Akt and eNOS. The present findings indicate that A. melanocarpa juice is a potent stimulator of the endothelial formation of NO in coronary arteries; this effect involves the phosphorylation of eNOS via the redox-sensitive activation of the Src/PI3-kinase/Akt pathway mostly by conjugated cyanidins and chlorogenic acids. Copyright © 2013. Published by Elsevier Inc.

  3. Reduced Endothelium-Dependent Relaxation to Anandamide in Mesenteric Arteries from Young Obese Zucker Rats

    PubMed Central

    Lobato, Nubia S.; Filgueira, Fernando P.; Prakash, Roshini; Giachini, Fernanda R.; Ergul, Adviye; Carvalho, Maria Helena C.; Webb, R. Clinton; Tostes, Rita C.; Fortes, Zuleica B.

    2013-01-01

    Impaired vascular function, manifested by an altered ability of the endothelium to release endothelium-derived relaxing factors and endothelium-derived contracting factors, is consistently reported in obesity. Considering that the endothelium plays a major role in the relaxant response to the cannabinoid agonist anandamide, the present study tested the hypothesis that vascular relaxation to anandamide is decreased in obese rats. Mechanisms contributing to decreased anandamide-induced vasodilation were determined. Resistance mesenteric arteries from young obese Zucker rats (OZRs) and their lean counterparts (LZRs) were used. Vascular reactivity was evaluated in a myograph for isometric tension recording. Protein expression and localization were analyzed by Western blotting and immunofluorescence, respectively. Vasorelaxation to anandamide, acetylcholine, and sodium nitroprusside, as well as to CB1, CB2, and TRPV1 agonists was decreased in endothelium-intact mesenteric arteries from OZRs. Incubation with an AMP-dependent protein kinase (AMPK) activator or a fatty acid amide hydrolase inhibitor restored anandamide-induced vascular relaxation in OZRs. CB1 and CB2 receptors protein expression was decreased in arteries from OZRs. Incubation of mesenteric arteries with anandamide evoked endothelial nitric oxide synthase (eNOS), AMPK and acetyl CoA carboxylase phosphorylation in LZRs, whereas it decreased phosphorylation of these proteins in OZRs. In conclusion, obesity decreases anandamide-induced relaxation in resistance arteries. Decreased cannabinoid receptors expression, increased anandamide degradation, decreased AMPK/eNOS activity as well as impairment of the response mediated by TRPV1 activation seem to contribute to reduce responses to cannabinoid agonists in obesity. PMID:23667622

  4. Pomegranate Extract Enhances Endothelium-Dependent Coronary Relaxation in Isolated Perfused Hearts from Spontaneously Hypertensive Ovariectomized Rats

    PubMed Central

    Delgado, Nathalie T. B.; Rouver, Wender do N.; Freitas-Lima, Leandro C.; de Paula, Tiago D.-C.; Duarte, Andressa; Silva, Josiane F.; Lemos, Virgínia S.; Santos, Alexandre M. C.; Mauad, Helder; Santos, Roger L.; Moysés, Margareth R.

    2017-01-01

    prevented the decreasing in plasmatic nitrite. We observed a reduction in total cholesterol and LDL in the Sham-PHE group. The treatment with PHE enhances the endothelium-dependent coronary relaxation and improves cardiovascular parameters, which suggests a therapeutic role of PHE. PMID:28101057

  5. [Intracellular signal systems in the epithelium- and endothelium-dependent relaxation of smooth muscles].

    PubMed

    Kapilevich, L V; Kovalev, I V; Baskakov, M B; Medvedev, M A

    2001-01-01

    The research of mechanisms of a regulation electrical and contractile of properties of unstriated muscles of an internals remains by an actual problem of modern physiology and medicine. Already now it is possible to state that the efficacy of means of correction of distresses of an internals depends on a degree of a level of scrutiny of these mechanisms. Among physiologically active substances effecting on smooth muscle cells (SM), the special relaxing factor synthesized by endotheliocytes, epithelial cells and SM. Identified by the majority of the explorers as oxide of nitrogen (NO), relaxing factor responds for exhibiting of many myogenic responses of pots and pneumatic routes. The mechanisms of synthesis and implementation of effects of this factor in SM cells up to the extremity are not clarified. The considerable advance in learning mechanisms of operation relaxing factor on SM is connected to discovering of ability of some nitro compounds to replicate NO-dependent relaxing effects in these cells. The main systems of intracellular regulation are involved in mechanisms of implementation endothelial and epithelial local regulatory effects on SM. The majority of the explorers bind an epithelium-dependent release phenomenon SM to an activation of a solvable fraction guanilatcyclase, found in the majority of cells, and effects of cGMP-dependent protein kinases. There are reports on ability of inhibitors NO-sintase to depress a release phenomenon SM of pots and bronchuses, about dependence of a mechanical strain SM of pots and respiratory tract from a contents cGMP in cells. However there are datas giving establishments to guess, that alongside with guanilatciclase in a release phenomenon SM, induced relaxing factors or nitro compounds, the immediate involvement is accepted by cAMP-dependent protein kinases. The most probable point of interaction cAMP and cGMP-dependent processes is phospodiesterase of cyclic nucleotides. It citosolium the enzyme labilized by

  6. Type 1 diabetes and hypercholesterolaemia reveal the contribution of endothelium-derived hyperpolarizing factor to endothelium-dependent relaxation of the rat aorta.

    PubMed

    Malakul, Wachirawadee; Thirawarapan, Suwan; Suvitayavat, Wisuda; Woodman, Owen L

    2008-02-01

    1. The present study evaluated the effect of diabetes, hypercholesterolaemia and their combination on the contribution of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) to relaxation of rat isolated aortic rings and the potential contribution of oxidant stress to the disturbance of endothelial function. 2. Thoracic aortic rings from control, diabetic, hypercholesterolaemic and diabetic plus hypercholesterolaemic rats were suspended in organ baths for tension recording. Generation of superoxide by the aorta was measured using lucigenin-enhanced chemiluminescence. 3. The maximal response to acetylcholine (ACh) was significantly reduced in diabetic or hypercholesterolaemic rats compared with control rats. In rats with diabetes plus hypercholesterolaemia, both the sensitivity and maximal response to ACh was impaired. In control rats, the response to ACh was abolished by the NO synthase inhibitor N(G)-nitro-L-arginine (L-NNA) or inhibition of soluble guanylate cyclase with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). In contrast, in rats with diabetes, hypercholesterolaemia or both, relaxation to ACh was resistant to inhibition by L-NNA or ODQ, but abolished by additional inhibition of K(Ca) channels with charybdotoxin plus apamin. 4. The generation of superoxide was not significantly enhanced in aortic rings from either diabetic or hypercholesterolaemic rats, but was significantly increased in aortic rings from rats with diabetes plus hypercholesterolaemia. 5. These results suggest that when diabetes and hypercholesterolaemia impair endothelium-dependent relaxation, due to a diminished contribution from NO, a compensatory contribution of EDHF to endothelium-dependent relaxation of the aorta is revealed. The attenuation of NO-mediated relaxation, at least in the presence of both diabetes and hypercholesterolaemia, is associated with enhanced superoxide generation.

  7. Vascular Protective Effect of an Ethanol Extract of Camellia japonica Fruit: Endothelium-Dependent Relaxation of Coronary Artery and Reduction of Smooth Muscle Cell Migration.

    PubMed

    Park, Sin-Hee; Shim, Bong-Sup; Yoon, Jun-Seong; Lee, Hyun-Ho; Lee, Hye-Won; Yoo, Seok-Bong; Wi, An-Jin; Park, Whoa-Shig; Kim, Hyun-Jung; Kim, Dong-Wok; Oak, Min-Ho

    2015-01-01

    Camellia japonica is a popular garden plant in Asia and widely used as cosmetic sources and traditional medicine. However, the possibility that C. japonica affects cardiovascular system remains unclear. The aim of the present study was to evaluate vascular effects of an extract of C. japonica. Vascular reactivity was assessed in organ baths using porcine coronary arteries and inhibition of proliferation and migration were assessed using human vascular smooth muscle cells (VSMCs). All four different parts, leaf, stem, flower, and fruits, caused concentration-dependent relaxations and C. japonica fruit (CJF) extract showed the strongest vasorelaxation and its effect was endothelium dependent. Relaxations to CJF were markedly reduced by inhibitor of endothelial nitric oxide synthase (eNOS) and inhibitor of PI3-kinase, but not affected by inhibitor of cyclooxygenase and endothelium-derived hyperpolarizing factor-mediated response. CJF induced activated a time- and concentration-dependent phosphorylation of eNOS in endothelial cells. Altogether, these studies have demonstrated that CJF is a potent endothelium-dependent vasodilator and this effect was involved in, at least in part, PI3K-eNOS-NO pathway. Moreover, CJF attenuated TNF-α induced proliferation and PDGF-BB induced migration of VSMCs. The present findings indicate that CJF could be a valuable candidate of herbal medicine for cardiovascular diseases associated with endothelial dysfunction and atherosclerosis.

  8. Long-lasting endothelium-dependent relaxation of isolated arteries caused by an extract from the bark of Combretum leprosum

    PubMed Central

    Alves, Francisco das Chagas; Cavalcanti, Paulo Marques da Silva; Passaglia, Rita de Cassia Aleixo Tostes; Ballejo, Gustavo

    2015-01-01

    Objective To describe and to characterize the relaxing effect of an extract of the bark of Combretum leprosum on isolated arterial rings from different animals. Methods Rings (3 to 4mm) from rabbit, rat, or porcine arteries rings were suspended in an organ bath (Krebs, 37°C, 95%O2/5%CO2) to record isometric contractions. After the stabilization period (2 to 3 hours) contractions were induced by the addition of phenylephrine (0.1 to 0.3µM) or U46619 (10 to 100nM), and Combretum leprosum extract was added on the plateau of the contractions. Experiments were performed to determine the potency, duration, reversibility, and to get insights on the potential mechanism involved in extract-induced relaxations. Results In all rings tested, Combretumleprosum extract (1.5μg/mL) was able to cause relaxations, which were strictly endothelium-dependent. In rabbit or rat thoracic aorta rings, the relaxations were reversed by vitamin B12a or L-NG-nitroarginine. In porcine right coronary arteries and rabbit abdominal aorta, extract caused both L-NG-nitroarginine-sensitive and L-NG-nitroarginine-resistant relaxations. In rabbit thoracic aorta, the extract was relatively potent (EC50=0.20µg/mL) and caused relaxations; intriguingly the endothelium continued to produce relaxing factors for a long period after removing the extract. The magnitude of extract-induced relaxations was significantly reduced in the absence of extracellular Ca2+; in addition, the TRPs channels blocker ruthenium red (10µM) was able to revert extract-induced relaxations. Phytochemical analyses indicated that the extract was rich in polyphenol-like reacting substances. Conclusions Combretum leprosum extract contains bioactive compounds capable of promoting Ca2+-dependent stimulation of endothelial cells which results in a prolonged production of relaxing factors. PMID:26466063

  9. The DPP-4 inhibitor linagliptin and the GLP-1 receptor agonist exendin-4 improve endothelium-dependent relaxation of rat mesenteric arteries in the presence of high glucose.

    PubMed

    Salheen, S M; Panchapakesan, U; Pollock, C A; Woodman, O L

    2015-04-01

    The aim of the study was to investigate the effects of the DPP-4 inhibitors and GLP-1R agonist, exendin-4 on the mechanism(s) of endothelium-dependent relaxation in rat mesenteric arteries exposed to high glucose concentration (40 mM). Organ bath techniques were employed to investigate vascular endothelial function in rat mesenteric arteries in the presence of normal (11 mM) or high (40 mM) glucose concentrations. Pharmacological tools (1μM TRAM-34, 1μM apamin, 100 nM Ibtx, 100 μM l-NNA, 10 μM ODQ) were used to distinguish between NO and EDHF-mediated relaxation. Superoxide anion levels were assessed by L-012 and lucigenin enhanced-chemiluminescence techniques. Incubation of mesenteric rings with high glucose for 2 h caused a significant increase in superoxide anion generation and a significant impairment of endothelium-dependent relaxation. Exendin-4 and DPP-4 inhibitor linagliptin, but not sitagliptin or vildagliptin, significantly reduced vascular superoxide and improved endothelium-dependent relaxation in the presence of high glucose. The beneficial actions of exendin-4, but not linagliptin, were attenuated by the GLP-1R antagonist exendin fragment (9-39). Further experiments demonstrated that the presence of high glucose impaired the contribution of both nitric oxide and endothelium-dependent hyperpolarisation to relaxation and that linagliptin improved both mechanisms involved in endothelium-dependent relaxation. These findings demonstrate that high glucose impaired endothelium-dependent relaxation can be improved by exendin-4 and linagliptin, likely due to their antioxidant activity and independently of any glucose lowering effect.

  10. Role of gender and estrogen receptors in the rat aorta endothelium-dependent relaxation to red wine polyphenols.

    PubMed

    Kane, Modou Oumy; Anselm, Eric; Rattmann, Yanna Dantas; Auger, Cyril; Schini-Kerth, Valérie B

    2009-01-01

    Regular intake of moderate amounts of beverages rich in polyphenols such as red wine is associated with a protective effect on the vascular system, in part, by increasing the endothelial formation of nitric oxide (NO), a major vasoprotective factor. Since estrogens are potent inducers of NO formation and polyphenols have been shown to have phytoestrogen properties, we determined whether estrogen receptors mediate the stimulatory effect of red wine polyphenols (RWPs) on the endothelial formation of NO using isolated rat aortic rings and cultured endothelial cells. RWPs caused endothelium-dependent relaxations, which were more pronounced in the aorta of female than male rats. Increased relaxations were also observed to acetylcholine but not to sodium nitroprusside. Relaxations to RWPs were abolished by nitro l-arginine and MnTMPyP, markedly reduced by polyethyleneglycol-catalase and wortmannin, and not affected by the estrogen antagonist ICI 182,780 in aortic rings from males and females. eNOS expression was higher in aortic sections of female than male rats. RWPs caused the phosphorylation of Akt and eNOS in endothelial cells, which was unaffected by ICI 182,780. Thus, RWPs cause redox-sensitive PI3-kinase/Akt-dependent NO-mediated relaxations, which are more pronounced in the aorta of female than male rats; an effect most likely due to the increased expression level of eNOS rather than activation of estrogen receptors.

  11. Chronic treatment with taurine ameliorates diabetes-induced dysfunction of nitric oxide-mediated neurogenic and endothelium-dependent corpus cavernosum relaxation in rats.

    PubMed

    Dalaklioglu, Selvinaz; Kuscu, Nilay; Celik-Ozenci, Ciler; Bayram, Zeliha; Nacitarhan, Cahit; Ozdem, Sadi Satilmis

    2014-08-01

    This study was aimed to examine the effect of chronic taurine treatment on corpus cavernosum dysfunction in diabetic rats and to investigate possible underlying mechanisms. Thirty male rats were randomized to three groups of 10 each, including control, diabetic, and taurine-treated diabetic. Diabetes was induced in rats by streptozotocin (STZ, single intraperitoneal dose of 50 mg/kg body weight). Taurine was administered orally for 12 weeks (1% w/v in drinking water) from the day on which STZ was injected. At the end of the 12th week, strips of corpus cavernosum were suspended in an organ bath system for functional studies. Nitric oxide (NO)-mediated endothelium-dependent and neurogenic corpus cavernosum relaxation were evaluated by acetylcholine (ACh, 0.1-100 μm) and electrical field stimulation (EFS, 30 V, 5 ms, 2-32 Hz), respectively. The expressions of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (Ser-1177), neuronal nitric oxide synthase (nNOS), NADPH oxidase subunit gp91(phox) , Rho A, and Rho kinase in corpus cavernosum were semi-quantitatively assessed by immunohistochemistry. Induction of diabetes resulted in significant inhibition of NO-mediated endothelium-dependent and neurogenic corpus cavernosum relaxation. Furthermore, eNOS, p-eNOS, and nNOS expressions decreased significantly in diabetic rats compared to controls, while gp91(phox) , RhoA and Rho kinase expressions increased significantly. The diminished relaxation response to ACh and EFS as well as diabetes-related changes in expressions of these proteins in corpus cavernosum of diabetic rats was significantly improved by taurine. Taurine treatment improves NO-mediated relaxations of corpus cavernosum in diabetic rats probably by inhibiting NADPH oxidase/Rho kinase pathways.

  12. Endothelium-dependent relaxation evoked by ATP and UTP in the aorta of P2Y2-deficient mice.

    PubMed

    Guns, Pieter-Jan D F; Van Assche, Tim; Fransen, Paul; Robaye, Bernard; Boeynaems, Jean-Marie; Bult, Hidde

    2006-03-01

    Based on pharmacological criteria, we previously suggested that in the mouse aorta, endothelium-dependent relaxation by nucleotides is mediated by P2Y1 (adenosine diphosphate (ADP)), P2Y2 (adenosine triphosphate (ATP)) and P2Y6 (uridine diphosphate (UDP)) receptors. For UTP, it was unclear whether P2Y2, P2Y6 or yet another subtype was involved. Therefore, in view of the lack of selective purinergic agonists and antagonists, we used P2Y2-deficient mice to clarify the action of UTP. Thoracic aorta segments (width 2 mm) of P2Y2-deficient and wild-type (WT) mice were mounted in organ baths to measure isometric force development and intracellular calcium signalling. Relaxations evoked by ADP, UDP and acetylcholine were identical in knockout and WT mice, indicating that the receptors for these agonists function normally. P2Y2-deficient mice showed impaired ATP- and adenosine 5'[gamma-thio] triphosphate (ATPgammaS)-evoked relaxation, suggesting that in WT mice, ATP and ATPgammaS activate predominantly the P2Y2 subtype. The ATP/ATPgammaS-evoked relaxation and calcium signals in the knockout mice were partially rescued by P2Y1, as they were sensitive to 2'-deoxy-N6-methyladenosine 3',5'-bisphosphate (MRS2179), a P2Y1-selective antagonist. In contrast to ATP, the UTP-evoked relaxation was not different between knockout and WT mice. Moreover, the action of UTP was not sensitive to MRS2179. Therefore, the action of UTP is probably mediated mainly by a P2Y6(like) receptor subtype. In conclusion, we demonstrated that ATP-evoked relaxation of the murine aorta is mainly mediated by P2Y2. But this P2Y2 receptor has apparently no major role in UTP-evoked relaxation. The vasodilator effect of UTP is probably mediated mainly by a P2Y6(like) receptor.

  13. [Endothelium-dependent relaxation of Wistar rat aorta in late pregnancy].

    PubMed

    Dieye, A M; Faye, B; Gairard, A

    2001-01-01

    Some authors usually described an enhanced vascular reactivity to vasodilatoragents during pregancy. We would like toverifythis hypothesis with acetylcholin which is the vasodilator agent habitually used in animal experimentation. Young adult Wistar rats, pregnant and nonpregnant, were used. Rats received either a control diet, or this control diet supplemented with nitroargininin (0.063 % i.e. 30 mg/kg for7 days [treated group], from day 13th to day 20th for pregnants. Relaxation of rings thoracic aorta, with or without endothelium, in the presence of acetylcholin in cumulative was studied after contraction induced by depolarisation with KCl or after noradrenalin addition. The results show that relaxation in the presence of acetylcholin needs functional endothelial cells and that the nitric oxide plays a key role in this relaxation. So, there is no difference in vascular reactivity in late pregnant rats compared to nonpregnant rats. In addition, chronic inhibition of nitric oxide synthesis in pregnant rats do not modify pregnancy reactivity to nitric oxide because relaxation to S-nitroso-N acetyl penicillamin, which is a nitric oxide donor, is not different in control pregnant rats compared to treated pregnant rats. A judicious observation of work conditions with a particular attention with calcium concentration in organ bath solutions would certainly explain contradictory results obtained by different authors on vascular reactivity in vitro during gestation.

  14. Paullinia pinnata extracts rich in polyphenols promote vascular relaxation via endothelium-dependent mechanisms.

    PubMed

    Zamble, Alexis; Carpentier, Marie; Kandoussi, Abdelmejid; Sahpaz, Sevser; Petrault, Olivier; Ouk, Tawarak; Hennuyer, Nathalie; Fruchart, Jean-Charles; Staels, Bart; Bordet, Régis; Duriez, Patrick; Bailleul, François; Martin-Nizard, Françoise

    2006-04-01

    Paullinia pinnata L. (Sapindaceae) is an African tropical plant whose roots and leaves are used in traditional medicine for many purposes, especially for erectile dysfunction, but its action mechanism is unknown. P. pinnata root and leaf methanolic extracts are rich in phenolic compounds. This study shows that both extracts are highly antioxidative and induce a slight transcriptional activity of peroxisome proliferator activated receptor-alpha. They also increased and decreased endothelial nitric oxide synthase and endothelin-1 mRNA levels in bovine aortic endothelial cells, respectively. In this study P. pinnata methanolic extracts in cumulative doses elicited in a dose-dependent manner the relaxation of phenylephrine precontracted isolated rat aortic rings. N-nitro-L-arginine methyl ester significantly attenuated the capacity of both extracts to induce arterial relaxation, indicating that this arterial relaxation was mediated by endothelial nitric oxide release. It could be suggested that the arterial relaxation induced by both extracts could be mainly linked to their capacities to inhibit nitric oxide oxidation through their antioxidant properties.

  15. Heme oxygenase 2: endothelial and neuronal localization and role in endothelium-dependent relaxation.

    PubMed Central

    Zakhary, R; Gaine, S P; Dinerman, J L; Ruat, M; Flavahan, N A; Snyder, S H

    1996-01-01

    Heme oxygenase 2 (HO-2), which synthesizes carbon monoxide (CO), has been localized by immunohistochemistry to endothelial cells and adventitial nerves of blood vessels. HO-2 is also localized to neurons in autonomic ganglia, including the petrosal, superior cervical, and nodose ganglia, as well as ganglia in the myenteric plexus of the intestine. Enzyme studies demonstrated that tin protoporphyrin-9 is a selective inhibitor of HO with approximately 10-fold selectivity for HO over endothelial nitric oxide synthase (NOS) and soluble guanylyl cyclase. Inhibition of HO activity by tin protoporphyrin 9 reverses the component of endothelial-derived relaxation of porcine distal pulmonary arteries not reversed by an inhibitor of NOS. Thus, CO, like NO, may have endothelial-derived relaxing activity. The similarity of NOS and HO-2 localizations and functions in blood vessels and the autonomic nervous system implies complementary and possibly coordinated physiologic roles for these two mediators. Images Fig. 1 Fig. 2 Fig. 3 PMID:8570637

  16. 5-Methyltetrahydrofolate and tetrahydrobiopterin can modulate electrotonically mediated endothelium-dependent vascular relaxation.

    PubMed

    Griffith, Tudor M; Chaytor, Andrew T; Bakker, Linda M; Edwards, David H

    2005-05-10

    We have investigated the ability of 5-methyltetrahydrofolate (5-MTHF) and tetrahydrobiopterin (BH(4)) to modulate nitric oxide (NO)-independent vascular relaxations that are mediated by the sequential spread of endothelial hyperpolarization through the wall of the rabbit iliac artery by means of myoendothelial and homocellular smooth muscle gap junctions. Relaxations and subintimal smooth muscle hyperpolarizations evoked by cyclopiazonic acid were depressed by the gap junction inhibitor 2-aminoethoxydiphenyl borate, whose effects were prevented by 5-MTHF and BH(4), but not by their oxidized forms folic acid and 7,8-dihydrobiopterin. Analogously, 5-MTHF and BH(4), but not folic acid or 7,8-dihydrobiopterin, attenuated the depression of subintimal hyperpolarization by a connexin-mimetic peptide targeted against Cx37 and Cx40 ((37,40)Gap 26) and the depression of subadventitial hyperpolarization by a peptide targeted against Cx43 ((43)Gap 26), thus reflecting the known differential expression of Cx37 and Cx40 in the endothelium and Cx43 in the media of the rabbit iliac artery. The inhibitory effects of 2-aminoethoxydiphenyl borate and (37,40)Gap 26 against subintimal hyperpolarization were prevented by catalase, which destroys H(2)O(2). 5-MTHF and BH(4) thus appear capable of modulating electrotonic signaling by means of myoendothelial and smooth muscle gap junctions by reducing oxidant stress, potentially conferring an ability to reverse the endothelial dysfunction found in disease states through mechanisms that are independent of NO.

  17. Involvement of histamine in endothelium-dependent relaxation of mesenteric lymphatic vessels.

    PubMed

    Nizamutdinova, Irina Tsoy; Maejima, Daisuke; Nagai, Takashi; Bridenbaugh, Eric; Thangaswamy, Sangeetha; Chatterjee, Victor; Meininger, Cynthia J; Gashev, Anatoliy A

    2014-10-01

    The knowledge of the basic principles of lymphatic function, still remains, to a large degree, rudimentary and will require significant research efforts. Recent studies of the physiology of the MLVs suggested the presence of an EDRF other than NO. In this study, we tested the hypothesis that lymphatic endothelium-derived histamine relaxes MLVs. We measured and analyzed parameters of lymphatic contractility in isolated and pressurized rat MLVs under control conditions and after pharmacological blockade of NO by L-NAME (100 μM) or/and histamine production by α-MHD (10 μM). Effectiveness of α-MHD was confirmed immunohistochemically. We also used immunohistochemical labeling and Western blot analysis of the histamine-producing enzyme, HDC. In addition, we blocked HDC protein expression in MLVs by transient transfection with vivo-morpholino oligos. We found that only combined pharmacological blockade of NO and histamine production completely eliminates flow-dependent relaxation of lymphatic vessels, thus confirming a role for histamine as an EDRF in MLVs. We also confirmed the presence of HDC and histamine inside lymphatic endothelial cells. This study supports a role for histamine as an EDRF in MLVs. © 2014 John Wiley & Sons Ltd.

  18. Endothelium-dependent relaxation evoked by ATP and UTP in the aorta of P2Y2-deficient mice

    PubMed Central

    Guns, Pieter-Jan D F; Van Assche, Tim; Fransen, Paul; Robaye, Bernard; Boeynaems, Jean-Marie; Bult, Hidde

    2006-01-01

    Based on pharmacological criteria, we previously suggested that in the mouse aorta, endothelium-dependent relaxation by nucleotides is mediated by P2Y1 (adenosine diphosphate (ADP)), P2Y2 (adenosine triphosphate (ATP)) and P2Y6 (uridine diphosphate (UDP)) receptors. For UTP, it was unclear whether P2Y2, P2Y6 or yet another subtype was involved. Therefore, in view of the lack of selective purinergic agonists and antagonists, we used P2Y2-deficient mice to clarify the action of UTP. Thoracic aorta segments (width 2 mm) of P2Y2-deficient and wild-type (WT) mice were mounted in organ baths to measure isometric force development and intracellular calcium signalling. Relaxations evoked by ADP, UDP and acetylcholine were identical in knockout and WT mice, indicating that the receptors for these agonists function normally. P2Y2-deficient mice showed impaired ATP- and adenosine 5′[γ-thio] triphosphate (ATPγS)-evoked relaxation, suggesting that in WT mice, ATP and ATPγS activate predominantly the P2Y2 subtype. The ATP/ATPγS-evoked relaxation and calcium signals in the knockout mice were partially rescued by P2Y1, as they were sensitive to 2′-deoxy-N6-methyladenosine 3′,5′-bisphosphate (MRS2179), a P2Y1-selective antagonist. In contrast to ATP, the UTP-evoked relaxation was not different between knockout and WT mice. Moreover, the action of UTP was not sensitive to MRS2179. Therefore, the action of UTP is probably mediated mainly by a P2Y6(like) receptor subtype. In conclusion, we demonstrated that ATP-evoked relaxation of the murine aorta is mainly mediated by P2Y2. But this P2Y2 receptor has apparently no major role in UTP-evoked relaxation. The vasodilator effect of UTP is probably mediated mainly by a P2Y6(like) receptor. PMID:16415908

  19. Chronic administration of nicotine-free cigarette smoke extract impaired endothelium-dependent vascular relaxation in rats via increased vascular oxidative stress.

    PubMed

    Shimosato, Takashi; Geddawy, Ayman; Tawa, Masashi; Imamura, Takeshi; Okamura, Tomio

    2012-01-01

    Cigarette smoking has been implicated in the initiation and progression of cardiovascular disorders and atherosclerosis. Here, we examined the effects of nicotine-free cigarette smoke extract (CSE) on the regulation of cardiovascular function. Rats were subcutaneously administered PBS or nicotine-free CSE at 0.05 to 1.5 mL/day per rat for 4 weeks. Blood pressure, cardiac function, and vascular responsiveness were measured at 4 weeks after administration. Furthermore, acute effects of nicotine-free CSE were also studied in the aorta isolated from normal rats. Blood pressure and left ventricular systolic pressure (LVSP) were significantly increased in the nicotine-free CSE-administered rats, but heart rate, dP/dt(max), and dP/dt(min) were not affected. Endothelium-dependent relaxation by acetylcholine (ACh) in the nicotine-free CSE-treated rats was significantly attenuated compared to PBS-treated rats, but endothelium-independent relaxation by sodium nitroprusside (SNP) did not differ. Pretreatment with superoxide dismutase restored the attenuated ACh-induced relaxation. Contractions by phenylephrine, angiotensin II, and KCl did not differ between two groups. In vitro acute nicotine-free CSE treatment did not alter the response to ACh or SNP. These results suggest that chronic nicotine-free CSE administration impairs endothelial function by increased production of superoxide derived from the vascular wall components other than smooth muscles and induces slight hypertension accompanied with LVSP elevation.

  20. Endothelium-dependent relaxation to acetylcholine in bovine oviductal arteries: mediation by nitric oxide and changes in apamin-sensitive K+ conductance.

    PubMed Central

    García-Pascual, A.; Labadía, A.; Jimenez, E.; Costa, G.

    1995-01-01

    1. Mechanisms underlying the relaxant response to acetylcholine (ACh) were examined in bovine oviductal arteries (o.d. 300-500 microns and i.d. 150-300 microns) in vitro. Vascular rings were treated with indomethacin (10 microM) to prevent the effects of prostaglandins. 2. ACh elicited a concentration-related relaxation in ring segments precontracted with noradrenaline (NA), which was abolished by endothelium denudation. 3. The ACh-induced relaxation was attenuated but not abolished by NG-nitro-L-arginine (L-NOARG, 1 microM-1 mM), an inhibitor of nitric oxide (NO) formation. The inhibition caused by L-NOARG (10 microM) was reversed by addition of excess of L-arginine but not D-arginine (1 mM). 4. In high K+ (40-60 mM)-contracted rings, ACh was a much less effective vasodilator and its relaxant response was completely abolished by L-NOARG (100 microM). 5. In NA (10 microM)-contracted rings, ACh induced sustained and concentration-dependent increases in cyclic GMP, which were reduced below basal values by L-NOARG (100 microM), while potent relaxation persisted. Similar increases in cyclic GMP were evoked by ACh in high K+ (50 mM)-treated arteries and under these conditions, both cyclic GMP accumulation and relaxation were L-NOARG-sensitive. 6. S-nitroso-L-cysteine (NC), a proposed endogenous precursor of endothelial NO, also induced cyclic GMP accumulation in NA-contracted oviductal arteries. 7. Methylene blue (MB, 10 microM), a proposed inhibitor of soluble guanylate cyclase, inhibited both endothelium-dependent relaxation to ACh and endothelium-independent response to exogenous NO, whereas relaxation to NC remained unaffected. 8. The L-NOARG-resistant response to ACh was not affected by either ouabain (0.5 mM), glibenclamide (3 microM), tetraethylammonium (TEA, 1 mM) or charybdotoxin (50 nM), but was selectively blocked by apamin (0.1-1 microM). However, apamin did not inhibit either relaxation to ACh in high K(+)-contracted rings or endothelium

  1. Brazilin isolated from the heartwood of Caesalpinia sappan L induces endothelium-dependent and -independent relaxation of rat aortic rings

    PubMed Central

    Yan, Yu; Chen, Yu-cai; Lin, Yi-huang; Guo, Jing; Niu, Zi-ran; Li, Li; Wang, Shou-bao; Fang, Lian-hua; Du, Guan-hua

    2015-01-01

    Aim: Brazilin is one of the major constituents of Caesalpinia sappan L with various biological activities. This study sought to investigate the vasorelaxant effect of brazilin on isolated rat thoracic aorta and explore the underlying mechanisms. Methods: Endothelium-intact and -denuded aortic rings were prepared from rats. The tension of the preparations was recorded isometrically with a force displacement transducer connected to a polygraph. The phosphorylation levels of ERK1/2 and myosin light chain (MLC) were analyzed using Western blotting assay. Results: Application of brazilin (10–100 μmol/L) dose-dependently relaxed the NE- or high K+-induced sustained contraction of endothelium-intact aortic rings (the EC50 was 83.51±5.6 and 79.79±4.57 μmol/L, respectively). The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin. In addition, pre-incubation with brazilin dose-dependently attenuated the vasoconstriction induced by KCl, NE or Ang II. Pre-incubation with brazilin also markedly suppressed the high K+-induced extracellular Ca2+ influx and NE-induced intracellular Ca2+ release in endothelium-denuded aortic rings. Pre-incubation with brazilin dose-dependently inhibited the NE-stimulated phosphorylation of ERK1/2 and MLC in both endothelium-intact and -denuded aortic rings. Conclusion: Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC. Brazilin also attenuates vasoconstriction via blocking voltage- and receptor-operated Ca2+ channels. PMID:26564314

  2. Endothelium-dependent relaxation and hyperpolarization of canine coronary artery smooth muscles in relation to the electrogenic Na-K pump.

    PubMed Central

    Chen, G.; Hashitani, H.; Suzuki, H.

    1989-01-01

    1 In the smooth muscle cells of canine coronary artery, acetylcholine (ACh) produced a transient, endothelium-dependent hyperpolarization of the membrane. A similar hyperpolarization was also elicited by exposure to Krebs solution after incubation of the artery in K-free solution for 30 min. 2 A hyperpolarization of reproducible amplitude was generated when ACh was applied at intervals greater than 30 min. Repetitive application of ACh at 15 min intervals caused a successive reduction in the amplitude of hyperpolarization. 3 The reduction in the amplitude of relaxation during five successive applications of ACh at 15 min intervals was less than 10% of the first relaxation. 4 The ACh-induced hyperpolarization was blocked by atropine but not by ouabain, whereas the K-free induced hyperpolarization was blocked by ouabain. In low Na (Li-substituted) solution, ACh still induced a hyperpolarization but the K-free induced hyperpolarization was absent. 5 In coronary artery precontracted by high-K solution, ACh produced an endothelium-dependent relaxation, without membrane hyperpolarization. The associated relaxation was resistant to ouabain but sensitive to atropine. 6 It is concluded that in the canine coronary artery, the electrogenic Na-K pump does not contribute to the endothelium-dependent hyperpolarization or relaxation. The results are consistent with the release of two different inhibitory factors from the vascular endothelium. PMID:2590775

  3. Endothelium-dependent relaxation and hyperpolarization evoked by bradykinin in canine coronary arteries: enhancement by exercise-training.

    PubMed Central

    Mombouli, J. V.; Nakashima, M.; Hamra, M.; Vanhoutte, P. M.

    1996-01-01

    bradykinin were also shifted to the left by perindoprilat. The shift induced by the ACE-inhibitor in either type of preparation was not significantly different. 8. These findings demonstrate that exercise-training augments the sensitivity of the coronary artery of the dog to the endothelium-dependent effects of bradykinin. This sensitization to bradykinin may reflect an increased role of both NO and EDHF, and is not the consequence of differences in ACE activity in the receptor compartment. PMID:8821528

  4. Angiotensin-(1-7) Selectively Induces Relaxation and Modulates Endothelium-Dependent Dilation in Mesenteric Arteries of Salt-Fed Rats.

    PubMed

    Raffai, Gábor; Lombard, Julian H

    2016-01-01

    This study investigated the acute effects of angiotensin-(1-7) and AVE0991 on active tone and vasodilator responses to bradykinin and acetylcholine in isolated mesenteric arteries from Sprague-Dawley rats fed a high-salt (HS; 4% NaCl) versus a normal salt (NS; 0.4% NaCl) diet. Angiotensin-(1-7) and AVE0991 elicited relaxation, and angiotensin-(1-7) unmasked vasodilator responses to bradykinin in arteries from HS-fed rats. These effects of angiotensin-(1-7) and AVE0991 were inhibited by endothelium removal, A779, PD123319, HOE140 and L-NAME. Angiotensin-(1-7) also restored the acetylcholine-induced relaxation that was suppressed by the HS diet. Vasodilator responses to bradykinin and acetylcholine in the presence of angiotensin-(1-7) were mimicked by captopril and the AT2 receptor agonist CGP42112 in arteries from HS-fed rats. Thus, in contrast to salt-induced impairment of vascular relaxation in response to vasodilator stimuli, angiotensin-(1-7) induces endothelium-dependent and NO-mediated relaxation, unmasks bradykinin responses via activation of mas and AT2 receptors, and restores acetylcholine-induced vasodilation in HS-fed rats. AT2 receptor activation and angiotensin-converting enzyme (ACE) inhibition shared the ability of angiotensin-(1-7) to enhance bradykinin and acetylcholine responses in HS-fed rats. These findings suggest a therapeutic potential for mas and/or AT2 receptor activation and ACE inhibition in restoring endothelial function impaired by elevated dietary salt intake or other pathological conditions. © 2016 S. Karger AG, Basel.

  5. Great heterogeneity of commercial fruit juices to induce endothelium-dependent relaxations in isolated porcine coronary arteries: role of the phenolic content and composition.

    PubMed

    Auger, Cyril; Pollet, Brigitte; Arnold, Cécile; Marx, Céline; Schini-Kerth, Valérie B

    2015-01-01

    Since polyphenol-rich products such as red wine, grape juice, and grape extracts have been shown to induce potent endothelium-dependent relaxations, we have evaluated whether commercial fruit juices such as those from berries are also able to induce endothelium-dependent relaxations of isolated coronary arteries and, if so, to determine whether this effect is related to their phenolic content. Among the 51 fruit juices tested, 2/12 grape juices, 3/7 blackcurrant juices, 4/5 cranberry juices, 1/6 apple juices, 0/5 orange juices, 2/6 red fruit and berry juices, 3/6 blends of red fruit juices, and 0/4 non-red fruit juices were able to induce relaxations achieving more than 50% at a volume of 1%. The active fruit juices had phenolic contents ranging from 0.31 to 1.86 g GAE/L, which were similar to those of most of the less active juices with the exception of one active grape juice (2.14 g GAE/L) and one active blend of red fruit juices (3.48 g GAE/L). Altogether, these findings indicate that very few commercial fruit juices have the ability to induce potent endothelium-dependent relaxations, and that this effect is not related to their quantitative phenolic content, but rather to their qualitative phenolic composition.

  6. Black cohosh (Cimicifuga racemosa) relaxes the isolated rat thoracic aorta through endothelium-dependent and -independent mechanisms.

    PubMed

    Kim, Eun-Young; Lee, Young Joo; Rhyu, Mee-Ra

    2011-11-18

    The rhizome of the Cimicifuga racemosa (commonly known as black cohosh) has been used in treatment of climacteric complaints for decades in North America and Europe. A number of studies investigated the estrogenic potential of black cohosh, but its effectiveness is still controversial. Recently, it was reported that the extract of black cohosh acted as an agonist at the serotonin (5-HT) receptor and 5-HT derivative was isolated out of the black cohosh extract. Because it is well known that the 5-HT elicited the various cardiovascular effects including vasorelaxation, we investigated the vasorelaxant effects of the extract of black cohosh and its possible mechanisms of action. The extract of black cohosh (BcEx) was examined for its vasorelaxant effects in isolated rat aorta. The aortic rings were equilibrated under resting tension and induced reproducible contraction in organ bath. The control contraction was produced by 300 nM NE, and then BcEx were added. In experiments where specific inhibitors were used, they were added 20 min before NE contraction. BcEx elicited two phases of relaxation in rat aorta pre-contracted with norepinephrine. The first, a rapid relaxation, which occurred within seconds of BcEx administration, was eliminated by pretreatment with N(G)-nitro-l-arginine (l-NNA) or methylene blue. The endogenous NO synthase substrate l-Arg markedly reversed the action of l-NNA, indicating that BcEx elicited the vasorelaxant effect via the NO/cGMP pathway. The second, slowly developing relaxation was not affected by the endothelium denudation. BcEx-induced endothelium-independent vasorelaxation appears to involve the inhibition of calcium influx mediated by the opening of inward rectifier potassium channels. BcEx elicits the vasorelaxant effect via endothelium-dependent and -independent mechanisms and may contribute to a better understanding of a potential link between the use of black cohosh and its beneficial effects on vascular health. Copyright © 2011

  7. Resveratrol Ameliorates Clonidine-Induced Endothelium-Dependent Relaxation Involving Akt and Endothelial Nitric Oxide Synthase Regulation in Type 2 Diabetic Mice.

    PubMed

    Taguchi, Kumiko; Hida, Mari; Matsumoto, Takayuki; Kobayashi, Tsuneo

    2015-01-01

    Diabetic vascular complication is one of the manifestations of endothelial dysfunction. Resveratrol (RV) is considered to be beneficial in protecting endothelial function. However, the exact protective effect and mechanisms involved have not been fully clarified. In this study, we investigated the relationship between Akt/endothelial nitric oxide synthase (eNOS) activation and RV in diabetes-induced endothelial dysfunction. Aortas were dissected and placed in organ chambers, and nitric oxide (NO) production in response to acetylcholine (ACh) and RV was measured. ACh-induced endothelium-dependent relaxation was markedly increased in controls by RV pretreatment. Furthermore, RV caused NO-dependent relaxation via the Akt signaling pathway, which was weaker in the aortas of diabetic mice than age-matched controls. To further examine the underlying mechanisms, we measured the phosphorylation of Akt and eNOS by Western blotting. RV caused the phosphorylation of Akt and eNOS in aortas, which was decreased in diabetic mice. However, RV augmented the impaired clonidine-induced relaxation in diabetic mice. Interestingly, the phosphorylation of Akt and eNOS was increased under stimulation with RV and clonidine only in diabetic mice. Thus, either RV or clonidine causes Akt-dependent NO-mediated relaxation, which is weaker in diabetic mice than controls. However, additional exposure to RV and clonidine has an augmenting effect on the Akt/eNOS signaling pathway under diabetic conditions. RV-induced Akt/eNOS activity may be a common link involved in the clonidine-induced Akt/eNOS activity, so RV and clonidine may have a synergistic effect.

  8. Tocotrienol-Rich Tocomin Attenuates Oxidative Stress and Improves Endothelium-Dependent Relaxation in Aortae from Rats Fed a High-Fat Western Diet

    PubMed Central

    Ali, Saher F.; Nguyen, Jason C. D.; Jenkins, Trisha A.; Woodman, Owen L.

    2016-01-01

    We have previously reported that tocomin, a mixture high in tocotrienol content and also containing tocopherol, acutely preserves endothelial function in the presence of oxidative stress. In this study, we investigated whether tocomin treatment would preserve endothelial function in aortae isolated from rats fed a high-fat diet known to cause oxidative stress. Wistar hooded rats were fed a western diet (WD, 21% fat) or control rat chow (standard diet, 6% fat) for 12 weeks. Tocomin (40 mg/kg/day sc) or its vehicle (peanut oil) was administered for the last 4 weeks of the feeding regime. Aortae from WD rats showed an impairment of endothelium-dependent relaxation that was associated with an increased expression of the NADPH oxidase Nox2 subunit and an increase in the vascular generation of superoxide measured using L-012 chemiluminescence. The increase in vascular oxidative stress was accompanied by a decrease in basal NO release and impairment of the contribution of NO to ACh-induced relaxation. The impaired relaxation is likely contributed to by a decreased expression of eNOS, calmodulin, and phosphorylated Akt and an increase in caveolin. Tocotrienol rich tocomin, which prevented the diet-induced changes in vascular function, reduced vascular superoxide production and abolished the diet-induced changes in eNOS and other protein expression. Using selective inhibitors of nitric oxide synthase (NOS), soluble guanylate cyclase (sGC) and calcium-activated potassium (KCa) channels we demonstrated that tocomin increased NO-mediated relaxation, without affecting the contribution of endothelium-dependent hyperpolarization type relaxation to the endothelium-dependent relaxation. The beneficial actions of tocomin in this diet-induced model of obesity suggest that it may have potential to be used as a therapeutic agent to prevent vascular disease in obesity. PMID:27800483

  9. Endomorphins restored the endothelium-dependent relaxation of the rabbit aorta rings exposed to high D-glucose condition via NO-cGMP pathway.

    PubMed

    Liu, Jing; Wu, Wei-Min; Che, Juan-Juan; Zhang, Jun; Wang, Rui

    2006-01-01

    Rings of rabbit aorta that were both incubated in a high concentration of D-glucose and contracted submaximally by phenylephrine showed significantly decreased endothelium-dependent relaxations induced by acetylcholine. The cGMP production of aorta rings was also reduced. Treatment with endomorphins (1-1000 nmol/L) restored acetylcholine-induced relaxations of aorta rings incubated in high glucose concentrations and increased the cGMP synthesis. Moreover, this effect of endomorphins on endothelium was antagonized by naloxone, and the increase in the production of cGMP was also blocked.

  10. Preservation of endothelium-dependent relaxation in cholesterol-fed and streptozotocin-induced diabetic mice by the chronic administration of cholestyramine.

    PubMed Central

    Kamata, K.; Sugiura, M.; Kojima, S.; Kasuya, Y.

    1996-01-01

    1. Experiments were designed to investigate the effects of the low density lipoprotein (LDL)-lowering drugs cholestyramine on serum LDL levels and endothelium-dependent relaxation to acetylcholine (ACh) in cholesterol-fed or streptozotocin (STZ)-induced diabetic mice. 2. In aortic rings from control mice, ACh or A23187 caused concentration-dependent relaxation. The relaxations caused by ACh or A23187 were significantly attenuated in aortic rings from cholesterol-fed and STZ-diabetic mice. The attenuated vasodilatation in both cholesterol-fed and diabetic mice was returned to normal by chronic administration of cholestyramine. The endothelium-independent relaxations of aortic rings induced by sodium nitroprusside (SNP) were not significantly different between control, cholesterol-fed and STZ-induced diabetic mice. 3. The increased LDL levels in cholesterol-fed and diabetic mice were returned to normal by the chronic administration of cholestyramine. Chronic administration of cholestyramine had no effects on serum glucose levels. 4. These results suggest that attenuated endothelium-dependent vasodilatations in both cholesterol-fed and STZ-diabetic mice are improved by the chronic administration of cholestyramine, and these effects are, at least in part, due to lowering serum LDL levels. PMID:8735642

  11. Natural product extract of Dicksonia sellowiana induces endothelium-dependent relaxations by a redox-sensitive Src- and Akt-dependent activation of eNOS in porcine coronary arteries.

    PubMed

    Rattmann, Yanna D; Anselm, Eric; Kim, Jong-Hun; Dal-Ros, Stéphanie; Auger, Cyril; Miguel, Obdulio G; Santos, Adair R S; Chataigneau, Thierry; Schini-Kerth, Valérie B

    2012-01-01

    The consumption of polyphenol-rich food is associated with a decreased mortality from coronary diseases. This study examined whether a standardized hydroalcoholic extract of Dicksonia sellowiana (HEDS) triggered endothelium-dependent relaxations in porcine coronary artery rings and characterized the underlying mechanism. The phosphorylation level of Src, Akt and eNOS was assessed by Western blot analysis, the formation of reactive oxygen species by dihydroethidine staining and the level of eNOS Ser1177 phosphorylation by immunohistochemical staining in sections of coronary arteries. HEDS-induced endothelium-dependent relaxations were strongly reduced by Nω-nitro-L-arginine, an eNOS inhibitor, and by its combination with charybdotoxin plus apamin, inhibitors of endothelium-derived hyperpolarizing factor-mediated responses. These relaxations were markedly reduced by MnTMPyP (a membrane-permeant mimetic of superoxide dismutase), polyethylene glycol catalase (PEG-catalase; a membrane-permeant analog of catalase), and by wortmannin (an inhibitor of PI3-kinase). HEDS-induced sustained phosphorylation of Akt and eNOS in endothelial cells was abolished by MnTMPyP, PEG-catalase and wortmannin. Oral administration of HEDS induced a significant decrease of mean arterial pressure in spontaneously hypertensive rats. These findings indicate that HEDS caused endothelium-dependent relaxations of coronary artery rings through the redox-sensitive activation of the endothelial PI3-kinase/Akt pathway leading to the subsequent activation of eNOS by phosphorylation. HEDS also has antihypertensive properties. Copyright © 2012 S. Karger AG, Basel.

  12. Kaempferol enhances endothelium-dependent relaxation in the porcine coronary artery through activation of large-conductance a2+-activated K+ channels

    PubMed Central

    Xu, Y C; Leung, S W S; Leung, G P H; Man, R Y K

    2015-01-01

    Background and Purpose Kaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone. The present study aimed to elucidate the signalling pathway through which this flavonoid enhanced relaxation of vascular smooth muscle. Experimental Approach The effect of kaempferol on the relaxation of porcine coronary arteries to endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) relaxing agents was studied in an in vitro organ chamber setup. The whole-cell patch-clamp technique was used to determine the effect of kaempferol on potassium channels in porcine coronary artery smooth muscle cells (PCASMCs). Key Results At a concentration without direct effect on vascular tone, kaempferol (3 × 10−6 M) enhanced relaxations produced by bradykinin and sodium nitroprusside. The potentiation by kaempferol of the bradykinin-induced relaxation was not affected by Nω-nitro-L-arginine methyl ester, an inhibitor of NO synthase (10−4 M) or TRAM-34 plus UCL 1684, inhibitors of intermediate- and small-conductance calcium-activated potassium channels, respectively (10−6 M each), but was abolished by tetraethylammonium chloride, a non-selective inhibitor of calcium-activated potassium channels (10−3 M), and iberiotoxin, a selective inhibitor of large-conductance calcium-activated potassium channel (KCa1.1; 10−7 M). Iberiotoxin also inhibited the potentiation by kaempferol of sodium nitroprusside-induced relaxations. Kaempferol stimulated an outward-rectifying current in PCASMCs, which was abolished by iberiotoxin. Conclusions and Implications The present results suggest that, in smooth muscle cells of the porcine coronary artery, kaempferol enhanced relaxations caused by endothelium-derived and exogenous NO as well as those due to endothelium-dependent hyperpolarization. This vascular effect of kaempferol involved the activation of KCa1.1 channels. PMID:25652142

  13. Reactive oxygen species-induced impairment of endothelium-dependent relaxations in rat aortic rings: protection by methanolic extracts of Phoebe grandis.

    PubMed

    Yeh-Siang, Lau; Subramaniam, Gopal; Hadi, A Hamid A; Murugan, Dharmani; Mustafa, Mohd Rais

    2011-04-06

    Generation of reactive oxygen species plays a pivotal role in the development of cardiovascular diseases. The present study describes the effects of the methanolic extract of Phoebe grandis (MPG) stem bark on reactive oxygen species-induced endothelial dysfunction in vitro. Endothelium-dependent (acetylcholine, ACh) and -independent relaxation (sodium nitroprusside, SNP) was investigated from isolated rat aorta of Sprague-Dawley (SD) in the presence of the β-NADH (enzymatic superoxide inducer) and MPG extract. Superoxide anion production in aortic vessels was measured by lucigen chemiluminesence. Thirty minutes incubation of the rat aorta in vitro with β-NADH increased superoxide radical production and significantly inhibited ACh-induced relaxations. Pretreatment with MPG (0.5, 5 and 50 μg/mL) restored the ACh-induced relaxations (R(max): 92.29% ± 2.93, 91.02% ± 4.54 and 88.31 ± 2.36, respectively) in the presence of β-NADH. MPG was ineffective in reversing the impaired ACh-induced relaxations caused by pyrogallol, a non-enzymatic superoxide generator. Superoxide dismutase (a superoxide scavenger), however, reversed the impaired ACh relaxations induced by both β-NADH and pyrogallol. MPG also markedly inhibited the β-NADH-induced generation of the superoxide radicals. Furthermore, MPG scavenging peroxyl radicals generated by tBuOOH (10⁻⁴ M).These results indicate that MPG may improve the endothelium dependent relaxations to ACh through its scavenging activity as well as by inhibiting the NADH/NADPH oxidase induced generation of superoxide anions.

  14. Crataegus special extract WS 1442 causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of endothelial NO synthase but not via activation of estrogen receptors.

    PubMed

    Anselm, Eric; Socorro, Vanesca Frota Madeira; Dal-Ros, Stéphanie; Schott, Christa; Bronner, Christian; Schini-Kerth, Valérie B

    2009-03-01

    This study determined whether the Crataegus (Hawthorn species) special extract WS 1442 stimulates the endothelial formation of nitric oxide (NO), a vasoprotective factor, and characterized the underlying mechanism. Vascular reactivity was assessed in porcine coronary artery rings, reactive oxygen species (ROS) formation in artery sections by microscopy, and phosphorylation of Akt and endothelial NO synthase (eNOS) in endothelial cells by Western blot analysis. WS 1442 caused endothelium-dependent relaxations in coronary artery rings, which were reduced by N-nitro-L-arginine (a competitive inhibitor of NO synthase) and by charybdotoxin plus apamin (two inhibitors of endothelium-derived hyperpolarizing factor-mediated responses). Relaxations to WS 1442 were inhibited by intracellular ROS scavengers and inhibitors of Src and PI3-kinase, but not by an estrogen receptor antagonist. WS 1442 stimulated the endothelial formation of ROS in artery sections, and a redox-sensitive phosphorylation of Akt and eNOS in endothelial cells. WS 1442 induced endothelium-dependent NO-mediated relaxations of coronary artery rings through the redox-sensitive Src/PI3-kinase/Akt-dependent phosphorylation of eNOS.

  15. Chicago sky blue and a helium neon laser abolish endothelium dependent relaxation in vivo in the microcirculation

    SciTech Connect

    Nishimura, H.; Nelson, G.H.; Rosenblum, W.I. )

    1989-12-01

    Chicago sky blue, also known as Niagara sky blue, is a vital dye that can successfully be used as an intravascular energy absorbing target for the light from a helium-neon (HeNe) laser. The result of this light/dye interaction is endothelium damage which can be controlled by adjusting the duration of the laser exposure and the amount of dye injected intravenously. The endothelial damage probably is the result of the heat generated by the dyes absorption of energy at the interface between plasma and endothelium. The most minimal damage resulted in selective loss of the dilation normally produced by acetylcholine and bradykinin, two endothelium dependent dilators. The dilation produced by sodium nitroprusside, a dilator acting directly on vascular smooth muscle, was preserved. More severe injury (i.e. more prolonged exposure to light and/or more dye), resulted in local platelet aggregation at the site of laser impact.

  16. Chicago sky blue and a helium neon laser abolish endothelium dependent relaxation in vivo in the microcirculation.

    PubMed

    Nishimura, H; Nelson, G H; Rosenblum, W I

    1989-12-01

    Chicago sky blue, also known as Niagara sky blue, is a vital dye that can successfully be used as an intravascular energy absorbing target for the light from a helium-neon (HeNe) laser. The result of this light/dye interaction is endothelium damage which can be controlled by adjusting the duration of the laser exposure and the amount of dye injected intravenously. The endothelial damage probably is the result of the heat generated by the dyes absorption of energy at the interface between plasma and endothelium. The most minimal damage resulted in selective loss of the dilation normally produced by acetylcholine and bradykinin, two endothelium dependent dilators. The dilation produced by sodium nitroprusside, a dilator acting directly on vascular smooth muscle, was preserved. More severe injury (i.e. more prolonged exposure to light and/or more dye, resulted in local platelet aggregation at the site of laser impact.

  17. Endothelium-dependent responses in coronary arteries are changed with puberty in male pigs.

    PubMed

    Chatrath, Ritu; Ronningen, Karen L; Severson, Sandra R; LaBreche, Peter; Jayachandran, Muthuvel; Bracamonte, Margarita P; Miller, Virginia M

    2003-09-01

    In humans, cardiovascular disease begins in young adulthood and is more prevalent in males than females. However, little is known about vascular function during transition to adulthood in males. The aim of this study was to define changes in production of endothelium-derived nitric oxide (NO) and coronary arterial responses during puberty. Plasma was collected from juvenile (2-3 mo of age) and adult (5-6 mo of age) male pigs (n = 8/group) for measurement of NO, and aortic endothelial cells were collected for measurement of mRNA and protein for endothelial NO synthase (eNOS). Although plasma NO was higher in juvenile (67.0 +/- 25.6 microM) than in adult (15.0 +/- 7.1 microM) male pigs, eNOS protein was similar in both groups. However, levels of mRNA for eNOS were lower in aortic endothelial cells from juvenile pigs. In rings of coronary arteries suspended in organ chambers for measurement of isometric force and contracted with PGF2alpha, relaxations to an alpha2-adrenergic agonist were significantly inhibited by indomethacin only in juvenile pigs [EC50 (-log M), 6.7 +/- 0.3 with indomethacin and 7.7 +/- 0.3 under control conditions]. NG-monomethyl-l-arginine (l-NMMA) inhibited relaxations in both groups. On the contrary, in the presence of indomethacin, relaxations to bradykinin were inhibited by l-NMMA only in arteries from adult pigs [EC50 (-log M), 8.9 +/- 0.3 with indomethacin and 8.6 +/- 0.3 with addition of l-NMMA]. These results suggest that hormonal changes associated with sexual maturity may affect posttranscriptional and/or translational regulation of eNOS protein and result in lower plasma NO in adult male pigs. In addition, endothelium-derived inhibitory cyclooxygenase products seem to predominate in juveniles.

  18. Betulinic acid ameliorates endothelium-dependent relaxation in L-NAME-induced hypertensive rats by reducing oxidative stress.

    PubMed

    Fu, Jia-Yin; Qian, Ling-Bo; Zhu, Lie-Gang; Liang, Hao-Te; Tan, Yi-Nuo; Lu, Han-Ti; Lu, Jian-Feng; Wang, Hui-Ping; Xia, Qiang

    2011-10-09

    Zizyphi Spinosi semen (ZSS) is one of the most widely used traditional Chinese herbs with protective effects on the cardiovascular system. It is not clear whether betulinic acid (BA), the key active constituent of ZSS, has beneficial cardiovascular effects on N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. The objective of this study was to investigate the effect of BA on endothelium-dependent vasorelaxation in isolated aortic rings from L-NAME-induced hypertensive rats and its underlying mechanisms. Male Sprague-Dawley rats were injected with L-NAME (15 mg/kg/d, i.p.) for 4 weeks to induce hypertension. After treatment with L-NAME for 2 weeks, rats with mean blood pressure >120 mm Hg measured by tail-cuff method were considered hypertensive and then injected with BA (0.8, 4, 20 mg/kg/d, i.p.) for the last 2 weeks. The effect of BA on the tension of rat thoracic aortic rings was measured in an organ bath system. The levels of nitric oxide (NO), reactive oxygen species (ROS), and the activity of superoxide dismutase (SOD) and nitric oxide synthase (NOS) in aortas were assayed. We found that BA (0.1-100 μM) evoked a concentration-dependent vasorelaxation in endothelium-intact normal rat aortic rings, which was significantly attenuated by pretreatment with L-NAME (100 μM) or methylene blue (MB, 10 μM), but not by indomethacin (10 μM). Pretreatment with EC(50) (1.67 μM) concentration of BA enhanced the acetylcholine (ACh)-induced vasorelaxation, which was also markedly reversed by both L-NAME and MB. The blood pressure in hypertensive rats increased to 135.22±5.38 mm Hg (P<0.01 vs. control group), which was markedly attenuated by high dose of BA. The ACh-induced vasorelaxation in hypertensive rat aortic rings was impaired, which was markedly improved by chronic treatment with BA (20 mg/kg/d) for 2 weeks. The increase of ROS level and the decrease of NO level, SOD and eNOS activities in hypertensive rat aortas were all

  19. The ent-15α-Acetoxykaur-16-en-19-oic Acid Relaxes Rat Artery Mesenteric Superior via Endothelium-Dependent and Endothelium-Independent Mechanisms

    PubMed Central

    Ribeiro, Êurica Adélia Nogueira; Herculano, Edla de Azevedo; da Costa, Cintia Danieli Ferreira; Furtado, Fabiola Fialho; da-Cunha, Emídio Vasconcelos Leitão; Barbosa-Filho, José Maria; da Silva, Marcelo Sobral; de Medeiros, Isac Almeida

    2012-01-01

    The objective of the study was to investigate the mechanism of the relaxant activity of the ent-15α-acetoxykaur-16-en-19-oic acid (KA-acetoxy). In rat mesenteric artery rings, KA-acetoxy induced a concentration-dependent relaxation in vessels precontracted with phenylephrine. In the absence of endothelium, the vasorelaxation was significantly shifted to the right without reduction of the maximum effect. Endothelium-dependent relaxation was significantly attenuated by pretreatment with L-NAME, an inhibitor of the NO-synthase (NOS), indomethacin, an inhibitor of the cyclooxygenase, L-NAME + indomethacin, atropine, a nonselective antagonist of the muscarinic receptors, ODQ, selective inhibitor of the guanylyl cyclase enzyme, or hydroxocobalamin, a nitric oxide scavenger. The relaxation was completely reversed in the presence of L-NAME + 1 mM L-arginine or L-arginine, an NO precursor. Diterpene-induced relaxation was not affected by TEA, a nonselective inhibitor of K+ channels. The KA-acetoxy antagonized CaCl2-induced contractions in a concentration-dependent manner and also inhibited an 80 mM KCl-induced contraction. The KA-acetoxy did not interfere with Ca2+ release from intracellular stores. The vasorelaxant induced by KA-acetoxy seems to involve the inhibition of the Ca2+ influx and also, at least in part, by endothelial muscarinic receptors activation, NO and PGI2 release. PMID:23346202

  20. Endothelium-dependent relaxation and noradrenaline sensitivity in mesenteric resistance arteries of streptozotocin-induced diabetic rats.

    PubMed Central

    Taylor, P. D.; McCarthy, A. L.; Thomas, C. R.; Poston, L.

    1992-01-01

    1. Noradrenaline sensitivity and acetylcholine-induced relaxation were investigated in mesenteric resistance arteries of control and streptozotocin-induced diabetic rats. 2. The diabetic rats demonstrated enhanced vascular sensitivity to noradrenaline compared with age-matched controls (pEC50 5.99 +/- 0.06 for diabetic rats, n = 25, versus 5.82 +/- 0.03 for controls, n = 45, P < 0.05). 3. Significant impairment of acetylcholine-induced relaxation was observed in arteries from the diabetic animals compared with controls (pEC50 6.81 +/- 0.17 for diabetic rats, n = 21, versus 7.54 +/- 0.17 for controls, n = 45, P < 0.001). 4. The difference between acetylcholine-induced relaxation in diabetic and control arteries remained in the presence of 10 microM indomethacin (pEC50 6.41 +/- 0.11 for diabetic rats, n = 16, versus 7.59 +/- 0.08 for controls, n = 20, P < 0.001). 5. The nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA, 1 mM) produced profound inhibition of acetylcholine-induced relaxation in diabetic arteries but partial inhibition in controls. The incomplete inhibition of acetylcholine-induced relaxation by L-NMMA in the control arteries was the result of ineffective inhibition of nitric oxide synthase since an alternative inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM), led to similar inhibition to that seen in the diabetic arteries with L-NMMA. The endothelium-derived relaxing factor (EDRF)-mediated component of acetylcholine-induced relaxation determined by use of the nitric oxide synthase inhibitors was, therefore, apparently reduced in diabetic rats compared with control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1422588

  1. Interleukin-6 impairs endothelium-dependent NO-cGMP-mediated relaxation and enhances contraction in systemic vessels of pregnant rats.

    PubMed

    Orshal, Julia M; Khalil, Raouf A

    2004-06-01

    IL-6 is elevated in plasma of preeclamptic women, and twofold elevation of plasma IL-6 increases vascular resistance and arterial pressure in pregnant rats, suggesting a role of the cytokine in hypertension of pregnancy. However, whether the hemodynamic effects of IL-6 reflect direct effects of the cytokine on the mechanisms of vascular contraction/relaxation is unclear. The purpose of this study was to test the hypothesis that IL-6 directly impairs endothelium-dependent relaxation and enhances vascular contraction in systemic vessels of pregnant rats. Active stress was measured in aortic strips isolated from virgin and late pregnant Sprague-Dawley rats and then nontreated or treated for 1 h with IL-6 (10 pg/ml to 10 ng/ml). In endothelium-intact vascular strips, phenylephrine (Phe, 10(-5) M) caused an increase in active stress that was smaller in pregnant (4.2 +/- 0.3) than virgin rats (5.1 +/- 0.3 x 10(4) N/m(2)). IL-6 (1,000 pg/ml) caused enhancement of Phe contraction that was greater in pregnant (10.6 +/- 0.7) than virgin rats (7.5 +/- 0.4 x 10(4) N/m(2)). ACh and bradykinin caused relaxation of Phe contraction and increases in vascular nitrite production that were greater in pregnant than virgin rats. IL-6 caused reductions in ACh- and bradykinin-induced vascular relaxation and nitrite production that were more prominent in pregnant than virgin rats. Incubation of endothelium-intact strips in the presence of N(omega)-nitro-L-arginine methyl ester (10(-4) M) to inhibit nitric oxide (NO) synthase, or 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 10(-5) M) to inhibit cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe-induced stress in nontreated but to a lesser extent in IL-6-treated vessels, particularly those of pregnant rats. Removal of the endothelium enhanced Phe-induced stress in nontreated but not IL-6-treated vessels, particularly those of pregnant rats. In endothelium-denuded strips, relaxation of Phe contraction with

  2. Tocotrienol Rich Palm Oil Extract Is More Effective Than Pure Tocotrienols at Improving Endothelium-Dependent Relaxation in the Presence of Oxidative Stress

    PubMed Central

    Ali, Saher F.; Woodman, Owen L.

    2015-01-01

    Oxidative endothelial dysfunction is a critical initiator of vascular disease. Vitamin E is an effective antioxidant but attempts to use it to treat vascular disorders have been disappointing. This study investigated whether tocotrienols, the less abundant components of vitamin E compared to tocopherols, might be more effective at preserving endothelial function. Superoxide generated by hypoxanthine/xanthine oxidase or rat aorta was measured using lucigenin-enhanced chemiluminescence. The effect of α-tocopherol, α-, δ-, and γ-tocotrienols and a tocotrienol rich palm oil extract (tocomin) on levels of superoxide was assessed. Endothelial function in rat aorta was assessed in the presence of the auto-oxidant pyrogallol. Whilst all of the compounds displayed antioxidant activity, the tocotrienols were more effective when superoxide was produced by hypoxanthine/xanthine oxidase whereas tocomin and α-tocopherol were more effective in the isolated aorta. Tocomin and α-tocopherol restored endothelial function in the presence of oxidant stress but α-, δ-, and γ-tocotrienols were ineffective. The protective effect of tocomin was replicated when the tocotrienols were present with, but not without, α-tocopherol. Tocotrienol rich tocomin is more effective than α-tocopherol at reducing oxidative stress and restoring endothelium-dependent relaxation in rat aortae and although α-, δ-, and γ-tocotrienols effectively scavenged superoxide, they did not improve endothelial function. PMID:26075031

  3. Beneficial Effects of Calcitriol on Hypertension, Glucose Intolerance, Impairment of Endothelium-Dependent Vascular Relaxation, and Visceral Adiposity in Fructose-Fed Hypertensive Rats

    PubMed Central

    Chou, Chu-Lin; Pang, Cheng-Yoong; Lee, Tony J. F.; Fang, Te-Chao

    2015-01-01

    Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose

  4. Endothelium dependency of contractile activity differs in infant and adult vertebral arteries.

    PubMed Central

    Charpie, J R; Schreur, K D; Papadopoulos, S M; Webb, R C

    1994-01-01

    Contractions to serotonin (5-HT) and endothelin-1 (ET-1) in infant (0-2 yr) and adult (38-71 yr) vertebral arteries were examined in the presence of either the cyclooxygenase inhibitor indomethacin or NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide production. In addition, endothelium-dependent relaxations to acetylcholine were characterized in arteries contracted with agonist. The results showed that: (a) Contractions of infant arteries to 5-HT or ET-1 decreased to 44 +/- 8% and 27 +/- 13%, respectively, within 10 min. Indomethacin or removal of endothelium abolished this decreased response, whereas L-NMMA had no effect. (b) Adult arteries produced sustained contractions to 5-HT or ET-1 that were unaffected by indomethacin, endothelium denudation, or L-NMMA. (c) Endothelium-dependent relaxations to acetylcholine were greater in infant than adult arteries and were abolished by indomethacin (but not L-NMMA) in infants and L-NMMA (but not indomethacin) in adults. Thus, endothelium-dependent responses in infant arteries are attenuated because of increased prostaglandin activity not observed in adult tissues. Additionally, there is an age-dependent change in the primary mechanism responsible for acetylcholine-induced vasodilation. Apparently, endothelium dependency of acetylcholine-induced relaxation is highly dependent on cyclooxygenase activity in the infant vertebral artery, but in the adult artery, nitric oxide is linked to the vasodilator response. Images PMID:8132776

  5. A chemically defined 2,3-trans procyanidin fraction from willow bark causes redox-sensitive endothelium-dependent relaxation in porcine coronary arteries.

    PubMed

    Kaufeld, Aurica M; Pertz, Heinz H; Kolodziej, Herbert

    2014-07-25

    Extracts of the bark of willow species (Salix spp.) are popular herbal remedies to relieve fever and inflammation. The effects are attributed to salicin and structurally related phenolic metabolites, while polyphenols including procyanidins are suggested to contribute to the overall effect of willow bark. This study aimed at investigating the relaxant response to a highly purified and chemically defined 2,3-trans procyanidin fraction in porcine coronary arteries. The procyanidin sample produced a concentration-dependent relaxation in U46619-precontracted tissues. Relaxation was predominantly mediated through the redox-sensitive activation of the endothelial phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway, leading to the subsequent activation of endothelial nitric oxide synthase (eNOS) by phosphorylation, as evidenced by Western blotting using human umbilical vein endothelial cells (HUVECs). That the relaxant response to Salix procyanidins was reactive oxygen species (ROS)-dependent with O2(-) as the key species followed from densitometric analysis using 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA assay) and employment of various ROS inhibitors, respectively. The data also suggested the modification of intracellular Ca(2+) levels and KCa channel functions. In addition, our organ bath studies showed that Salix procyanidins reversed the abrogation of the relaxant response to bradykinin by oxidized low-density lipoproteins (oxLDL) in coronary arteries, suggesting a vasoprotective effect of willow bark against detrimental oxLDL in pathological conditions. Taken together, our findings suggest for the first time that 2,3-trans procyanidins may contribute not only to the beneficial effects of willow bark but also to health-promoting benefits of diverse natural products of plant origin.

  6. An ethanolic extract of Lindera obtusiloba stems causes NO-mediated endothelium-dependent relaxations in rat aortic rings and prevents angiotensin II-induced hypertension and endothelial dysfunction in rats.

    PubMed

    Lee, Jung-Ok; Oak, Min-Ho; Jung, Sang Hoon; Park, Dong Hyun; Auger, Cyril; Kim, Kyoung Rak; Lee, Seung-Woo; Schini-Kerth, Valérie B

    2011-06-01

    Lindera obtusiloba is a medical herb traditionally used in Asia for the improvement of blood circulation, treatment of inflammation, and prevention of liver damage. The possibility that L. obtusiloba affects vascular reactivity remains to be examined. Therefore, the aim of the present study was to evaluate both the in vitro and in vivo vascular effects of an ethanolic extract of L. obtusiloba stems (LOE). Vascular reactivity was assessed in organ chambers using rat aortic rings and the activation of endothelial NO synthase (eNOS) in cultured bovine aortic endothelial cells. LOE induced endothelium-dependent relaxations, which were abolished by inhibitors of nitric oxide synthase (N (ω)-nitro-L: -arginine) and guanylyl cyclase (1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-L-one), significantly reduced by inhibitors of PI3 kinase (wortmannin and LY294002), and not affected by inhibitors of cyclooxygenase (indomethacin) and endothelium-derived hyperpolarizing factor-mediated responses (charybdotoxin plus apamin). LOE prevented contractile responses to phenylephrine and angiotensin II in rings with endothelium, but not in those without endothelium. LOE caused a concentration-dependent phosphorylation of Akt at Serine473 and eNOS at Serine1177 in endothelial cells. Thereafter, the vasoprotective effect of LOE was investigated in an experimental model of hypertension in rats. Intake of LOE prevented the angiotensin II-induced increase in systolic blood pressure, and endothelial dysfunction to acetylcholine and oxidative stress as assessed using dihydroethidine in aortic rings. The present findings indicate that LOE has vasoprotective and antihypertensive properties most likely by stimulating the endothelial formation of NO and inhibiting oxidative stress.

  7. Participation of K+ channels in the endothelium-dependent and endothelium-independent components of the relaxant effect of rosuvastatin in rat aortic rings.

    PubMed

    López, Jorge; Mendoza, Roberto; Cleva Villanueva, Guadalupe; Martínez, Gustavo; Castillo, Enrique F; Castillo, Carlos

    2008-09-01

    Rosuvastatin was tested on rat aortic rings in the presence and absence of K(+) channel blockers, mevalonic acid, and inhibitors of nitric oxide, prostaglandins, or endothelial-derived hyperpolarizing factor synthesis. The direct vascular effects of rosuvastatin were then evaluated by obtaining dose-response curves. Rosuvastatin relaxed aortic rings with and, to a lesser degree, without endothelium. Under both these conditions this effect was partially inhibited by L-NAME, tetraethylammonium, apamin + charybdotoxin (only administered together), or mevalonic acid. The combination of L-NAME with any of the other 3 treatments completely inhibited the effect of rosuvastatin, but indomethacin, clotrimazol, glibenclamide, charybdotoxin, or apamin alone had no effect. Therefore, the relaxation induced by rosuvastatin, even in the absence of endothelium, is partially related to 2 different mechanisms, one that is isoprenoid dependent and NO mediated and the other that is tied to the opening of Ca( 2+)-dependent K(+) channels of the slow subfamily.

  8. Potentiation of vasoconstrictor response and inhibition of endothelium-dependent vasorelaxation by gallic acid in rat aorta.

    PubMed

    Sanae, Fujiko; Miyaichi, Yukinori; Hayashi, Hisao

    2002-08-01

    In the isolated rat thoracic aorta, gallic acid potentiated the vasoconstrictor response to phenylephrine. The potentiation produced by gallic acid was absent in endothelium-denuded arteries. The potentiation was abolished by N(G)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis, and slightly attenuated by an addition of L-arginine, while indomethacin or BQ610 had no effect. The potentiation of response to phenylephrine was not found for structural modifications of gallic acid, except for caffeic acid. Gallic acid also inhibited vasorelaxation induced by acetylcholine, sodium nitroprusside or prostacyclin, especially that by acetylcholine. The effect on vasorelaxation induced by acetylcholine was decreased by esterification of the carboxy group of gallic acid, and in the absence or by the methylation of the o-dihydroxy group. Caffeic acid inhibited the vasorelaxation, though the effect was smaller than that of gallic acid. These findings indicate that gallic acid produces a potentiation of contractile response and inhibition of vasorelaxant responses, probably through inactivation of nitric oxide (NO), in which endothelially produced NO is principally involved, and that the modification of functional groups of the gallic acid molecule abolishes the potentiation of contractile response and attenuates the inhibition of vasorelaxant responses.

  9. Suppression of endoplasmic reticulum stress improves endothelium-dependent contractile responses in aorta of the spontaneously hypertensive rat

    PubMed Central

    Matsumoto, Takayuki; Webb, R. Clinton

    2013-01-01

    A contributing factor to increased peripheral resistance seen during hypertension is an increased production of endothelium-derived contractile factors (EDCFs). The main EDCFs are vasoconstrictor prostanoids, metabolites of arachidonic acid (AA) produced by Ca2+-dependent cytosolic phospholipase A2 (cPLA2) following phosphorylation (at Ser505) mediated by extracellular signal-regulated kinase (ERK1/2) and cyclooxygenase (COX) activations. Although endoplasmic reticulum (ER) stress has been shown to contribute to pathophysiological alterations in cardiovascular diseases, the relationship between ER stress and EDCF-mediated responses remains unclear. We tested the hypothesis that ER stress plays a role in EDCF-mediated responses via activation of the cPLA2/COX pathway in the aorta of the spontaneously hypertensive rat (SHR). Male SHR and Wistar-Kyoto rats (WKY) were treated with ER stress inhibitor, tauroursodeoxycholic acid or 4-phenlybutyric acid (TUDCA or PBA, respectively, 100 mg·kg−1·day−1 ip) or PBS (control, 300 μl/day ip) for 1 wk. There was a decrease in systolic blood pressure in SHR treated with TUDCA or PBA compared with control SHR (176 ± 3 or 181 ± 5, respectively vs. 200 ± 2 mmHg). In the SHR, treatment with TUDCA or PBA normalized aortic (vs. control SHR) 1) contractions to acetylcholine (ACh), AA, and tert-butyl hydroperoxide, 2) ACh-stimulated releases of prostanoids (thromboxane A2, PGF2α, and prostacyclin), 3) expression of COX-1, 4) phosphorylation of cPLA2 and ERK1/2, and 5) production of H2O2. Our findings demonstrate a novel interplay between ER stress and EDCF-mediated responses in the aorta of the SHR. Moreover, ER stress inhibition normalizes such responses by suppressing the cPLA2/COX pathway. PMID:23709602

  10. Suppression of endoplasmic reticulum stress improves endothelium-dependent contractile responses in aorta of the spontaneously hypertensive rat.

    PubMed

    Spitler, Kathryn M; Matsumoto, Takayuki; Webb, R Clinton

    2013-08-01

    A contributing factor to increased peripheral resistance seen during hypertension is an increased production of endothelium-derived contractile factors (EDCFs). The main EDCFs are vasoconstrictor prostanoids, metabolites of arachidonic acid (AA) produced by Ca(2+)-dependent cytosolic phospholipase A2 (cPLA2) following phosphorylation (at Ser(505)) mediated by extracellular signal-regulated kinase (ERK1/2) and cyclooxygenase (COX) activations. Although endoplasmic reticulum (ER) stress has been shown to contribute to pathophysiological alterations in cardiovascular diseases, the relationship between ER stress and EDCF-mediated responses remains unclear. We tested the hypothesis that ER stress plays a role in EDCF-mediated responses via activation of the cPLA2/COX pathway in the aorta of the spontaneously hypertensive rat (SHR). Male SHR and Wistar-Kyoto rats (WKY) were treated with ER stress inhibitor, tauroursodeoxycholic acid or 4-phenlybutyric acid (TUDCA or PBA, respectively, 100 mg·kg(-1)·day(-1) ip) or PBS (control, 300 μl/day ip) for 1 wk. There was a decrease in systolic blood pressure in SHR treated with TUDCA or PBA compared with control SHR (176 ± 3 or 181 ± 5, respectively vs. 200 ± 2 mmHg). In the SHR, treatment with TUDCA or PBA normalized aortic (vs. control SHR) 1) contractions to acetylcholine (ACh), AA, and tert-butyl hydroperoxide, 2) ACh-stimulated releases of prostanoids (thromboxane A2, PGF2α, and prostacyclin), 3) expression of COX-1, 4) phosphorylation of cPLA2 and ERK1/2, and 5) production of H2O2. Our findings demonstrate a novel interplay between ER stress and EDCF-mediated responses in the aorta of the SHR. Moreover, ER stress inhibition normalizes such responses by suppressing the cPLA2/COX pathway.

  11. Hyperoxic gassing with Tiron enhances bradykinin-induced endothelium-dependent and EDH-type relaxation through generation of hydrogen peroxide.

    PubMed

    Wong, Pui San; Roberts, Richard E; Randall, Michael D

    2015-01-01

    Oxygenation with 95%O2 is routinely used in organ bath studies. However, hyperoxia may affect tissue responses, particularly in studies which involve reactive oxygen species (ROS). Here, the effects of the antioxidant, Tiron, were investigated under different gassing conditions in the porcine isolated coronary artery (PCA). Distal PCAs from male and female pigs were mounted in a wire myograph gassed with either 95%O2/5%CO2 or 95% air/5%CO2 and pre-contracted with U46619. Concentration-response curves to bradykinin were constructed in the presence of Tiron (1mM), a cell permeable superoxide scavenger and catalase (1000Uml(-1)) to breakdown H2O2. The H2O2 level in Krebs'-Henseleit solution was detected using Amplex Red. Bradykinin produced concentration-dependent vasorelaxations in male and female PCAs when gassed with either 95%O2 or air, with no differences in the Rmax or EC50. Tiron increased the potency of bradykinin only when gassed with 95%O2 in PCAs from both sexes. At 95%O2, catalase prevented the leftward shift caused by Tiron in both sexes indicating that catalase prevented the formation of H2O2 by Tiron. In female PCAs, addition of catalase to Tiron significantly reduced the Rmax. In the EDH-type response (using L-NAME and indomethacin), Tiron enhanced the potency of the bradykinin-induced vasorelaxation when gassed with 95%O2 in PCAs from both sexes. Biochemical analysis using Amplex Red demonstrated that H2O2 was generated in Krebs'-Henseleit solution when gassed with 95%O2, but not with air. Therefore, hyperoxic gassing conditions could alter the environment generating superoxide within the Krebs'-Henseleit buffer, which may, in turn, influence the in vitro pharmacological responses.

  12. Endothelium-dependent contraction of rat thoracic aorta induced by gallic acid.

    PubMed

    Sanae, Fujiko; Miyaichi, Yukinori; Hayashi, Hisao

    2003-02-01

    The vascular effect of a component of hydrolysable tannins, gallic acid, was examined in isolated rat thoracic aorta. Gallic acid exerted a contractile effect on the phenylephrine- or prostaglandin F(2/alpha)-precontracted endothelium-intact arteries. In endothelium-denuded arteries, the contractile response to-gallic acid was absent. Pretreatment with N(G)-nitro-L-arginine methyl ester (30 microM) abolished the gallic acid-induced contraction. Pretreatment with indomethacin (10 microM) or BQ610 (100 nM) had no observed effect. Pretreatment with gallic acid (1-10 microM) significantly attenuated the relaxation induced by acetylcholine, and that with 10 microM gallic acid also reduced the potency of sodium nitroprusside in the relaxation, without a reduction in efficacy, in endothelium-denuded arteries. These findings indicate that gallic acid induced endothelium-dependent contraction and strongly inhibited the endothelium-dependent relaxation rather than the endothelium-independent relaxation, probably through inhibition of endothelial nitric oxide (NO) production. Since NO plays an important role in vasodilative regulation and inflammatory disorders, these findings may also indicate that gallic acid interferes with the inflammatory responses.

  13. Association and cosegregation of stroke with impaired endothelium-dependent vasorelaxation in stroke prone, spontaneously hypertensive rats.

    PubMed Central

    Volpe, M; Iaccarino, G; Vecchione, C; Rizzoni, D; Russo, R; Rubattu, S; Condorelli, G; Ganten, U; Ganten, D; Trimarco, B; Lindpaintner, K

    1996-01-01

    While hypertension is a major risk factor for stroke, it is not its sole determinant. Despite similar blood pressures, spontaneously hypertensive rats (SHR) do not share the predisposition to cerebrovascular disease typical of stroke-prone spontaneously hypertensive rats (SHRSP). We investigated vascular function in male SHR and SHRSP as well as in SHRSP/SHR-F2 hybrid animals. Animals were maintained on the appropriate dietary regimen necessary for the manifestation of stroke. Among the hybrid animals, a group of stroke-prone and a group of stroke-resistant rats were selected. Blood pressure was similar in all groups. Endothelium-independent vascular reactivity tested on isolated rings of thoracic aorta and basilar artery after death showed similar contractile and dilatory responses to serotonin and nitroglycerin, respectively, in all groups. In contrast, endothelium-dependent relaxation, in response to acetylcholine or substance P, was markedly reduced in SHRSP compared with SHR. Similarly, reduced vasodilatory responses were present in aortae of F2 rats that had suffered a stroke when compared with SHR or F2 rats resistant to stroke. The observed association and cosegregation of stroke with significant and specific impairment of endothelium-dependent vasorelaxation among SHRSP and stroke-prone F2 hybrids, respectively, suggest a potential causal role of altered endothelium-dependent vascular relaxation in the pathogenesis of stroke. PMID:8755632

  14. Impaired endothelium-dependent vasodilation does not initiate the development of sunitinib-associated hypertension.

    PubMed

    Thijs, Anna M J; van Herpen, Carla M L; Verweij, Vivienne; Pertijs, Jeanne; van den Broek, Petra H H; van der Graaf, Winette T A; Rongen, Gerard A

    2015-10-01

    Tyrosine kinase inhibitors targeting angiogenesis have become an important part of the treatment of patients with several types of cancer. One of the most reported side effects of vascular endothelial growth factor receptor (VEGFR)-targeted therapies is hypertension. In this study, we hypothesized that the development of hypertension in patients treated with sunitinib, a multitargeted tyrosine kinase inhibitor, is preceded by reduced endothelium-dependent vasodilation. Moreover, we hypothesized that this endothelial dysfunction is a result of impaired nitric oxide release. In a placebo-controlled experiment, we determined vascular responses in isolated mesenteric arteries of rats (n = 26) after 7 days of sunitinib treatment. Sunitinib reduced endothelium-dependent vasodilation, but not endothelium-independent vasodilation. Moreover, we observed that the difference in endothelium-dependent vasodilation between controls and sunitinib-treated animals disappeared in the presence of N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide antagonist. In patients with metastatic renal cell carcinoma, before and 1 week after start of sunitinib, the endothelium-dependent vasodilator response to intra-arterial acetycholine and the endothelium-independent vasodilator response to intra-arterial sodium nitroprusside was assessed with venous occlusion plethysmography. No changes in forearm blood flow ratios were observed. Mean arterial pressure did significantly increase from 101.9 ± 3.8 to 106.1 ± 2.6 mmHg after 1 week and further to 115.8 (±4.9) mmHg after 2 weeks of treatment. In animals, this study confirms that exposure to high concentrations of sunitinib reduces endothelium-dependent vasodilation by reducing endothelial release of nitric oxide. In humans, however, reduced endothelium-dependent vasodilation does not precede the development of hypertension in patients treated with sunitinib.

  15. EDH: endothelium-dependent hyperpolarization and microvascular signalling.

    PubMed

    Garland, C J; Dora, K A

    2017-01-01

    Endothelium-dependent hyperpolarizing factor (EDHF) is a powerful vasodilator influence in small resistance arteries and thus an important modulator of blood pressure and flow. As the name suggests, EDHF was thought to describe a diffusible factor stimulating smooth muscle hyperpolarization (and thus vasodilatation). However, this idea has evolved with the recognition that a factor can operate alongside the spread of hyperpolarizing current from the endothelium to the vascular smooth muscle (VSM). As such, the pathway is now termed endothelium-dependent hyperpolarization (EDH). EDH is activated by an increase in endothelial [Ca(2+) ]i , which stimulates two Ca(2+) -sensitive K channels, SKCa and IKCa . This was discovered because apamin and charybdotoxin applied in combination blocked EDHF responses, but iberiotoxin - a blocker of BKCa - was not able to substitute for charybdotoxin. SKCa and IKCa channels are arranged in endothelial microdomains, particularly within projections towards the adjacent smooth muscle, which are rich in IKCa channels and close to interendothelial gap junctions where SKCa channels, are prevalent. KCa activation hyperpolarizes endothelial cells, and K(+) efflux through them can act as a diffusible 'EDHF' by stimulating VSM Na(+) ,K(+) -ATPase and inwardly rectifying K channels (KIR ). In parallel, hyperpolarizing current spreads from the endothelium to the smooth muscle through myoendothelial gap junctions located on endothelial projections. The resulting radial EDH is complemented by the spread of 'conducted' hyperpolarization along the endothelium of arteries and arterioles to affect conducted vasodilatation (CVD). Retrograde CVD effectively integrates blood flow within the microcirculation, but how the underlying hyperpolarization is sustained is unclear. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  16. Some electrical properties of the endothelium-dependent hyperpolarization recorded from rat arterial smooth muscle cells.

    PubMed Central

    Chen, G; Suzuki, H

    1989-01-01

    Methylene Blue, ACh and histamine also produced a hyperpolarization similar to that seen in the control. 10. It is concluded that in arteries of the rat, ACh and histamine release a hyperpolarizing substance from the endothelial cells. This substance may be different from the endothelium-derived relaxing factor (EDRF), and is released mainly transiently. The hyperpolarization is generated by an increase in potassium conductance of the membrane, and this has some contribution to the endothelium-dependent relaxation. PMID:2795490

  17. Particulate Matter Exposure Impairs Systemic Microvascular Endothelium-Dependent Dilation

    PubMed Central

    Nurkiewicz, Timothy R.; Porter, Dale W.; Barger, Mark; Castranova, Vincent; Boegehold, Matthew A.

    2004-01-01

    Acute exposure to airborne pollutants, such as solid particulate matter (PM), increases the risk of cardiovascular dysfunction, but the mechanisms by which PM evokes systemic effects remain to be identified. The purpose of this study was to determine if pulmonary exposure to a PM surrogate, such as residual oil fly ash (ROFA), affects endothelium-dependent dilation in the systemic microcirculation. Rats were intratracheally instilled with ROFA at 0.1, 0.25, 1 or 2 mg/rat 24 hr before experimental measurements. Rats intratracheally instilled with saline or titanium dioxide (0.25 mg/rat) served as vehicle or particle control groups, respectively. In vivo microscopy of the spinotrapezius muscle was used to study systemic arteriolar dilator responses to the Ca2+ ionophore A23187, administered by ejection via pressurized micropipette into the arteriolar lumen. We used analysis of bronchoalveolar lavage (BAL) samples to monitor identified pulmonary inflammation and damage. To determine if ROFA exposure affected arteriolar nitric oxide sensitivity, sodium nitroprusside was iontophoretically applied to arterioles of rats exposed to ROFA. In saline-treated rats, A23187 dilated arterioles up to 72 ± 7% of maximum. In ROFA- and TiO2-exposed rats, A23187-induced dilation was significantly attenuated. BAL fluid analysis revealed measurable pulmonary inflammation and damage after exposure to 1 and 2 mg ROFA (but not TiO2 or < 1 mg ROFA), as evidenced by significantly higher polymorphonuclear leukocyte cell counts, enhanced BAL albumin levels, and increased lactate dehydrogenase activity in BAL fluid. The sensitivity of arteriolar smooth muscle to NO was similar in saline-treated and ROFA-exposed rats, suggesting that pulmonary exposure to ROFA affected endothelial rather than smooth muscle function. A significant increase in venular leukocyte adhesion and rolling was observed in ROFA-exposed rats, suggesting local inflammation at the systemic microvascular level. These results

  18. Calcium dobesilate potentiates endothelium-derived hyperpolarizing factor-mediated relaxation of human penile resistance arteries

    PubMed Central

    Angulo, Javier; Cuevas, Pedro; Fernández, Argentina; Gabancho, Sonia; Videla, Sebastián; Tejada, Iñigo Sáenz de

    2003-01-01

    We have evaluated the participation of endothelium-derived hyperpolarizing factor (EDHF) in the endothelium-dependent relaxation of isolated human penile resistance arteries (HPRA) and human corpus cavernosum (HCC) strips. In addition, the effect of the angioprotective agent, calcium dobesilate (DOBE), on the endothelium-dependent relaxation of these tissues was investigated. Combined inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) nearly abolished the endothelium-dependent relaxation to acetylcholine (ACh) in HCC, while 60% relaxation of HPRA was observed under these conditions. Endothelium-dependent relaxation of HPRA resistant to NOS and COX inhibition was prevented by raising the extracellular concentration of K+ (35 mM) or by blocking Ca2+-activated K+ channels, with apamin (APA; 100 nM) and charybdotoxin (CTX; 100 nM), suggesting the involvement of EDHF in these responses. Endothelium-dependent relaxation to ACh was markedly enhanced by DOBE (10 μM) in HPRA but not in HCC. The potentiating effects of DOBE on ACh-induced responses in HPRA, remained after NOS and COX inhibition, were reduced by inhibition of cytochrome P450 oxygenase with miconazole (0.3 mM) and were abolished by high K+ or a combination of APA and CTX. In vivo, DOBE (10 mg kg−1 i.v.) significantly potentiated the erectile responses to cavernosal nerve stimulation in male rats. EDHF plays an important role in the endothelium-dependent relaxation of HPRA but not in HCC. DOBE significantly improves endothelium-dependent relaxation of HPRA mediated by EDHF and potentiates erectile responses in vivo. Thus, EDHF becomes a new therapeutic target for the treatment of erectile dysfunction (ED) and DOBE could be considered a candidate for oral therapy for ED. PMID:12813009

  19. Does endothelium-derived hyperpolarizing factor play a role in endothelium-dependent component of electrical field stimulation-induced vasorelaxation of rat mesenteric arterial rings?

    PubMed

    Ozkan, Melike Hacer; Uma, Serdar

    2009-01-01

    Electrical field stimulation (EFS)-induced, nonadrenergic, noncholinergic vasodilation was investigated in rat mesenteric arterial rings. Tetrodotoxin (10(-6) M), capsaicin (10(-5) M), or L-NAME (10(-4) M) failed to change the EFS-induced relaxations, whereas they were increased with indomethacin (10(-5) M). Removal of the endothelium caused approximately 20% reduction in the maximum response, whereas precontraction with 40 mM KCI abolished the relaxations at all frequencies. Iberiotoxin (3 x 10(-7) M) attenuated the relaxations in endothelium-intact tissues but blocked completely those in endothelium-denuded arteries. Combination of TRAM-34 (10(-5) M) with apamin (5 x 10(-7) M) and single administrations of NiCI2 (5 x 10(-4) M), ruthenium red (3 x 10(-5) M), and 18[alpha]-glycyrrhetinic acid (10(-4) M) significantly reduced the responses only in endothelium-intact tissues. These data indicate that in rat mesenteric arteries, EFS leads to vasodilation through both endothelium-dependent and endothelium-independent mechanisms. The major component of the relaxation is endothelium independent and seems to occur via BK(Ca) channels, whereas endothelium-dependent component is likely to be mediated by endothelium-derived hyperpolarizing factor rather than nitric oxide, prostacyclin, or a neural substance. We propose that Ca2+ entry into endothelial cells via nonspecific cation channels in response to EFS induces hyperpolarization by activating endothelial IK(Ca) and SK(Ca) channels, which is spread to the smooth muscle via gap junctions to produce relaxation.

  20. Influence of habitual high dietary fat intake on endothelium-dependent vasodilation

    PubMed Central

    Dow, Caitlin A.; Stauffer, Brian L.; Greiner, Jared J.; DeSouza, Christopher A.

    2016-01-01

    High-fat diets are associated with an increased risk of cardiovascular disease. A potential underlying mechanism for the increased cardiovascular risk is endothelial dysfunction. Nitric oxide (NO)-mediated endothelium-dependent vasodilation is critical in the regulation of vascular tone and overall vascular health. The aim of this study was to determine the influence of dietary fat intake on endothelium-dependent vasodilation. Forty-four middle-aged and older sedentary, healthy adults were studied: 24 consumed a lower fat diet (LFD; 29% ± 1% calories from fat) and 20 consumed a high-fat diet (HFD; 41% ± 1% calories from fat). Four-day diet records were used to assess fat intake, and classifications were based on American Heart Association guidelines (<35% of total calories from fat). Forearm blood flow (FBF) responses to acetylcholine, in the absence and presence of the endothelial NO synthase inhibitor NG-monomethyl-l-arginine (L-NMMA), as well as responses to sodium nitroprusside were determined by plethysmography. The FBF response to acetylcholine was lower (~15%; P < 0.05) in the HFD group (4.5 ± 0.2 to 12.1 ± 0.8 mL/100 mL tissue/min) than in the LFD group (4.6 ± 0.2 to 14.4 ± 0.6 mL/100 mL tissue/min). L-NMMA significantly reduced the FBF response to acetylcholine in the LFD group (~25%) but not in the HFD group. There were no differences between groups in the vasodilator response to sodium nitroprusside. These data indicate that a high-fat diet is associated with endothelium-dependent vasodilator dysfunction due, in part, to diminished NO bioavailability. Impaired NO-mediated endothelium-dependent vasodilation may contribute to the increased cardiovascular risk with high dietary fat intake. PMID:26058441

  1. Influence of habitual high dietary fat intake on endothelium-dependent vasodilation.

    PubMed

    Dow, Caitlin A; Stauffer, Brian L; Greiner, Jared J; DeSouza, Christopher A

    2015-07-01

    High-fat diets are associated with an increased risk of cardiovascular disease. A potential underlying mechanism for the increased cardiovascular risk is endothelial dysfunction. Nitric oxide (NO)-mediated endothelium-dependent vasodilation is critical in the regulation of vascular tone and overall vascular health. The aim of this study was to determine the influence of dietary fat intake on endothelium-dependent vasodilation. Forty-four middle-aged and older sedentary, healthy adults were studied: 24 consumed a lower fat diet (LFD; 29% ± 1% calories from fat) and 20 consumed a high-fat diet (HFD; 41% ± 1% calories from fat). Four-day diet records were used to assess fat intake, and classifications were based on American Heart Association guidelines (<35% of total calories from fat). Forearm blood flow (FBF) responses to 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 plethysmography. The FBF response to acetylcholine was lower (∼15%; P < 0.05) in the HFD group (4.5 ± 0.2 to 12.1 ± 0.8 mL/100 mL tissue/min) than in the LFD group (4.6 ± 0.2 to 14.4 ± 0.6 mL/100 mL tissue/min). L-NMMA significantly reduced the FBF response to acetylcholine in the LFD group (∼25%) but not in the HFD group. There were no differences between groups in the vasodilator response to sodium nitroprusside. These data indicate that a high-fat diet is associated with endothelium-dependent vasodilator dysfunction due, in part, to diminished NO bioavailability. Impaired NO-mediated endothelium-dependent vasodilation may contribute to the increased cardiovascular risk with high dietary fat intake.

  2. Assessment of enhanced endothelium-dependent vasodilation by intermittent fasting in Wistar albino rats.

    PubMed

    Razzak, Rima L Abdul; Abu-Hozaifa, Bodour M; Bamosa, Abdullah O; Ali, Nemah M

    2011-01-01

    Intermittent fasting (IF), a type of feeding regimen where the frequency of eating is reduced enhances cardiovascular stress adaptation and improves cardiovascular risk factors in rats. Data on the effect of IF on the endothelium is not common, so we examined whether IF showed similarity to documented beneficial effects of caloric restriction on endothelium-dependent vasodilatory responses of rat aortic rings. 25 young male Wistar rats had ad libitum (AL) access to food and 25 others were provided with food every other day for 2 months, during which their weight was measured every 2 weeks. Vascular reactivity of abdominal aorta was simultaneously evaluated using dual wire myographs. Weight gain was greater in the AL group (P<0.001) at all weighing intervals. Acetylcholine (ACh; 10(-10)-10(-5)M) produced greater (P<0.05) vasorelaxation in IF rats at the two highest concentrations. IF reduces weight gain in young male rats and improves their aortic endothelium-dependent vasorelaxation.

  3. Stimulation of calcium-sensing receptors induces endothelium-dependent vasorelaxations via nitric oxide production and activation of IKCa channels

    PubMed Central

    Greenberg, Harry Z.E.; Shi, Jian; Jahan, Kazi S.; Martinucci, Matthew C.; Gilbert, Steven J.; Vanessa Ho, W.-S.; Albert, Anthony P.

    2016-01-01

    Stimulation of vascular calcium-sensing receptors (CaSRs) is reported to induce both constrictions and relaxations. However, cellular mechanisms involved in these responses remain unclear. The present study investigates the effect of stimulating CaSRs on vascular contractility and focuses on the role of the endothelium, nitric oxide (NO) and K+ channels in these responses. In wire myography studies, increasing [Ca2 +]o from 1 mM to 6 mM induced concentration-dependent relaxations of methoxamine pre-contracted rabbit mesenteric arteries. [Ca2 +]o-induced relaxations were dependent on a functional endothelium, and were inhibited by the negative allosteric CaSR modulator Calhex-231. [Ca2 +]o-induced relaxations were reduced by inhibitors of endothelial NO synthase, guanylate cyclase, and protein kinase G. CaSR activation also induced NO production in freshly isolated endothelial cells (ECs) in experiments using the fluorescent NO indicator DAF-FM. Pre-treatment with inhibitors of large (BKCa) and intermediate (IKCa) Ca2 +-activated K+ channels (iberiotoxin and charybdotoxin), and Kv7 channels (linopirdine) also reduced [Ca2 +]o-induced vasorelaxations. Increasing [Ca2 +]o also activated IKCa currents in perforated-patch recordings of isolated mesenteric artery ECs. These findings indicate that stimulation of CaSRs induces endothelium-dependent vasorelaxations which are mediated by two separate pathways involving production of NO and activation of IKCa channels. NO stimulates PKG leading to BKCa activation in vascular smooth muscle cells, whereas IKCa activity contributes to endothelium-derived hyperpolarisations. PMID:26772767

  4. Cyclo-oxygenase-2 inhibition and endothelium-dependent vasodilation in younger vs. older healthy adults.

    PubMed

    Eisenach, John H; Gullixson, Leah R; Allen, Alexander R; Kost, Susan L; Nicholson, Wayne T

    2014-10-01

    A major feature of endothelial dysfunction is reduced endothelium-dependent vasodilation, which in ageing may be due to decreased production of endothelial prostacyclin, or nitric oxide (NO), or both. We tested this hypothesis in 12 younger (age 18-38 years, six women) and 12 older healthy adults (age 55-73 years, six post-menopausal women). Endothelium-dependent vasodilation was assessed by the forearm vascular conductance (FVC) response to intra-arterial acetylcholine (ACh) (0.5, 1.0, 2.0, 4.0 μg dl(-1) forearm tissue min(-1) ) before and 90 min after inhibition of the enzyme cyclo-oxygenase-2 (COX-2) with oral celecoxib (400 mg), followed by the addition of endothelial NO synthase inhibition with intra-arterial N(G) -monomethyl-l arginine acetate (L-NMMA). Ageing was associated with a significantly reduced FVC response to ACh (P = 0.009, age-by-dose interaction; highest dose FVC ± SEM in ageing: 11.2 ± 1.4 vs. younger: 17.7 ± 2.4 units, P = 0.02). Celecoxib did not reduce resting FVC or the responses to ACh in any group. L-NMMA significantly reduced resting FVC and the responses to ACh in all groups, and absolute FVC values following L-NMMA were similar between groups. In healthy normotensive younger and older adults, there is minimal contribution of prostacyclin to ACh-mediated vasodilation, yet the NO component of vasodilation is reduced with ageing. In the clinical context, these findings suggest that acute administration of medications that inhibit prostacyclin (i.e. COX-2 inhibitors) evoke modest vascular consequences in healthy persons. Additional studies are necessary to test whether chronic use of COX-2 medications reduces endothelium dependent vasodilation in older persons with or without cardiovascular risk factors. © 2014 The British Pharmacological Society.

  5. Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans.

    PubMed

    Nishioka, Kenji; Hidaka, Takayuki; Nakamura, Shuji; Umemura, Takashi; Jitsuiki, Daisuke; Soga, Junko; Goto, Chikara; Chayama, Kazuaki; Yoshizumi, Masao; Higashi, Yukihito

    2007-09-01

    Pycnogenol, an extract of bark from the French maritime pine, Pinus pinaster Ait., consists of a concentrate of water-soluble polyphenols. Pycnogenol contains the bioflavonoids catechin and taxifolin as well as phenolcarbonic acids. Antioxidants, such as bioflavonoids, enhance endothelial nitric oxide (NO) synthase expression and subsequent NO release from endothelial cells. The purpose of this study was to determine Pycnogenol's effects on endothelium-dependent vasodilation in humans. This was a double-blind, randomized, placebo and active drug study. We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside (SNP), an endothelium-independent vasodilator, in healthy young men before and after 2 weeks of daily oral administration of Pycnogenol (180 mg/day) (n=8) or placebo (n=8). FBF was measured by using strain-gauge plethysmography. Neither the placebo nor Pycnogenol altered forearm or systemic hemodynamics. Pycnogenol, but not placebo, augmented FBF response to ACh, from 13.1 +/- 7.0 to 18.5 +/- 4.0 mL/min per 100 mL tissue (p<0.05). SNP-stimulated vasodilation was similar before and after 2 weeks of treatment in the control and Pycnogenol groups. The administration of N(G)-monomethyl-L-arginine, an NO synthase inhibitor, completely abolished Pycnogenol-induced augmentation of the FBF response to ACh. These findings suggest that Pycnogenol augments endothelium-dependent vasodilation by increasing in NO production. Pycnogenol would be useful for treating various diseases whose pathogeneses involve endothelial dysfunction.

  6. Effects of ageing and exercise training on endothelium-dependent vasodilatation and structure of rat skeletal muscle arterioles

    PubMed Central

    Spier, Scott A; Delp, Michael D; Meininger, Cynthia J; Donato, Anthony J; Ramsey, Michael W; Muller-Delp, Judy M

    2004-01-01

    Ageing reduces endothelium-dependent vasodilatation in humans and animals, and in humans, exercise training reverses the ageing-associated reduction in endothelium-dependent vasodilatation. The purpose of this study was to determine the mechanism(s) by which 10–12 weeks of treadmill exercise enhances endothelium-dependent vasodilatation in muscles of differing fibre composition from young and old rats. Three- and 22-month-old male Fischer 344 rats were assigned to young sedentary, young exercise-trained, old sedentary, or old exercise-trained groups. Arterioles were isolated from the soleus and gastrocnemius muscles; luminal diameter changes were determined in response to the endothelium-dependent vasodilator acetylcholine (ACh, 10−9–10−4 mol l−1) alone and in the presence of the nitric oxide synthase (NOS) inhibitor l-NAME (10−5 mol l−1) or the combination of l-NAME and the cyclooxygenase inhibitor indomethacin (10−5 mol l−1). Training ameliorated the ageing-induced reduction in endothelium-dependent vasodilatation in soleus muscle arterioles. Treatment with l-NAME alone and in combination with indomethacin abolished differences in ACh vasodilatation occurring with ageing and training. Expression of endothelial NOS (eNOS) mRNA in soleus arterioles was unaltered by ageing, whereas eNOS protein was increased with age; training elevated both eNOS mRNA and protein. In gastrocnemius muscle arterioles, ageing did not alter maximal vasodilatation, but ageing and training increased maximal arteriolar diameter. These results demonstrate that ageing-induced reductions and training-induced enhancement of endothelial vasodilatation both occur through the nitric oxide signalling mechanism in highly oxidative skeletal muscle, but ageing and training do not appear to act on the same portion of the signalling cascade. PMID:15004211

  7. Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults.

    PubMed Central

    Clarkson, P; Adams, M R; Powe, A J; Donald, A E; McCredie, R; Robinson, J; McCarthy, S N; Keech, A; Celermajer, D S; Deanfield, J E

    1996-01-01

    In hypercholesterolemic rabbits, oral L-arginine (the substrate for endothelium derived nitric oxide) attenuates endothelial dysfunction and atheroma formation, but the effect in hypercholesterolemic humans is unknown. Using high resolution external ultrasound, we studied arterial physiology in 27 hypercholesterolemic subjects aged 29+/-5 (19-40) years, with known endothelial dysfunction and LDL-cholesterol levels of 238+/-43 mg/dl. Each subject was studied before and after 4 wk of L-arginine (7 grams x 3/day) or placebo powder, with 4 wk washout, in a randomized double-blind crossover study. Brachial artery diameter was measured at rest, during increased flow (causing endothelium-dependent dilation, EDD) and after sublingual glyceryl trinitrate (causing endothelium-independent dilation). After oral L-arginine, plasma L-arginine levels rose from 115+/-103 to 231+/-125 micromol/liter (P<0.001), and EDD improved from 1.7+/-1.3 to 5.6+/-3.0% (P<0.001). In contrast there was no significant change in response to glyceryl trinitrate. After placebo there were no changes in endothelium-dependent or independent vascular responses. Lipid levels were unchanged after L-arginine and placebo. Dietary supplementation with L-arginine significantly improves EDD in hypercholesterolemic young adults, and this may impact favorably on the atherogenic process. PMID:8621785

  8. Relaxation response in femoral angiography.

    PubMed

    Mandle, C L; Domar, A D; Harrington, D P; Leserman, J; Bozadjian, E M; Friedman, R; Benson, H

    1990-03-01

    Immediately before they underwent femoral angiography, 45 patients were given one of three types of audiotapes: a relaxation response tape recorded for this study, a tape of contemporary instrumental music, or a blank tape. All patients were instructed to listen to their audiotape during the entire angiographic procedure. Each audiotape was played through earphones. Radiologists were not told the group assignment or tape contents. The patients given the audiotape with instructions to elicit the relaxation response (n = 15) experienced significantly less anxiety (P less than .05) and pain (P less than .001) during the procedure, were observed by radiology nurses to exhibit significantly less pain (P less than .001) and anxiety (P less than .001), and requested significantly less fentanyl citrate (P less than .01) and diazepam (P less than .01) than patients given either the music (n = 14) or the blank (n = 16) control audiotapes. Elicitation of the relaxation response is a simple, inexpensive, efficacious, and practical method to reduce pain, anxiety, and medication during femoral angiography and may be useful in other invasive procedures.

  9. Endothelium-dependent vasodilatory signalling modulates α1 -adrenergic vasoconstriction in contracting skeletal muscle of humans.

    PubMed

    Hearon, Christopher M; Kirby, Brett S; Luckasen, Gary J; Larson, Dennis G; Dinenno, Frank A

    2016-12-15

    'Functional sympatholysis' describes the ability of contracting skeletal muscle to attenuate sympathetic vasoconstriction, and is critical to ensure proper blood flow and oxygen delivery to metabolically active skeletal muscle. The signalling mechanism responsible for sympatholysis in healthy humans is unknown. Evidence from animal models has identified endothelium-derived hyperpolarization (EDH) as a potential mechanism capable of attenuating sympathetic vasoconstriction. In this study, increasing endothelium-dependent signalling during exercise significantly enhanced the ability of contracting skeletal muscle to attenuate sympathetic vasoconstriction in humans. This is the first study in humans to identify endothelium-dependent regulation of sympathetic vasoconstriction in contracting skeletal muscle, and specifically supports a role for EDH-like vasodilatory signalling. Impaired functional sympatholysis is a common feature of cardiovascular ageing, hypertension and heart failure, and thus identifying fundamental mechanisms responsible for sympatholysis is clinically relevant. Stimulation of α-adrenoceptors elicits vasoconstriction in resting skeletal muscle that is blunted during exercise in an intensity-dependent manner. In humans, the underlying mechanisms remain unclear. We tested the hypothesis that stimulating endothelium-dependent vasodilatory signalling will enhance the ability of contracting skeletal muscle to blunt α1 -adrenergic vasoconstriction. Changes in forearm vascular conductance (FVC; Doppler ultrasound, brachial intra-arterial pressure via catheter) to local intra-arterial infusion of phenylephrine (PE; α1 -adrenoceptor agonist) were calculated during (1) infusion of the endothelium-dependent vasodilators acetylcholine (ACh) and adenosine triphosphate (ATP), the endothelium-independent vasodilator (sodium nitroprusside, SNP), or potassium chloride (KCl) at rest; (2) mild or moderate intensity handgrip exercise; and (3) combined mild exercise

  10. 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

    2017-08-18

    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.

  11. Impairment of Coronary Arteriolar Endothelium-Dependent Dilation after Multi-Walled Carbon Nanotube Inhalation: A Time-Course Study

    PubMed Central

    Stapleton, Phoebe A.; Minarchick, Valerie C.; Cumpston, Amy M.; McKinney, Walter; Chen, Bean T.; Sager, Tina M.; Frazer, David G.; Mercer, Robert R.; Scabilloni, James; Andrew, Michael E.; Castranova, Vincent; Nurkiewicz, Timothy R.

    2012-01-01

    Engineered nanomaterials have been developed for widespread applications due to many highly unique and desirable characteristics. The purpose of this study was to assess pulmonary inflammation and subepicardial arteriolar reactivity in response to multi-walled carbon nanotube (MWCNT) inhalation and evaluate the time course of vascular alterations. Rats were exposed to MWCNT aerosols producing pulmonary deposition. Pulmonary inflammation via bronchoalveolar lavage and MWCNT translocation from the lungs to systemic organs was evident 24 h post-inhalation. Coronary arterioles were evaluated 24–168 h post-exposure to determine microvascular response to changes in transmural pressure, endothelium-dependent and -independent reactivity. Myogenic responsiveness, vascular smooth muscle reactivity to nitric oxide, and α-adrenergic responses all remained intact. However, a severe impact on endothelium-dependent dilation was observed within 24 h after MWCNT inhalation, a condition which improved, but did not fully return to control after 168 h. In conclusion, results indicate that MWCNT inhalation not only leads to pulmonary inflammation and cytotoxicity at low lung burdens, but also a low level of particle translocation to systemic organs. MWCNT inhalation also leads to impairments of endothelium-dependent dilation in the coronary microcirculation within 24 h, a condition which does not fully dissipate within 168 h. The innovations within the field of nanotechnology, while exciting and novel, can only reach their full potential if toxicity is first properly assessed. PMID:23203034

  12. Endothelium-Dependent Vasorelaxant Effects of Dealcoholized Wine Powder of Wild Grape (Vitis coignetiae) in the Rat Thoracic Aorta

    PubMed Central

    Ha, Sang Keun; Park, Ho-Young; Ryu, Mee-Ra; Kim, Yoonsook

    2016-01-01

    The vasorelaxant effects of dealcoholized wild grape (Vitis coignetiae) wine were investigated with isolated rat thoracic aorta. In our present study, we demonstrate that wild grape wine powder (WGWP) induced relaxation of aortic rings preconstricted with norepinephrine in a dose-dependent manner (at concentrations ranging from 0.1 to 1 mg/mL). The vasorelaxant effect of WGWP was dependent on intact endothelia, which was attenuated by incubation with inhibitors of endothelium-derived relaxing factors, such as NG-nitro-L-arginine (nitric oxide synthase inhibitor), methylene blue (guanylate cyclase inhibitor), and indomethacin (cyclooxygenase inhibitor). Moreover, treatment with WGWP and atropine (muscarinic receptor antagonist) or diphenylhydramine (histamine receptor antagonist) significantly inhibited endothelium-dependent vasorelaxation. Our results suggest that WGWP induces relaxation in rat aortic rings in an endothelium-dependent manner. Results further indicate that this effect occurs via nitric oxide-cGMP pathway and prostacyclin-cAMP pathway through a muscarinic receptor and histamine receptor. PMID:27840653

  13. Endothelium-Dependent Contractions of Isolated Arteries to Thymoquinone Require Biased Activity of Soluble Guanylyl Cyclase with Subsequent Cyclic IMP Production.

    PubMed

    Detremmerie, Charlotte M; Chen, Zhengju; Li, Zhuoming; Alkharfy, Khalid M; Leung, Susan W S; Xu, Aimin; Gao, Yuansheng; Vanhoutte, Paul M

    2016-09-01

    Preliminary experiments on isolated rat arteries demonstrated that thymoquinone, a compound widely used for its antioxidant properties and believed to facilitate endothelium-dependent relaxations, as a matter of fact caused endothelium-dependent contractions. The present experiments were designed to determine the mechanisms underlying this unexpected response. Isometric tension was measured in rings (with and without endothelium) of rat mesenteric arteries and aortae and of porcine coronary arteries. Precontracted preparations were exposed to increasing concentrations of thymoquinone, which caused concentration-dependent, sustained further increases in tension (augmentations) that were prevented by endothelium removal, Nω-nitro-L-arginine methyl ester [L-NAME; nitric oxide (NO) synthase inhibitor], and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; soluble guanylyl cyclase [sGC] inhibitor). In L-NAME-treated rings, the NO-donor diethylenetriamine NONOate restored the thymoquinone-induced augmentations; 5-[1-(phenylmethyl)-1H-indazol-3-yl]-2-furanmethanol (sGC activator) and cyclic IMP (cIMP) caused similar restorations. By contrast, in ODQ-treated preparations, the cell-permeable cGMP analog did not restore the augmentation by thymoquinone. The compound augmented the content (measured with ultra-high performance liquid chromatography-tandem mass spectrometry) of cIMP, but not that of cGMP; these increases in cIMP content were prevented by endothelium removal, L-NAME, and ODQ. The augmentation of contractions caused by thymoquinone was prevented in porcine arteries, but not in rat arteries, by 1-(5-isoquinolinylsulfonyl)homopiperazine dihydrochloride and trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide dihydrochloride (Rho-kinase inhibitors); in the latter, but not in the former, it was reduced by 3,5-dichloro-N-[[(1α,5α,6-exo,6α)-3-(3,3-dimethylbutyl)-3-azabicyclo[3.1.0]hex-6-yl]methyl]-benzamide hydrochloride (T-type calcium channel inhibitor

  14. Ambulatory blood pressure monitoring and endothelium-dependent vasodilation in the elderly athletes.

    PubMed

    Galetta, F; Franzoni, F; Plantinga, Y; Ghiadoni, L; Rossi, M; Prattichizzo, F; Carpi, A; Taddei, S; Santoro, G

    2006-09-01

    Regular exercise is a key component of cardiovascular risk prevention strategies, because it is associated with a variety of beneficial metabolic and vascular effects that reduce mortality and the incidence of cardiovascular adverse events. Endothelium plays an important role in the local regulation of vascular tone and structure, mainly by nitric oxide (NO) synthesis and action. Aim of the present study was to evaluate in elderly athletes the effect of regular aerobic exercise on arterial blood pressure (BP) and on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery. The study population included 30 male subjects (mean age 65.6+/-5.6 years), who had practiced endurance running at a competitive level for at least 40 years, and 28 age- and sex-matched subjects (mean age 64.5+/-4.5 years) with sedentary lifestyle and free of cardiovascular disease. Athletes and control subjects underwent standard 12-lead ECG, clinic BP, 24-h ambulatory BP monitoring and endothelium-dependent FMD and endothelium-independent response to glyceryl trinitrate (GTN), 400 microg, in the brachial artery by high-resolution ultrasonography. Systolic clinic and ambulatory 24-h BP were significantly lower in the athletes, than in the controls (P<0.001, respectively). Systolic and diastolic 24-h BP variability, when assessed either by the standard deviation (S.D.), or by the coefficient of variation (CV), were also significantly lower in the athletes (P<0.01). The athletes also had a lower 24-h, day-time and night-time heart rate (HR) (P<0.01), as well as a lower HR variability (P<0.01). As regards circadian BP change, the %Delta was statistically significant greater in athletes (P<0.05). Elderly athletes showed higher FMD than elderly sedentary subjects (P<0.001), whereas no differences were shown in the response to GTN. Our results, suggest that long-term physical activity can counteract the age-related endothelial dysfunction that characterizes sedentary aging, preserving

  15. Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca2+-Activated K+ Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension.

    PubMed

    Seki, Takunori; Goto, Kenichi; Kiyohara, Kanako; Kansui, Yasuo; Murakami, Noboru; Haga, Yoshie; Ohtsubo, Toshio; Matsumura, Kiyoshi; Kitazono, Takanari

    2017-01-01

    Endothelium-dependent hyperpolarization (EDH)-mediated responses are impaired in hypertension, but the underlying mechanisms have not yet been determined. The activation of small- and intermediate-conductance of Ca(2+)-activated K(+) channels (SKCa and IKCa) underpins EDH-mediated responses. It was recently reported that Ca(2+) influx through endothelial transient receptor potential vanilloid type 4 channel (TRPV4) is a prerequisite for the activation of SKCa/IKCa in endothelial cells in specific beds. Here, we attempted to determine whether the impairment of EDH in hypertension is attributable to the dysfunction of TRPV4 and S/IKCa, using isolated superior mesenteric arteries of 20-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto (WKY) rats. In the WKY arteries, EDH-mediated responses were reduced by a combination of SKCa/IKCa blockers (apamin plus TRAM-34; 1-[(2-chlorophenyl)diphenylmethl]-1H-pyrazole) and by the blockade of TRPV4 with the selective antagonist RN-1734 or HC-067047. In the SHRSP arteries, EDH-mediated hyperpolarization and relaxation were significantly impaired when compared with WKY. GSK1016790A, a selective TRPV4 activator, evoked robust hyperpolarization and relaxation in WKY arteries. In contrast, in SHRSP arteries, the GSK1016790A-evoked hyperpolarization was small and relaxation was absent. Hyperpolarization and relaxation to cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, a selective SKCa activator, were marginally decreased in SHRSP arteries compared with WKY arteries. The expression of endothelial TRPV4 and SKCa protein was significantly decreased in the SHRSP mesenteric arteries compared with those of WKY, whereas function and expression of IKCa were preserved in SHRSP arteries. These findings suggest that EDH-mediated responses are impaired in superior mesenteric arteries of SHRSP because of a reduction in both TRPV4 and SKCa input to EDH. © 2016 American Heart

  16. Antihypertensive and endothelium-dependent vasodilator effects of aqueous extract of Cistus ladaniferus.

    PubMed

    Belmokhtar, Mounia; Bouanani, Nour Elhouda; Ziyyat, Abderrahim; Mekhfi, Hassane; Bnouham, Mohamed; Aziz, Mohamed; Matéo, Philippe; Fischmeister, Rodolphe; Legssyer, Abdelkhaleq

    2009-11-06

    Cistus ladaniferus L. (Cistaceae) is a medicinal plant originated from the Mediterranean region which exerts different pharmacological effects. In the present study, our goal was to examine whether the plant possessed antihypertensive properties. Aqueous extract of Cistus leaves (AEC, 500mg/kg/day) reduced systemic blood pressure (SBP) in two animal models of hypertension, the l-NAME and renovascular two kidney-one clip (2K-1C) hypertensive rats. In the former, AEC prevented the increase in SBP when co-administered with l-NAME during four weeks (164+/-3mm Hg in l-NAME vs. 146+/-1mm Hg in l-NAME+AEC, p<0.001). In the latter, AEC reversed the increase in SBP when administered during four weeks after installation of the hypertension (146+/-5mm Hg with AEC vs. 179+/-6mm Hg without, p<0.05). AEC treatment also reversed the endothelial dysfunction observed in both animal models of hypertension. A direct effect on cardiac and vascular tissue was also tested by examining the contractile effects of AEC in rat isolated aortic rings and Langendorff perfused hearts. AEC (10mg/L) had no effect on left ventricular developed pressure and heart rate in isolated perfused heart. However, AEC produced a strong relaxation of pre-contracted rat aortic rings (80+/-2% relaxation, n=25). When the rings were denuded from endothelium or were incubated with 1mM Nomega-nitro-l-arginine (l-NNA), the relaxant effect of AEC was lost. We conclude that C. ladaniferus possesses antihypertensive properties which are mainly due to an endothelium-dependent vasodilatory action.

  17. Differences in responsiveness of intrapulmonary artery and vein to arachidonic acid: mechanism of arterial relaxation involves cyclic guanosine 3':5'-monophosphate and cyclic adenosine 3':5'-monophosphate

    SciTech Connect

    Ignarro, L.J.; Harbison, R.G.; Wood, K.S.; Wolin, M.S.; McNamara, D.B.; Hyman, A.L.; Kadowitz, P.J.

    1985-06-01

    The objective of this study was to examine the relationship between responses of bovine intrapulmonary artery and vein to arachidonic acid and cyclic nucleotide levels in order to better understand the mechanism of relaxation elicited by arachidonic acid and acetylcholine. Arachidonic acid relaxed phenylephrine-precontracted arterial rings and elevated both cyclic GMP and cyclic AMP levels in arteries with intact endothelium. In contrast, endothelium-damaged arterial rings contracted to arachidonic acid without demonstrating significant changes in cyclic nucleotide levels. Indomethacin partially inhibited endothelium-dependent relaxation and abolished cyclic AMP accumulation whereas methylene blue, a guanylate cyclase inhibitor, partially inhibited relaxation and abolished cyclic GMP accumulation in response to arachidonic acid. All vessel responses were blocked by a combination of the two inhibitors. Prostaglandin (PG) I2 relaxed arterial rings and elevated cyclic AMP levels whereas PGE2 and PGF2 alpha caused contraction, suggesting that the indomethacin-sensitive component of arachidonic acid-elicited relaxation is due to PGI2 formation and cyclic AMP accumulation. The methylene blue-sensitive component is attributed to an endothelium-dependent but cyclooxygenase-independent generation of a substance causing cyclic GMP accumulation. Intrapulmonary veins contracted to arachidonic acid with no changes in cyclic nucleotide levels and PGI2 was without effect. Homogenates of intrapulmonary artery and vein formed 6-keto-PGF1 alpha, PGF2 alpha and PGE2 from (/sup 14/C)arachidonic acid, which was inhibited by indomethacin. Thus, bovine intrapulmonary vein may not possess receptors for PGI2.

  18. Activation of TRPV1 by Dietary Capsaicin Improves Endothelium-Dependent Vasorelaxation and Prevents Hypertension

    PubMed Central

    Yang, Dachun; Luo, Zhidan; Ma, Shuangtao; Wong, Wing Tak; Ma, Liqun; Zhong, Jian; He, Hongbo; Zhao, Zhigang; Cao, Tingbing; Yan, Zhencheng; Liu, Daoyan; Arendshorst, William J.; Huang, Yu; Tepel, Martin; Zhu, Zhiming

    2014-01-01

    SUMMARY Some plant-based diets lower the cardiometabolic risks and prevalence of hypertension. New evidence implies a role for the transient receptor potential vanilloid 1 (TRPV1) cation channel in the pathogenesis of cardiometabolic diseases. Little is known about impact of chronic TRPV1 activation on the regulation of vascular function and blood pressure. Here we report that chronic TRPV1 activation by dietary capsaicin increases the phosphorylation of protein kinase A (PKA) and eNOS and thus production of nitric oxide (NO) in endothelial cells, which is calcium dependent. TRPV1 activation by capsaicin enhances endothelium-dependent relaxation in wild-type mice, an effect absent in TRPV1-deficient mice. Long-term stimulation of TRPV1 can activate PKA, which contributes to increased eNOS phosphorylation, improves vasorelaxation, and lowers blood pressure in genetically hypertensive rats. We conclude that TRPV1 activation by dietary capsaicin improves endothelial function. TRPV1-mediated increase in NO production may represent a promising target for therapeutic intervention of hypertension. PMID:20674858

  19. Mechanisms underlying the endothelium-dependent vasodilatory effect of an aqueous extract of Elaeis Guineensis Jacq. (Arecaceae) in porcine coronary artery rings.

    PubMed

    Ndiaye, Mamadou; Anselm, Eric; Séne, Madièye; Diatta, Williams; Dièye, Amadou Moctar; Faye, Babacar; Schini-Kerth, Valérie B

    2009-12-30

    This study was undertaken to investigate the vasodilatory effect of an aqueous extract of Elaeis guineensis Jacq (EGE) in the porcine coronary artery and elicit its possible mechanism(s) of action. Vascular effects of crude extract of dried and powdered leaves of Elaeis guineensis were evaluated on isolated coronary arteries on organ chambers. Determination of eNOS expression and the phosphorylation level of eNOS were determined by Western blot analysis. In the presence of indomethacin, EGE caused pronounced relaxations in endothelium-intact but not in endothelium-denuded coronary artery rings. Relaxations to EGE were significantly reduced by N(ω)-nitro-L-arginine (L-NA, a competitive inhibitor of NO synthase), slightly but not significantly by charybdotoxin plus apamin (two potent inhibitors of EDHF-mediated responses) and abolished by the combination of L-NA and charybdotoxin plus apamin. Relaxations to EGE were abolished by the membrane permeant, SOD mimetic, MnTMPyP, and significantly reduced by wortmannin, an inhibitor of PI3-kinase. Exposure of endothelial cells to EGE increased the phosphorylation level of eNOS at Ser1177 in a time and concentration-dependent manner. MnTMPyP abolished the EGE-induced phosphorylation of eNOS.In conclusion, the obtained data indicate that EGE induces pronounced endothelium-dependent relaxations of the porcine coronary artery, which involve predominantly NO. The stimulatory effect of EGE on eNOS involves the redox-sensitive phosphorylation of eNOS at Ser1177 most likely via the PI3-kinase pathway.

  20. Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

    PubMed Central

    Borgo, M.V.; Claudio, E.R.G.; Silva, F.B.; Romero, W.G.; Gouvea, S.A.; Moysés, M.R.; Santos, R.L.; Almeida, S.A.; Podratz, P.L.; Graceli, J.B.; Abreu, G.R.

    2015-01-01

    Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women. PMID:26577845

  1. Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats.

    PubMed

    Borgo, M V; Claudio, E R G; Silva, F B; Romero, W G; Gouvea, S A; Moysés, M R; Santos, R L; Almeida, S A; Podratz, P L; Graceli, J B; Abreu, G R

    2016-01-01

    Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

  2. Asymmetrical dimethylarginine plasma concentrations are related to basal nitric oxide release but not endothelium-dependent vasodilation of resistance arteries in peritoneal dialysis patients.

    PubMed

    Mittermayer, Friedrich; Schaller, Georg; Pleiner, Johannes; Vychytil, Andreas; Sunder-Plassmann, Gere; Hörl, Walter H; Wolzt, Michael

    2005-06-01

    Vascular dysfunction in chronic renal failure may be linked to reduced nitric oxide (NO) bioactivity and increased circulating concentrations of the endogenous NO synthase inhibitor asymmetrical dimethyl L-arginine (ADMA). The association between ADMA and basal endothelial NO release and endothelium-dependent vasodilation in resistance arteries of chronic renal failure patients is unknown. Forearm blood flow responses to the endothelium-dependent vasodilator acetylcholine, the endothelium-independent vasodilator nitroglycerine, and the endothelium-dependent vasoconstrictor N(G)-monomethyl-L-arginine (L-NMMA) were assessed in 37 peritoneal dialysis patients. L-arginine and ADMA plasma concentrations were measured by HPLC. ADMA (mean +/- SEM: 0.68 +/- 0.02 micromol/L) was associated with basal forearm blood flow (r = -0.33; P < 0.05) and L-NMMA induced vasoconstriction (r = -0.55; P < 0.0005), but not with dilator effects of acetylcholine or nitroglycerine. L-arginine (68 +/- 3 micromol/L) tended to correlate with acetylcholine-induced vasodilation (r = 0.32; P = 0.05) but was not associated with other parameters. ADMA is related to basal but not to acetylcholine-stimulated NO bioactivity in patients on peritoneal dialysis. Impaired endothelium-dependent vasodilation found in chronic renal failure is not explained by elevated circulating NO synthase inhibitors in renal failure.

  3. Intradermal administration of endothelin-1 attenuates endothelium-dependent and -independent cutaneous vasodilation via Rho kinase in young adults.

    PubMed

    Fujii, Naoto; Amano, Tatsuro; Halili, Lyra; Louie, Jeffrey C; Zhang, Sarah Y; McNeely, Brendan D; Kenny, Glen P

    2017-01-01

    We recently showed that intradermal administration of endothelin-1 diminished endothelium-dependent and -independent cutaneous vasodilation. We evaluated the hypothesis that Rho kinase may be a mediator of this response. We also sought to evaluate if endothelin-1 increases sweating. In 12 adults (25 ± 6 yr), we measured cutaneous vascular conductance (CVC) and sweating during 1) endothelium-dependent vasodilation induced via administration of incremental doses of methacholine (0.25, 5, 100, and 2,000 mM each for 25 min) and 2) endothelium-independent vasodilation induced via administration of 50 mM sodium nitroprusside (20-25 min). Responses were evaluated at four skin sites treated with either 1) lactated Ringer solution (Control), 2) 400 nM endothelin-1, 3) 3 mM HA-1077 (Rho kinase inhibitor), or 4) endothelin-1+HA-1077. Pharmacological agents were intradermally administered via microdialysis. Relative to the Control site, endothelin-1 attenuated endothelium-dependent vasodilation (CVC at 2,000 mM methacholine, 80 ± 10 vs. 56 ± 15%max, P < 0.01); however, this response was not detected when the Rho kinase inhibitor was simultaneously administered (CVC at 2,000 mM methacholine for Rho kinase inhibitor vs. endothelin-1 + Rho kinase inhibitor sites: 73 ± 9 vs. 72 ± 11%max, P > 0.05). Endothelium-independent vasodilation was attenuated by endothelin-1 compared with the Control site (CVC, 92 ± 13 vs. 70 ± 14%max, P < 0.01). However, in the presence of Rho kinase inhibition, endothelin-1 did not affect endothelium-independent vasodilation (CVC at Rho kinase inhibitor vs. endothelin-1+Rho kinase inhibitor sites: 81 ± 9 vs. 86 ± 10%max, P > 0.05). There was no between-site difference in sweating throughout (P > 0.05). We show that in young adults, Rho kinase is an important mediator of the endothelin-1-mediated attenuation of endothelium-dependent and -independent cutaneous vasodilation, and that endothelin-1 does not increase sweating. Copyright © 2017 the

  4. Overexpression of endothelial nitric oxide synthase improves endothelium-dependent vasodilation in arteries infused with helper-dependent adenovirus.

    PubMed

    Jiang, Bo; Du, Liang; Flynn, Rowan; Dronadula, Nagadhara; Zhang, Jingwan; Kim, Francis; Dichek, David

    2012-11-01

    Adenoviral vectors (Ad) are useful tools for in vivo gene transfer into endothelial cells. However, endothelium-dependent vasodilation is impaired after Ad infusion, and this impairment is not prevented by use of advanced-generation "helper-dependent" (HD) Ad that lack all viral genes. We hypothesized that endothelium-dependent vasodilation could be improved in Ad-infused arteries by overexpression of endothelial nitric oxide synthase (eNOS). We tested this hypothesis in hyperlipidemic, atherosclerosis-prone rabbits because HDAd will likely be used for treating and preventing atherosclerosis. Moreover, the consequences of eNOS overexpression might differ in normal and atherosclerosis-prone arteries and could include atherogenic effects, as reported in transgenic mice. We cloned rabbit eNOS and constructed an HDAd that expresses it. HDAdeNOS increased NO production by cultured endothelial cells and increased arterial eNOS mRNA in vivo by ∼10-fold. Compared to arteries infused with a control HDAd, HDAdeNOS-infused arteries of hyperlipidemic rabbits had significantly improved endothelium-dependent vasodilation, and similar responses to phenylephrine and nitroprusside. Moreover, infusion of HDAdeNOS had local atheroprotective effects including large, significant decreases in intimal lipid accumulation and arterial tumor necrosis factor (TNF)-α expression (p≤0.04 for both). HDAdeNOS infusion yields a durable (≥2 weeks) increase in arterial eNOS expression, improves vasomotor function, and reduces artery wall inflammation and lipid accumulation. Addition of an eNOS expression cassette improves the performance of HDAd, has no harmful effects, and may reduce atherosclerotic lesion growth.

  5. Overexpression of Endothelial Nitric Oxide Synthase Improves Endothelium-Dependent Vasodilation in Arteries Infused with Helper-Dependent Adenovirus

    PubMed Central

    Jiang, Bo; Du, Liang; Flynn, Rowan; Dronadula, Nagadhara; Zhang, Jingwan; Kim, Francis

    2012-01-01

    Abstract Adenoviral vectors (Ad) are useful tools for in vivo gene transfer into endothelial cells. However, endothelium-dependent vasodilation is impaired after Ad infusion, and this impairment is not prevented by use of advanced-generation “helper-dependent” (HD) Ad that lack all viral genes. We hypothesized that endothelium-dependent vasodilation could be improved in Ad-infused arteries by overexpression of endothelial nitric oxide synthase (eNOS). We tested this hypothesis in hyperlipidemic, atherosclerosis-prone rabbits because HDAd will likely be used for treating and preventing atherosclerosis. Moreover, the consequences of eNOS overexpression might differ in normal and atherosclerosis-prone arteries and could include atherogenic effects, as reported in transgenic mice. We cloned rabbit eNOS and constructed an HDAd that expresses it. HDAdeNOS increased NO production by cultured endothelial cells and increased arterial eNOS mRNA in vivo by ∼10-fold. Compared to arteries infused with a control HDAd, HDAdeNOS-infused arteries of hyperlipidemic rabbits had significantly improved endothelium-dependent vasodilation, and similar responses to phenylephrine and nitroprusside. Moreover, infusion of HDAdeNOS had local atheroprotective effects including large, significant decreases in intimal lipid accumulation and arterial tumor necrosis factor (TNF)-α expression (p≤0.04 for both). HDAdeNOS infusion yields a durable (≥2 weeks) increase in arterial eNOS expression, improves vasomotor function, and reduces artery wall inflammation and lipid accumulation. Addition of an eNOS expression cassette improves the performance of HDAd, has no harmful effects, and may reduce atherosclerotic lesion growth. PMID:22906141

  6. Endothelium-derived Relaxing Factors of Small Resistance Arteries in Hypertension

    PubMed Central

    2014-01-01

    Endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF), play pivotal roles in regulating vascular tone. Reduced EDRFs cause impaired endothelium-dependent vasorelaxation, or endothelial dysfunction. Impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh) is consistently observed in conduit vessels in human patients and experimental animal models of hypertension. Because small resistance arteries are known to produce more than one type of EDRF, the mechanism(s) mediating endothelium-dependent vasorelaxation in small resistance arteries may be different from that observed in conduit vessels under hypertensive conditions, where vasorelaxation is mainly dependent on NO. EDHF has been described as one of the principal mediators of endothelium-dependent vasorelaxation in small resistance arteries in normotensive animals. Furthermore, EDHF appears to become the predominant endothelium-dependent vasorelaxation pathway when the endothelial NO synthase (NOS3)/NO pathway is absent, as in NOS3-knockout mice, whereas some studies have shown that the EDHF pathway is dysfunctional in experimental models of hypertension. This article reviews our current knowledge regarding EDRFs in small arteries under normotensive and hypertensive conditions. PMID:25343007

  7. Antihypertensive treatment and endothelium-dependent venodilation in sleep-disordered breathing.

    PubMed

    Duchna, Hans-Werner; Orth, Maritta; Schultze-Werninghaus, Gerhard; Guilleminault, Christian; Stoohs, Riccardo A

    2006-09-01

    Sleep-disordered breathing (SDB) is associated with nitric oxide-mediated endothelial dysfunction and increased risk and prevalence of cardiovascular disease, namely, arterial hypertension. A substantial number of patients do not comply with nasal continuous positive airway pressure (nCPAP) treatment. These individuals have a persisting increased cardiovascular risk. Antihypertensive drugs have shown to improve nitric oxide-mediated endothelial dysfunction. We therefore designed a study to test the hypothesis that antihypertensive drug treatment in hypertensive patients with SDB can have beneficial effects on nitric oxide-mediated endothelial function in the absence of treatment with nCPAP. Six patients with SDB and treated arterial hypertension, six normotensive patients with SDB, and six healthy controls received sleep studies and an assessment of venodilation using the dorsal hand vein technique. Polygraphic measures using standard overnight sleep studies and dose-response curves to the endothelium-dependent vasodilator bradykinin were obtained. Maximum nitric-oxide-mediated dilation to bradykinin was significantly higher in patients with SDB who had received antihypertensive drug treatment compared to normotensive SDB patients. Nitric oxide-mediated dilation in hypertensive patients with SDB was similar to nitric oxide-mediated dilation in healthy controls. After treatment of normotensive patients with SDB using nCPAP, nitric oxide-mediated dilation in normotensive SDB patients was comparable to nitric oxide-mediated dilation in SDB patients with antihypertensive drug treatment and normal controls. Hypertensive patients with SDB present a normal nitric oxide-mediated endothelial function under antihypertensive treatment.

  8. Associations of resting heart rate with endothelium-dependent vasodilation and shear rate.

    PubMed

    Laosiripisan, Jitanan; Parkhurst, Kristin L; Tanaka, Hirofumi

    2017-01-01

    Heart rate is an independent risk factor for cardiovascular disease and a hemodynamic factor that can modulate blood flow as it affects the frequency of shear stimuli acting on the arterial wall. However, the association between heart rate and endothelium-dependent vasodilation remains highly controversial. We determined the association between heart rate at rest and endothelium-dependent vasodilation in 98 apparently healthy adults (18-63 years). The mild and positive association between heart rate and flow-mediated dilation (FMD) was no longer significant when age and sex or baseline diameter were controlled for. The path analyses revealed that heart rate was not directly related to FMD but the association was indirectly mediated by shear rate, which was confirmed by a bias-corrected bootstrap 95% CIs (0.0157-0.1056). We concluded that even though heart rate and endothelium-dependent vasodilation were associated with shear rate, there was no independent relation between heart rate and FMD.

  9. Integrins mediate mechanical compression–induced endothelium-dependent vasodilation through endothelial nitric oxide pathway

    PubMed Central

    Lu, Xiao

    2015-01-01

    Cardiac and skeletal muscle contraction lead to compression of intramuscular arterioles, which, in turn, leads to their vasodilation (a process that may enhance blood flow during muscle activity). Although endothelium-derived nitric oxide (NO) has been implicated in compression-induced vasodilation, the mechanism whereby arterial compression elicits NO production is unclear. We cannulated isolated swine (n = 39) myocardial (n = 69) and skeletal muscle (n = 60) arteriole segments and exposed them to cyclic transmural pressure generated by either intraluminal or extraluminal pressure pulses to simulate compression in contracting muscle. We found that the vasodilation elicited by internal or external pressure pulses was equivalent; moreover, vasodilation in response to pressure depended on changes in arteriole diameter. Agonist-induced endothelium-dependent and -independent vasodilation was used to verify endothelial and vascular smooth muscle cell viability. Vasodilation in response to cyclic changes in transmural pressure was smaller than that elicited by pharmacological activation of the NO signaling pathway. It was attenuated by inhibition of NO synthase and by mechanical removal of the endothelium. Stemming from previous observations that endothelial integrin is implicated in vasodilation in response to shear stress, we found that function-blocking integrin α5β1 or αvβ3 antibodies attenuated cyclic compression–induced vasodilation and NOx (NO−2 and NO−3) production, as did an RGD peptide that competitively inhibits ligand binding to some integrins. We therefore conclude that integrin plays a role in cyclic compression–induced endothelial NO production and thereby in the vasodilation of small arteries during cyclic transmural pressure loading. PMID:26324675

  10. Integrins mediate mechanical compression-induced endothelium-dependent vasodilation through endothelial nitric oxide pathway.

    PubMed

    Lu, Xiao; Kassab, Ghassan S

    2015-09-01

    Cardiac and skeletal muscle contraction lead to compression of intramuscular arterioles, which, in turn, leads to their vasodilation (a process that may enhance blood flow during muscle activity). Although endothelium-derived nitric oxide (NO) has been implicated in compression-induced vasodilation, the mechanism whereby arterial compression elicits NO production is unclear. We cannulated isolated swine (n = 39) myocardial (n = 69) and skeletal muscle (n = 60) arteriole segments and exposed them to cyclic transmural pressure generated by either intraluminal or extraluminal pressure pulses to simulate compression in contracting muscle. We found that the vasodilation elicited by internal or external pressure pulses was equivalent; moreover, vasodilation in response to pressure depended on changes in arteriole diameter. Agonist-induced endothelium-dependent and -independent vasodilation was used to verify endothelial and vascular smooth muscle cell viability. Vasodilation in response to cyclic changes in transmural pressure was smaller than that elicited by pharmacological activation of the NO signaling pathway. It was attenuated by inhibition of NO synthase and by mechanical removal of the endothelium. Stemming from previous observations that endothelial integrin is implicated in vasodilation in response to shear stress, we found that function-blocking integrin α5β1 or αvβ3 antibodies attenuated cyclic compression-induced vasodilation and NOx (NO(-)2 and NO(-)3) production, as did an RGD peptide that competitively inhibits ligand binding to some integrins. We therefore conclude that integrin plays a role in cyclic compression-induced endothelial NO production and thereby in the vasodilation of small arteries during cyclic transmural pressure loading. © 2015 Lu and Kassab.

  11. Androgen deprivation therapy reversibly increases endothelium-dependent vasodilation in men with prostate cancer.

    PubMed

    Nguyen, Paul L; Jarolim, Petr; Basaria, Shehzad; Zuflacht, Jonah P; Milian, Jessica; Kadivar, Samoneh; Graham, Powell L; Hyatt, Andrew; Kantoff, Philip W; Beckman, Joshua A

    2015-04-20

    Androgen deprivation therapy (ADT) is a standard treatment for patients with aggressive prostate cancer. Although ADT improves survival, it increases the risk of diabetes. Emerging evidence suggests that ADT increases adverse cardiovascular events as early as 3 months after initiation in patients with cardiovascular disease, but the mechanism is unknown. We hypothesized that ADT may impair endothelium-dependent vasodilation due to increases in lipids and insulin resistance and may provide a link for heightened cardiovascular risk in this population. We prospectively evaluated conduit artery endothelium-dependent and -independent vasodilation, lipids, and insulin resistance in 16 consecutively treated men (mean age 66 ± 7 years; 25% with diabetes) with prostate cancer before and after 3 months of ADT. High-resolution B-mode ultrasound was used to assess flow-mediated (endothelium-dependent) and nitroglycerine-mediated (endothelium-independent) brachial artery vasodilation. ADT significantly increased insulin resistance, total cholesterol, HDL, and LDL. Endothelium-dependent vasodilation was greater at 3 months than at baseline (10.8% [interquartile range: 7.7% to 14.6%] versus 8.9% [interquartile range: 4.0% to 12.6%], respectively; P=0.046, allometric P=0.037). Nitroglycerine-mediated vasodilation did not change from baseline (P>0.2). The subset of participants on ADT for 6 months returned for reevaluation at 1 year. In this group, endothelium-dependent vasodilation increased from baseline to 3 months and returned to baseline 6 months after ADT withdrawal (9.4% [interquartile range: 6.9% to 10.9%], 11.6% [interquartile range: 7.9% to 15.2%], and 9.0% [interquartile range: 5.1% to 12.5%], respectively; P=0.05). In contrast to our expectation, ADT improved endothelium-dependent vasodilation and its cessation returned endothelium-dependent vasodilation to baseline. Determining the mechanism of this change requires further investigation. © 2015 The Authors. Published

  12. Long-term Treatment with Hesperidin Improves Endothelium-dependent Vasodilation in Femoral Artery of Spontaneously Hypertensive Rats: The Involvement of NO-synthase and Kv Channels.

    PubMed

    Dobiaš, Lukáš; Petrová, Miriam; Vojtko, Róbert; Kristová, Viera

    2016-10-01

    Hesperidin is the most common flavonoid found in citrus fruits and is expected to exert vasodilation action relevant to its health benefits. The present study aimed to explore the effect of hesperidin on the vascular responses in normotensive and hypertensive rats and the involvement of NO-synthase and Kv channels. The 15-week-old Wistar and spontaneously hypertensive rats (SHR) were randomized to orally receive either hesperidin (50 mg/kg/day) or a corresponding volume of the water for 4 weeks. Vascular responses of isolated femoral arteries were studied with myograph in control conditions and during inhibition of NO-synthase with l-NNA and Kv channels with 4-AP. Hesperidin had no effect on blood pressure. Endothelium-dependent vasodilation in Wistar and SHR was significantly improved by the treatment with hesperidin. The contraction responses after l-NNA were increased in all groups of rats to similar extent, but relaxatory responses were significantly attenuated only in SHR. The inhibition of Kv channels significantly reduced endothelium-dependent vasodilatory responses in only in SHR administered with hesperidin. The results of our experiment indicate that hesperidin might improve the endothelium-dependent vasodilation during hypertension, possibly through the enhancement of Kv channels function. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Serum alkaline phosphatase negatively affects endothelium-dependent vasodilation in naïve hypertensive patients.

    PubMed

    Perticone, Francesco; Perticone, Maria; Maio, Raffaele; Sciacqua, Angela; Andreucci, Michele; Tripepi, Giovanni; Corrao, Salvatore; Mallamaci, Francesca; Sesti, Giorgio; Zoccali, Carmine

    2015-10-01

    Tissue nonspecific alkaline phosphatase, promoting arterial calcification in experimental models, is a powerful predictor of total and cardiovascular mortality in general population and in patients with renal or cardiovascular diseases. For this study, to evaluate a possible correlation between serum alkaline phosphatase levels and endothelial function, assessed by strain gauge plethysmography, we enrolled 500 naïve hypertensives divided into increasing tertiles of alkaline phosphatase. The maximal response to acetylcholine was inversely related to alkaline phosphatase (r=−0.55; P<0.001), and this association was independent (r=−0.61; P<0.001) of demographic and classical risk factors, body mass index, estimated glomerular filtration rate, serum phosphorus and calcium, C-reactive protein, and albuminuria. At multiple logistic regression analysis, the risk of endothelial dysfunction was ≈3-fold higher in patients in the third tertile than that of patients in the first tertile. We also tested the combined role of alkaline phosphatase and serum phosphorus on endothelial function. The steepness of the alkaline phosphatase/vasodilating response to acetylcholine relationship was substantially attenuated (P<0.001) in patients with serum phosphorus above the median value when compared with patients with serum phosphorus below the median (−5.0% versus −10.2% per alkaline phosphatase unit, respectively), and this interaction remained highly significant (P<0.001) after adjustment of all the previously mentioned risk factors. Our data support a strong and significant inverse relationship between alkaline phosphatase and endothelium-dependent vasodilation, which was attenuated by relatively higher serum phosphorus levels.

  14. Novel aspects of endothelium-dependent regulation of vascular tone.

    PubMed

    Villar, I C; Francis, S; Webb, A; Hobbs, A J; Ahluwalia, A

    2006-09-01

    The vascular endothelium plays a crucial role in the regulation of vascular homeostasis and in preventing the initiation and progress of cardiovascular disease by controlling mechanical functions of the underlying vascular smooth muscle. Three vasodilators: nitric oxide (NO), prostacyclin, and endothelium-derived hyperpolarizing factor, produced by the endothelium, underlie this activity. These substances act in a co-ordinated interactive manner to maintain normal endothelial function and operate as support mechanisms when one pathway malfunctions. In this review, we discuss recent advances in our understanding of how gender influences the interaction of these factors resulting in the vascular protective effects seen in pre-menopausal women. We also discuss how endothelial NO synthase (NOS) can act in both a pro- and anti-inflammatory action and therefore is likely to be pivotal in the initiation and time course of an inflammatory response, particularly with respect to inflammatory cardiovascular disorders. Finally, we review recent evidence demonstrating that it is not solely NOS-derived NO that mediates many of the beneficial effects of the endothelium, in particular, nitrite acts as a store of NO released during pathological episodes associated with NOS inactivity (ischemia/hypoxia). Each of these more recent findings has emphasized new pathways involved in endothelial biology, and following further research and understanding of the significance and mechanisms of these systems, it is likely that new and improved treatments for cardiovascular disease will result.

  15. Obesity and risk of vascular disease: importance of endothelium-dependent vasoconstriction.

    PubMed

    Barton, Matthias; Baretella, Oliver; Meyer, Matthias R

    2012-02-01

    Obesity has become a serious global health issue affecting both adults and children. Recent devolopments in world demographics and declining health status of the world's population indicate that the prevalence of obesity will continue to increase in the next decades. As a disease, obesity has deleterious effects on metabolic homeostasis, and affects numerous organ systems including heart, kidney and the vascular system. Thus, obesity is now regarded as an independent risk factor for atherosclerosis-related diseases such as coronary artery disease, myocardial infarction and stroke. In the arterial system, endothelial cells are both the source and target of factors contributing to atherosclerosis. Endothelial vasoactive factors regulate vascular homeostasis under physiological conditions and maintain basal vascular tone. Obesity results in an imbalance between endothelium-derived vasoactive factors favouring vasoconstriction, cell growth and inflammatory activation. Abnormal regulation of these factors due to endothelial cell dysfunction is both a consequence and a cause of vascular disease processes. Finally, because of the similarities of the vascular pathomechanisms activated, obesity can be considered to cause accelerated, 'premature' vascular aging. Here, we will review some of the pathomechanisms involved in obesity-related activation of endothelium-dependent vasoconstriction, the clinical relevance of obesity-associated vascular risk, and therapeutic interventions using 'endothelial therapy' aiming at maintaining or restoring vascular endothelial health. This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  16. Low-intensity voluntary running lowers blood pressure with simultaneous improvement in endothelium-dependent vasodilatation and insulin sensitivity in aged spontaneously hypertensive rats.

    PubMed

    Sun, Meng-Wei; Qian, Feng-Lei; Wang, Jian; Tao, Tao; Guo, Jing; Wang, Lie; Lu, Ai-Yun; Chen, Hong

    2008-03-01

    Our objective is to examine the effects of voluntary running at different intensity levels on blood pressure, endothelium-dependent vessel dysfunction and insulin resistance in aged spontaneously hypertensive rats (SHR) with severe hypertension. Ten-month-old male and female SHR with severe hypertension were assigned to voluntary running at either low intensity (30% of maximal aerobic velocity) or moderate intensity (60% of maximal aerobic velocity) on a motor-driven treadmill for 6 weeks, 20 min per day and 7 days per week. Age-matched Wistar-Kyoto rats and SHR were kept under sedentary conditions as controls. Blood pressure and heart rate were measured by the tail-cuff method. At the end of the exercise training, blood samples were collected for glucose, insulin and lipids assay, and aortae were isolated to examine their function in vitro. Low-intensity but not moderate-intensity running significantly lowered blood pressure in both male and female SHR (p<0.01). There was significant impairment in acetylcholine-induced vasorelaxation in SHR (p<0.01), which was improved by low-intensity training (p<0.05). Nitric oxide synthase blockade abrogated the improvement in endothelium-dependent relaxation. Hypertensive rats had elevated blood glucose and insulin levels with lowered insulin sensitivity that was ameliorated by low-intensity running. A significant increase in blood high-density lipoprotein (HDL)-cholesterol and a significant decrease in triglycerides were found in exercised SHR. In conclusion, low-intensity voluntary exercise lowers hypertension in aged SHR with severe hypertension. Exercise-induced simultaneous improvement in endothelium-dependent vessel relaxation and insulin sensitivity may act concomitantly in attenuating cardiovascular risk factors in aged hypertensive rats with significantly high blood pressure.

  17. Captopril, but not nifedipine, improves endothelium-dependent vasodilation in hypertensive patients.

    PubMed

    Millgård, J; Hägg, A; Sarabi, M; Lind, L

    1998-08-01

    The present study aimed to investigate the influence of the angiotensin-converting enzyme (ACE)-inhibitor captopril and the Ca-antagonist nifedipine on endothelium-dependent vasodilation (EDV) in the forearm of hypertensive patients. Twenty-three middle-aged untreated hypertensive patients underwent evaluation of EDV and endothelium-independent vasodilation (EIDV) in the forearm, by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium-nitroprusside (SNP, evaluating EIDV), before and 1 h after intake of either captopril (25 mg) or nifedipine (10 mg) in a randomised, double-blind fashion. A matched normotensive control group was investigated at baseline conditions only. Five of the hypertensives were also evaluated after 3 months of treatment with captopril 25 mg twice daily in an open pilot study. First, the vasodilation induced by methacholine (MCh), but not SNP, was significantly attenuated in the hypertensive patients compared to the normotensive controls (P < 0.001 at MCh 4 microg/min). Second, although the two drugs induced a similar decline in blood pressure (BP) 1 h after administration (-11 to 10 mm Hg/-8 to 7 mm Hg), captopril significantly potentiated the vasodilator response to MCh (+32+/-13%, MCh 4 micr og/min, P < 0.01) but not SNP, while nifedipine did not significantly alter the response to either MCh or SNP. The improvement in vasodilator response to MCh induced by captopril was closely related to the reduction in BP (r = 0.72, P < 0.01). Third, in the pilot study, 3 months of captopril treatment induced a significant potentiation of the vasodilator response to MCh (+34+/-17%, MCh 4 microg/min, P < 0.05) in parallel with a significant BP reduction (-22+/-24/13+/-13 mm Hg, P < 0.05), while the response to SNP was unchanged. In conclusion, the present study confirmed that essential hypertension is associated with a defect in EDV. Furthermore, an improvement in EDV was seen in hypertensive patients shortly after

  18. Contribution of prostanoids to endothelium-dependent vasodilatation in the digital circulation of women with primary Raynaud's disease.

    PubMed

    Easter, Melanie J; Marshall, Janice M

    2005-07-01

    In 15 women with PR (primary Raynaud's) disease and in 15 matched control women, ACh (acetylcholine) was delivered by iontophoresis to the dorsum of the finger (seven 20 s pulses of 0.1 mA, followed by one 20 s pulse of 0.2 mA, applied at 60 s intervals). Cutaneous RCF (red cell flux) was recorded from the same site by the laser Doppler technique. ACh evoked progressive increases in RCF that were comparable in pre- and post-menopausal women with PR [maxima of 294+/-113 and 259+/-59 pu (perfusion units) respectively, n = 7 and 8 respectively], and in pre-menopausal controls (225+/-92 pu, n = 7), but smaller in post-menopausal controls (140+/-63 pu, n = 8; P < 0.05). Aspirin (600 mg, orally), a COX (cyclo-oxygenase) inhibitor, potentiated the ACh-evoked dilator responses in pre- and post-menopausal women with PR (343+/-129 and 311+/-48 pu respectively) and post-menopausal controls (277+/-124 pu; P < 0.05), but had no effect in pre-menopausal controls (225+/-92 pu). These results suggest that vasoconstrictor COX products limit ACh-evoked endothelium-dependent cutaneous dilatation in the digits in pre- and post-menopausal women with PR and in post-menopausal, but not pre-menopausal, control women. We propose that PR disease is associated with abnormality in the ability of oestrogen to modulate the synthesis of endothelium-dependent vasodilator and/or vasoconstrictor COX products.

  19. Calycosin and Formononetin Induce Endothelium-Dependent Vasodilation by the Activation of Large-Conductance Ca2+-Activated K+ Channels (BKCa)

    PubMed Central

    Tseng, Hisa Hui Ling; Vong, Chi Teng; Leung, George Pak-Heng; Seto, Sai Wang; Lee, Simon Ming-Yuen

    2016-01-01

    Calycosin and formononetin are two structurally similar isoflavonoids that have been shown to induce vasodilation in aorta and conduit arteries, but study of their actions on endothelial functions is lacking. Here, we demonstrated that both isoflavonoids relaxed rat mesenteric resistance arteries in a concentration-dependent manner, which was reduced by endothelial disruption and nitric oxide synthase (NOS) inhibition, indicating the involvement of both endothelium and vascular smooth muscle. In addition, the endothelium-dependent vasodilation, but not the endothelium-independent vasodilation, was blocked by BKCa inhibitor iberiotoxin (IbTX). Using human umbilical vein endothelial cells (HUVECs) as a model, we showed calycosin and formononetin induced dose-dependent outwardly rectifying K+ currents using whole cell patch clamp. These currents were blocked by tetraethylammonium chloride (TEACl), charybdotoxin (ChTX), or IbTX, but not apamin. We further demonstrated that both isoflavonoids significantly increased nitric oxide (NO) production and upregulated the activities and expressions of endothelial NOS (eNOS) and neuronal NOS (nNOS). These results suggested that calycosin and formononetin act as endothelial BKCa activators for mediating endothelium-dependent vasodilation through enhancing endothelium hyperpolarization and NO production. Since activation of BKCa plays a role in improving behavioral and cognitive disorders, we suggested that these two isoflavonoids could provide beneficial effects to cognitive disorders through vascular regulation. PMID:27994632

  20. Coronary β2-adrenoreceptors mediate endothelium-dependent vasoreactivity in humans: novel insights from an in vivo intravascular ultrasound study.

    PubMed

    Puri, Rishi; Liew, Gary Y H; Nicholls, Stephen J; Nelson, Adam J; Leong, Darryl P; Carbone, Angelo; Copus, Barbara; Wong, Dennis T L; Beltrame, John F; Worthley, Stephen G; Worthley, Matthew I

    2012-02-01

    The interaction between coronary β(2)-adrenoreceptors and segmental plaque burden is complex and poorly understood in humans. We aimed to validate intracoronary (IC) salbutamol as a novel endothelium-dependent vasodilator utilizing intravascular ultrasound (IVUS), and thus assess relationships between coronary β(2)-adrenoreceptors, regional plaque burden and segmental endothelial function. In 29 patients with near-normal coronary angiograms, IVUS-upon-Doppler Flowire imaging protocols were performed. Protocol 1: incremental IC salbutamol (0.15, 0.30, 0.60 μg/min) infusions (15 patients, 103 segments); protocol 2: salbutamol (0.30 μg/min) infusion before and after IC administration of N(G)-monomethyl-L-arginine (L-NMMA) (10 patients, 82 segments). Vehicle infusions (IC dextrose) were performed in 4 patients (21 segments). Macrovascular response [% change segmental lumen volume (ΔSLV)] and plaque burden [per cent atheroma volume (PAV)] were studied in 5-mm coronary segments. Microvascular response [per cent change in coronary blood flow (ΔCBF)] was calculated following each infusion. Intracoronary salbutamol demonstrated significant dose-response ΔSLV and ΔCBF from baseline, respectively (0.15 μg/min: 3.5 ± 1.3%, 28 ± 14%, P = 0.04, P = NS; 0.30 μg/min: 5.5 ± 1.4%, 54 ± 17%, P = 0.001, P < 0.0001; 0.60 μg/min: 4.8 ± 1.6%, 66 ± 15%, P = 0.02, P < 0.0001), with ΔSLV responses further exemplified in low vs. high plaque burden groups. Salbutamol vasomotor responses were suppressed by l-NMMA, supporting nitric oxide-dependent mechanisms. Vehicle infusions resulted in no significant ΔSLV or ΔCBF. Multivariate analysis including conventional cardiovascular risk factors, PAV, segmental remodelling and plaque eccentricity indices identified PAV as the only significant predictor of a ΔSLV to IC salbutamol (coefficient -0.18, 95% CI -0.32 to -0.044, P = 0.015). Conclusions Intracoronary salbutamol is a novel endothelium-dependent epicardial and

  1. The Effects of Progressive Relaxation and Music on Attention, Relaxation and Stress Responses: An Investigation of the Cognitive-Behavioral Model of Relaxation

    DTIC Science & Technology

    1999-01-28

    295’-6772 APPROVAL SHEET Title ofDissertation: "The Effects ofProgressive Relaxation and Music on Attention, Relaxation~ and Stress Responses: An...and Music on Attention, Relaxation, and Stress Responses: An Investigation of the Cognitive-Behavioral Model of Relaxation.n beyond brief excerpts is...Health Sciences ii ABSTRACT Title: The Effects of Progressive Relaxation and Music on Attention, Relaxation, and Stress Responses: An Investigation of

  2. Vascular Endothelium-Dependent and Independent Actions of Oleanolic Acid and Its Synthetic Oleanane Derivatives as Possible Mechanisms for Hypotensive Effects

    PubMed Central

    Madlala, Hlengiwe P.; Metzinger, Thomas; van Heerden, Fanie R.; Mubagwa, Kanigula; Dessy, Chantal

    2016-01-01

    Purpose Plant-derived oleanolic acid (OA) and its related synthetic derivatives (Br-OA and Me-OA) possess antihypertensive effects in experimental animals. The present study investigated possible underlying mechanisms in rat isolated single ventricular myocytes and in vascular smooth muscles superfused at 37°C. Methods Cell shortening was assessed at 1 Hz using a video-based edge-detection system and the L-type Ca2+ current (ICaL) was measured using the whole-cell patch-clamp technique in single ventricular myocytes. Isometric tension was measured using force transducer in isolated aortic rings and in mesenteric arteries. Vascular effects were measured in endothelium-intact and denuded vessels in the presence of various enzyme or channel inhibitors. Results OA and its derivatives increased cell shortening in cardiomyocytes isolated from normotensive rats but had no effect in those isolated from hypertensive animals. These triterpenes also caused relaxation in aortic rings and in mesenteric arteries pre-contracted with either phenylephrine or KCl-enriched solution. The relaxation was only partially inhibited by endothelium denudation, and also partly inhibited by the cyclooxygenase (COX) inhibitor indomethacin, with no additional inhibitory effect of the NO synthase inhibitor, N-ω-Nitro-L-arginine. A combination of both ATP-dependent channel inhibition by glibenclaminde and voltage-dependent K+ channel inhibition by 4-aminopyridine was necessary to fully inhibit the relaxation. Conclusion These data indicate that the effects of OA and its derivatives are mediated via both endothelium-dependent and independent mechanisms suggesting the involvement of COX in the endothelium-dependent effects and of vascular muscle K+ channels in the endothelium-independent effects. Finally, our results support the view that the antihypertensive action of OA and its derivatives is due to a decrease of vascular resistance with no negative inotropic effect on the heart. PMID:26799746

  3. In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury

    PubMed Central

    Rannou, Emilie; François, Agnès; Toullec, Aurore; Guipaud, Olivier; Buard, Valérie; Tarlet, Georges; Mintet, Elodie; Jaillet, Cyprien; Iruela-Arispe, Maria Luisa; Benderitter, Marc; Sabourin, Jean-Christophe; Milliat, Fabien

    2015-01-01

    The pathophysiological mechanism involved in side effects of radiation therapy, and especially the role of the endothelium remains unclear. Previous results showed that plasminogen activator inhibitor-type 1 (PAI-1) contributes to radiation-induced intestinal injury and suggested that this role could be driven by an endothelium-dependent mechanism. We investigated whether endothelial-specific PAI-1 deletion could affect radiation-induced intestinal injury. We created a mouse model with a specific deletion of PAI-1 in the endothelium (PAI-1KOendo) by a Cre-LoxP system. In a model of radiation enteropathy, survival and intestinal radiation injury were followed as well as intestinal gene transcriptional profile and inflammatory cells intestinal infiltration. Irradiated PAI-1KOendo mice exhibited increased survival, reduced acute enteritis severity and attenuated late fibrosis compared with irradiated PAI-1flx/flx mice. Double E-cadherin/TUNEL labeling confirmed a reduced epithelial cell apoptosis in irradiated PAI-1KOendo. High-throughput gene expression combined with bioinformatic analyses revealed a putative involvement of macrophages. We observed a decrease in CD68+cells in irradiated intestinal tissues from PAI-1KOendo mice as well as modifications associated with M1/M2 polarization. This work shows that PAI-1 plays a role in radiation-induced intestinal injury by an endothelium-dependent mechanism and demonstrates in vivo that the endothelium is directly involved in the progression of radiation-induced enteritis. PMID:26510580

  4. Measurement of endothelium-dependent vasodilation in mice--brief report.

    PubMed

    Schuler, Dominik; Sansone, Roberto; Freudenberger, Till; Rodriguez-Mateos, Ana; Weber, Gesine; Momma, Tony Y; Goy, Christine; Altschmied, Joachim; Haendeler, Judith; Fischer, Jens W; Kelm, Malte; Heiss, Christian

    2014-12-01

    Endothelium-dependent, flow-mediated vasodilation after an increase in shear stress at the endothelial lining of conduit arteries during reactive hyperemia after ischemia is a fundamental principle of vascular physiology adapting blood flow to demand of supplied tissue. Flow-mediated vasodilation measurements have been performed in human studies and are of diagnostic and prognostic importance, but have been impossible because of technical limitations in transgenic mice to date, although these represent the most frequently used animal model in cardiovascular research. Using high-frequency ultrasound, we visualized, quantified, and characterized for the first time endothelium-dependent dilation of the femoral artery after temporal ischemia of the lower part of the hindlimb and demonstrated that the signaling was almost exclusively dependent on stimulation of endothelial nitric oxide synthase, similar to acetylcholine, completely abolished after pharmacological or genetic inhibition of endothelial nitric oxide synthase and endothelial denudation, substantially impaired in mice of increasing age and cholesterol-fed ApoE knock outs and increased by the dietary polyphenol (-)-epicatechin. Intra- and interindividual variability were similar to the human methodology. The physiology of flow-mediated vasodilation in mice resembles that in humans underscoring the significance of this novel technology to noninvasively, serially, and reliably quantify flow-mediated vasodilation in transgenic mice. © 2014 American Heart Association, Inc.

  5. HDL particles from type 1 diabetic patients are unable to reverse the inhibitory effect of oxidised LDL on endothelium-dependent vasorelaxation.

    PubMed

    Perségol, L; Foissac, M; Lagrost, L; Athias, A; Gambert, P; Vergès, B; Duvillard, L

    2007-11-01

    In healthy individuals, HDL can counteract the inhibition of vasorelaxation induced by oxidised LDL. Several abnormalities such as increased size, glycation and decreased paraoxonase activity have been reported for HDL from type 1 diabetic patients. Thus, we hypothesised that the ability of HDL to protect vessels against impairments of vasorelaxation would be decreased in these patients. We compared the ability of HDL from 18 type 1 diabetic patients and 12 control participants to counteract the inhibition of endothelium-dependent relaxation induced by oxidised LDL on rabbit aorta rings. Serum triacylglycerol and total cholesterol, LDL- and HDL-cholesterol were similar in type 1 diabetic and control participants. Fasting glycaemia and the HDL-fructosamine level were higher in diabetic patients than in controls (9.06 +/- 3.55 vs 5.27 +/- 0.23 mmol/l, p < 0.005; and 10.2 +/- 3.2 vs 7.7 +/- 2.5 micromol/g protein, p < 0.05, respectively). HDL composition, size and paraoxonase activity were similar in both groups. HDL from controls reduced the inhibitory effect of oxidised LDL on maximal relaxation (E (max); 79.3 +/- 11.8 vs 66.4 +/- 11.7%, p < 0.05), whereas HDL from type 1 diabetic patients had no effect (E (max) = 70.6 +/- 17.4 vs 63.9 +/- 17.2%, NS). In type 1 diabetic patients, E (max) was not correlated with glycaemia or the HDL-fructosamine level. HDL particles from type 1 diabetic patients do not protect against inhibition of endothelium-dependent vasorelaxation induced by oxidised LDL, in contrast to HDL particles from healthy individuals. This defect cannot be explained by abnormalities in HDL composition, size or paraoxonase activity, and may contribute to the early development of atherosclerotic lesions in type 1 diabetic patients.

  6. Endothelium-Dependent and -Independent Vasodilator Effects of Dimethyl Sulfoxide in Rat Aorta.

    PubMed

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

    2016-01-01

    This study examined the mechanism of vasorelaxation induced by dimethyl sulfoxide (DMSO) in endothelium-intact and -denuded rat aorta. DMSO (0.1-3%) inhibited phenylephrine (PE, 1 μmol/l)-induced contraction in a dose-dependent manner. However, this relaxation was lower in the absence of the endothelium. Increase in DMSO-induced relaxation in the presence of the endothelium was attenuated by preincubation in L-NG-nitroarginine methyl ester (L-NAME, 100 μmol/l) and by the removal of the endothelium. In the aorta with endothelium, DMSO (3%) and CCh (3 μmol/l) increased cGMP contents, significantly and L-NAME (100 μmol/l) inhibited the DMSO-induced increases of cGMP. In fura 2-loaded endothelium-denuded aorta, cumulative application of DMSO (1-3%) inhibited PE-induced muscle tension; however, this application did not affect the [Ca2+]i level. In PE-precontracted endothelium-denuded aorta, relaxation responses to fasudil were significantly less in the presence of DMSO compared to the control. These results suggest that DMSO causes relaxation by increasing the cGMP content in correlation with the release of NO from endothelial cells and by decreasing the Ca2+ sensitivity of contractile elements partly via inhibiting Rho-kinase in rat aorta.

  7. Hindlimb unweighting decreases endothelium-dependent dilation and eNOS expression in soleus not gastrocnemius

    NASA Technical Reports Server (NTRS)

    Woodman, C. R.; Schrage, W. G.; Rush, J. W.; Ray, C. A.; Price, E. M.; Hasser, E. M.; Laughlin, M. H.

    2001-01-01

    We tested the hypothesis that hindlimb unweighting (HLU) decreases endothelium-dependent vasodilation and expression of endothelial nitric oxide synthase (eNOS) and superoxide dismutase-1 (SOD-1) in arteries of skeletal muscle with reduced blood flow during HLU. Sprague-Dawley rats (300-350 g) were exposed to HLU (n = 15) or control (n = 15) conditions for 14 days. ACh-induced dilation was assessed in muscle with reduced [soleus (Sol)] or unchanged [gastrocnemius (Gast)] blood flow during HLU. eNOS and SOD-1 expression were measured in feed arteries (FA) and in first-order (1A), second-order (2A), and third-order (3A) arterioles. Dilation to infusion of ACh in vivo was blunted in Sol but not Gast. In arteries of Sol muscle, HLU decreased eNOS mRNA and protein content. eNOS mRNA content was significantly less in Sol FA (35%), 1A arterioles (25%) and 2A arterioles (18%). eNOS protein content was less in Sol FA (64%) and 1A arterioles (65%) from HLU rats. In arteries of Gast, HLU did not decrease eNOS mRNA or protein. SOD-1 mRNA expression was less in Sol 2A arterioles (31%) and 3A arterioles (29%) of HLU rats. SOD-1 protein content was less in Sol FA (67%) but not arterioles. SOD-1 mRNA and protein content were not decreased in arteries from Gast. These data indicate that HLU decreases endothelium-dependent vasodilation, eNOS expression, and SOD-1 expression primarily in arteries of Sol muscle where blood flow is reduced during HLU.

  8. Effects of sapropterin on endothelium-dependent vasodilation in patients with CADASIL: a randomized controlled trial.

    PubMed

    De Maria, Renata; Campolo, Jonica; Frontali, Marina; Taroni, Franco; Federico, Antonio; Inzitari, Domenico; Tavani, Alessandra; Romano, Silvia; Puca, Emanuele; Orzi, Francesco; Francia, Ada; Mariotti, Caterina; Tomasello, Chiara; Dotti, Maria Teresa; Stromillo, Maria Laura; Pantoni, Leonardo; Pescini, Francesca; Valenti, Raffaella; Pelucchi, Claudio; Parolini, Marina; Parodi, Oberdan

    2014-10-01

    Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a rare autosomal dominant disorder caused by NOTCH3 mutations, is characterized by vascular smooth muscle and endothelial cells abnormalities, altered vasoreactivity, and recurrent lacunar infarcts. Vasomotor function may represent a key factor for disease progression. Tetrahydrobiopterin, essential cofactor for nitric oxide synthesis in endothelial cells, ameliorates endothelial function. We assessed whether supplementation with sapropterin, a synthetic tetrahydrobiopterin analog, improves endothelium-dependent vasodilation in CADASIL patients. In a 24-month, multicenter randomized, double-blind, placebo-controlled trial, CADASIL patients aged 30 to 65 years were randomly assigned to receive placebo or sapropterin 200 to 400 mg BID. The primary end point was change in the reactive hyperemia index by peripheral arterial tonometry at 24 months. We also assessed the safety and tolerability of sapropterin. Analysis was done by intention-to-treat. The intention-to-treat population included 61 patients. We found no significant difference between sapropterin (n=32) and placebo (n=29) in the primary end point (mean difference in reactive hyperemia index by peripheral arterial tonometry changes 0.19 [95% confidence interval, -0.18, 0.56]). Reactive hyperemia index by peripheral arterial tonometry increased after 24 months in 37% of patients on sapropterin and in 28% on placebo; however, after adjustment for age, sex, and clinical characteristics, improvement was not associated with treatment arm. The proportion of patients with adverse events was similar on sapropterin and on placebo (50% versus 48.3%); serious adverse events occurred in 6.3% versus 13.8%, respectively. Sapropterin was safe and well-tolerated at the average dose of 5 mg/kg/day, but did not affect endothelium-dependent vasodilation in CADASIL patients. https://www.clinicaltrialsregister.eu. Unique

  9. High Dietary Sodium Intake Impairs Endothelium-Dependent Dilation in Healthy Salt-Resistant Humans

    PubMed Central

    DuPont, Jennifer J.; Greaney, Jody L.; Wenner, Megan M.; Lennon-Edwards, Shannon L.; Sanders, Paul W.; Farquhar, William B.; Edwards, David G.

    2014-01-01

    Excess dietary sodium has been linked to the development of hypertension and other cardiovascular diseases. In humans, the effects of sodium consumption on endothelial function have not been separated from the effects on blood pressure. The present study was designed to determine if dietary sodium intake affected endothelium-dependent dilation (EDD) independently of changes in blood pressure. Fourteen healthy salt resistant adults were studied (9M, 5F; age 33 ± 2.4 years) in a controlled feeding study. After a baseline run-in diet, participants were randomized to a 7 day high sodium (HS) (300-350 mmol/day) and 7 day low sodium (LS) (20 mmol/day) diet. Salt resistance, defined as a ≤ 5 mm Hg change in a 24-hour mean arterial pressure, was individually assessed while on the low sodium and high sodium diets and confirmed in the subjects undergoing study (LS: 85±1 mm Hg; HS: 85±2 mmHg). EDD was determined in each subject via brachial artery flow-mediated dilation on the last day of each diet. Sodium excretion increased during the high sodium diet (p < 0.01). EDD was reduced on the high sodium diet (Low: 10.3±0.9%, High: 7.3±0.7%, p < 0.05). The HS diet significantly suppressed plasma renin activity (PRA), plasma angiotensin II, and aldosterone (p < 0.05). These data demonstrate that excess salt intake in humans impairs endothelium-dependent dilation independently of changes in blood pressure. PMID:23263240

  10. Hindlimb unweighting decreases endothelium-dependent dilation and eNOS expression in soleus not gastrocnemius

    NASA Technical Reports Server (NTRS)

    Woodman, C. R.; Schrage, W. G.; Rush, J. W.; Ray, C. A.; Price, E. M.; Hasser, E. M.; Laughlin, M. H.

    2001-01-01

    We tested the hypothesis that hindlimb unweighting (HLU) decreases endothelium-dependent vasodilation and expression of endothelial nitric oxide synthase (eNOS) and superoxide dismutase-1 (SOD-1) in arteries of skeletal muscle with reduced blood flow during HLU. Sprague-Dawley rats (300-350 g) were exposed to HLU (n = 15) or control (n = 15) conditions for 14 days. ACh-induced dilation was assessed in muscle with reduced [soleus (Sol)] or unchanged [gastrocnemius (Gast)] blood flow during HLU. eNOS and SOD-1 expression were measured in feed arteries (FA) and in first-order (1A), second-order (2A), and third-order (3A) arterioles. Dilation to infusion of ACh in vivo was blunted in Sol but not Gast. In arteries of Sol muscle, HLU decreased eNOS mRNA and protein content. eNOS mRNA content was significantly less in Sol FA (35%), 1A arterioles (25%) and 2A arterioles (18%). eNOS protein content was less in Sol FA (64%) and 1A arterioles (65%) from HLU rats. In arteries of Gast, HLU did not decrease eNOS mRNA or protein. SOD-1 mRNA expression was less in Sol 2A arterioles (31%) and 3A arterioles (29%) of HLU rats. SOD-1 protein content was less in Sol FA (67%) but not arterioles. SOD-1 mRNA and protein content were not decreased in arteries from Gast. These data indicate that HLU decreases endothelium-dependent vasodilation, eNOS expression, and SOD-1 expression primarily in arteries of Sol muscle where blood flow is reduced during HLU.

  11. 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.

  12. Retrospectively gated MRI for in vivo assessment of endothelium-dependent vasodilatation and endothelial permeability in murine models of endothelial dysfunction.

    PubMed

    Bar, Anna; Skórka, Tomasz; Jasiński, Krzysztof; Sternak, Magdalena; Bartel, Żaneta; Tyrankiewicz, Urszula; Chlopicki, Stefan

    2016-08-01

    Endothelial dysfunction is linked to impaired endothelial-dependent vasodilatation and permeability changes. Here, we quantify both of these phenomena associated with endothelial dysfunction by MRI in vivo in mice. Endothelial function was evaluated in the brachiocephalic artery (BCA) and left carotid artery (LCA) in ApoE/LDLR(-/-) and high-fat diet (HFD)-fed mice as compared with control mice (C57BL/6J). The 3D IntraGate® FLASH sequence was used for evaluation of changes in vessels' cross-sectional area (CSA) and volume following acetylcholine (Ach) administration. Evaluation of endothelial permeability after administration of contrast agent (Galbumin, BioPAL) was based on the variable flip angle method for the assessment of parameters based on the relaxation time (T1 ) value. In order to confirm the involvement of nitric oxide (NO) in response to Ach, L-NAME-treated mice were also analyzed. To confirm that endothelial permeability changes accompany the impairment of Ach-dependent vasodilatation, permeability changes were analyzed in isolated, perfused carotid artery. In C57BL/6J mice, Ach-induced vasodilatation led to an approximately 25% increase in CSA in both vessels, which was temporarily dissociated from the effect of Ach on heart rate. In ApoE/LDLR(-/-) or HFD-fed mice Ach induced a paradoxical vasoconstriction that amounted to approximately 30% and 50% decreases in CSA of BCA and LCA respectively. In ApoE/LDLR(-/-) and HFD-fed mice endothelial permeability in BCA was also increased (fall in T1 by about 25%). In L-NAME-treated mice Ach-induced vasodilatation in BCA was lost. In isolated, perfused artery from ApoE/LDLR(-/-) mice endothelial permeability was increased. MRI-based assessment of endothelium-dependent vasodilatation induced by Ach and endothelial permeability using a retrospectively self-gated 3D gradient-echo sequence (IntraGate® FLASH) enables the reliable detection of systemic endothelial dysfunction in mice and provides an important tool

  13. Involvement of thromboxane A2 in the endothelium-dependent contractions induced by myricetin in rat isolated aorta

    PubMed Central

    Jiménez, Rosario; Andriambeloson, Emile; Duarte, Juan; Andriantsitohaina, Ramaroson; Jiménez, José; Pérez-Vizcaino, Francisco; Zarzuelo, Antonio; Tamargo, Juan

    1999-01-01

    The present study was undertaken to analyse the mechanism of the contractile response induced by the bioflavonoid myricetin in isolated rat aortic rings.Myricetin induced endothelium-dependent contractile responses (maximal value=21±2% of the response induced by 80 mM KCl and pD2=5.12±0.03). This effect developed slowly, reached a peak within 6 min and then declined progressively.Myricetin-induced contractions were almost abolished by the phospholipase A2 (PLA2) inhibitor, quinacrine (10 μM), the cyclo-oxygenase inhibitor, indomethacin (10 μM), the thromboxane synthase inhibitor, dazoxiben (100 μM), the putative thromboxane A2 (TXA2)/prostaglandin endoperoxide receptor antagonist, ifetroban (3 μM). These contractions were abolished in Ca2+-free medium but were not affected by the Ca2+ channel blocker verapamil (10 μM).In cultured bovine endothelial cells (BAEC), myricetin (50 μM) produced an increase in cytosolic free calcium ([Ca2+]i) which peaked within 1 min and remained sustained for 6 min, as determined by the fluorescent probe fura 2. This rise in [Ca2+]i was abolished after removal of extracellular Ca2+ in the medium.Myricetin (50 μM) significantly increased TXB2 production both in aortic rings with and without endothelium and in BAEC. These increases were abolished both by Ca2+-free media and by indomethacin.Taken together, these results suggests that myricetin stimulates Ca2+ influx and subsequently triggers the activation of the PLA2 and cyclo-oxygenase pathways releasing TXA2 from the endothelium to contract rat aortic rings. The latter response occurs via the activation of Tp receptors on vascular smooth muscle cells. PMID:10455307

  14. Inability of HDL from type 2 diabetic patients to counteract the inhibitory effect of oxidised LDL on endothelium-dependent vasorelaxation.

    PubMed

    Perségol, L; Vergès, B; Foissac, M; Gambert, P; Duvillard, L

    2006-06-01

    In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by oxidised LDL. In type 2 diabetic patients, HDL are glycated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by oxidised LDL. Using rabbit aorta rings, we compared the ability of HDL from 16 type 2 diabetic patients and 13 control subjects to suppress the inhibition of vasodilation that is induced by oxidised LDL. Oxidised LDL inhibited endothelium-dependent vasodilation (maximal relaxation [Emax] = 58.2+/-14.6 vs 99.3+/-5.2% for incubation without any lipoprotein, p < 0.0001). HDL from control subjects significantly reduced the inhibitory effect of oxidised LDL on vasodilatation (Emax = 77.6+/-12.9 vs 59.5+/-7.7%, p < 0.001), whereas HDL from type 2 diabetic patients had no effect (Emax = 52.4+/-20.4 vs 57.2+/-18.7%, NS). HDL triglyceride content was significantly higher in type 2 diabetic patients than in control subjects (5.3+/-2.2 vs 3.1+/-1.4%, p < 0.01) and was highly inversely correlated to Emax for oxidised LDL+HDL in type 2 diabetic patients (r = -0.71, p < 0.005). In type 2 diabetes mellitus, the ability of HDL to counteract the inhibition of endothelium-dependent vasorelaxation induced by oxidised LDL is impaired and is inversely correlated with HDL triglyceride content. These findings suggest that HDL are less atheroprotective in type 2 diabetic patients than in control subjects.

  15. Involvement of endothelium-dependent and -independent mechanisms in midazolam-induced vasodilation.

    PubMed

    Colussi, Gian Luca; Di Fabio, Alessandro; Catena, Cristiana; Chiuch, Alessandra; Sechi, Leonardo A

    2011-08-01

    Benzodiazepine (BDZ) infusion has been shown to reduce blood pressure in both humans and animals. Although the inhibitory effects of BDZ on the central nervous system have been well documented, less is known about the direct effects of BDZ on the vascular bed. The aims of this study were to assess the effects of the BDZ midazolam on the vascular system in C57/BL6 mouse aortic rings and to investigate the mechanisms of its direct vascular action. We found that midazolam induced reversible, dose-dependent vasodilation in potassium- and phenylephrine-precontracted rings. In rings that were precontracted with potassium or phenylephrine, treatment with 10 μmol l(-1) midazolam increased vasodilation by 15 and 60%, respectively, compared with baseline. Vasodilation increased by 80 and 87%, respectively, after treatment with 50 μmol l(-1) midazolam. Only the low concentration of midazolam (10 μmol l(-1)) induced endothelium-dependent vasodilation in phenylephrine-precontracted rings. Vasodilation increased by 60% in rings with endothelium and by 20% in rings without endothelium. Conversely, only the high concentration of midazolam (50 μmol l(-1)) reduced the CaCl(2)-induced vasoconstriction of aortic rings with EC(50) (the concentration giving 50% of the maximal effect) values of 1 and 6 mmol l(-1) for vehicle- and midazolam-treated rings, respectively. Furthermore, the incubation of phenylephrine-precontracted rings with an inhibitor of the nitric oxide synthase (NOS) NG-nitro-L-arginine methyl ester or the inhibitors of central or peripheral type BDZ receptors (flumazenil or PK 11195, respectively) produced no change in midazolam-induced vasodilation. Thus, low concentrations of midazolam induce vasodilation via an endothelium-dependent mechanism that does not involve NO production. In contrast, high concentrations of midazolam induce vasodilation via an endothelium-independent mechanism that implies reduced sensitivity of aortic rings to calcium ions. Additionally

  16. Differential mechanisms for insulin-induced relaxations in mouse posterior tibial arteries and main mesenteric arteries.

    PubMed

    Qu, Dan; Liu, Jian; Lau, Chi Wai; Huang, Yu

    2014-12-01

    The characteristics of endothelium-dependent relaxations in response to insulin and acetylcholine (ACh) in the mouse posterior tibial artery (PTA) were studied on wire myograph, and compared to those in the mouse main mesenteric artery (MMA). Insulin-induced relaxation in PTA was reversed by PI3K and Akt inhibitors, LY294002 and triciribine, but not by nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) or guanylate cyclase inhibitor, ODQ. The relaxation in PTA was also inhibited by apamin (small-conductance Ca(2+)-activated K(+) channel blocker) plus charybdotoxin (intermediate-conductance Ca(2+)-activated K(+) channel blocker), elevated KCl or ouabain (Na(+)-K(+) ATPase inhibitor) plus BaCl(2) [inwardly rectifying K(+) (K(IR)) channel inhibitor]; whereas L-NAME but not triciribine inhibited ACh-induced relaxation in PTA. On the other hand, nitric oxide and endothelium-derived hyperpolarizing factor albeit to a less extent mediated both insulin- and ACh-induced relaxations in MMA. The present study is for the first time dissecting out the components of endothelium-dependent relaxation in mouse PTA and suggesting differential responses to different agonists in distinctive blood vessels.

  17. TRP channel Ca2+ sparklets: fundamental signals underlying endothelium-dependent hyperpolarization

    PubMed Central

    Sullivan, Michelle N.

    2013-01-01

    Important functions of the vascular endothelium, including permeability, production of antithrombotic factors, and control of vascular tone, are regulated by changes in intracellular Ca2+. The molecular identities and regulation of Ca2+ influx channels in the endothelium are incompletely understood, in part because of experimental difficulties associated with application of patch-clamp electrophysiology to native endothelial cells. However, advances in confocal and total internal reflection fluorescence microscopy and the development of fast, high-affinity Ca2+-binding fluorophores have recently allowed for direct visualization and characterization of single-channel transient receptor potential (TRP) channel Ca2+ influx events in endothelial cells. These events, called “TRP channel Ca2+ sparklets,” have been optically recorded from primary endothelial cells and the intact endothelium, and the biophysical properties and fundamental significance of these Ca2+ signals in vasomotor regulation have been characterized. This review will first briefly discuss the role of endothelial cell TRP channel Ca2+ influx in endothelium-dependent vasodilation, describe improved methods for recording unitary TRP channel activity using optical methods, and highlight discoveries regarding the regulation and physiological significance of TRPV4 Ca2+ sparklets in the vascular endothelium enabled by this new technology. Perspectives on the potential use of these techniques to evaluate changes in TRP channel Ca2+ influx activity associated with endothelial dysfunction are offered. PMID:24025865

  18. Circulating microparticles from patients with valvular heart disease and cardiac surgery inhibit endothelium-dependent vasodilation.

    PubMed

    Fu, Li; Hu, Xiao-Xia; Lin, Ze-Bang; Chang, Feng-Jun; Ou, Zhi-Jun; Wang, Zhi-Ping; Ou, Jing-Song

    2015-09-01

    Vascular function is very important for maintaining circulation after cardiac surgery. Circulating microparticles (MPs) generated in various diseases play important roles in causing inflammation, coagulation, and vascular injury. However, the impact of MPs generated from patients who have valvular heart disease (VHD), before and after cardiac surgery, on vascular function remains unknown. This study is designed to investigate the impact of such MPs on vasodilation. Microparticles were isolated from age-matched healthy subjects and patients who had VHD, before cardiac surgery, and at 12 hours and 72 hours afterward. The number of MPs was measured and compared. Effects evaluated were of the impact of MPs on: vasodilation of mice aorta; the phosphorylation and expression of Akt, endothelial nitric oxide synthase (eNOS), protein kinase C-βII (PKC-βII), and p70 ribosomal protein S6 kinase (p70S6K); expression of caveolin-1; the association of eNOS with heat shock protein 90 (HSP90); and generation of nitric oxide and superoxide anion of human umbilical vein endothelial cells. Compared with the healthy subjects, VHD patients had significantly higher levels of circulating MPs and those MPs before cardiac surgery can: impair endothelium-dependent vasodilation; inhibit phosphorylation of Akt and eNOS; increase activation of PKC-βII and p70S6K; enhance expression of caveolin-1; reduce the association of HSP90 with eNOS; decrease nitric oxide production, and increase superoxide anion generation. These deleterious effects were even stronger in postoperative MPs. Our data demonstrate that MPs generated from VHD patients before and after cardiac surgery contributed to endothelial dysfunction, by uncoupling and inhibiting eNOS. Circulating MPs are potential therapeutic targets for the maintenance of vascular function postoperatively. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  19. Adrenergic stimulation-released histamine taken-up in adrenergic nerves induces endothelium-dependent vasodilation in rat mesenteric resistance arteries.

    PubMed

    Haruki, Yuto; Takatori, Shingo; Hattori, Sayo; Zamami, Yoshito; Koyama, Toshihiro; Tangsucharit, Panot; Kawasaki, Hiromu

    2012-01-01

    The present study investigated whether histamine was taken up by perivascular adrenergic nerves and released by periarterial nerve stimulation (PNS) to induce vascular responses. In rat mesenteric vascular beds treated with capsaicin to eliminate calcitonin gene-related peptide (CGRP)ergic vasodilation and with active tone, PNS (1 - 4 Hz) induced only adrenergic nerve-mediated vasoconstriction. Histamine treatment for 20 min induced PNS-induced vasoconstriction followed by vasodilation without affecting CGRP-induced vasodilation. Chlorpheniramine, guanethidine, combination of histamine and desipramine, and endothelium-removal abolished PNS-induced vasodilation in histamine-treated preparations. These results suggest that histamine taken up by and released from adrenergic nerves by PNS causes endothelium-dependent vasodilation in rat mesenteric arteries.

  20. Blood pressure lowering effect of the extract of aerial parts of Capparis aphylla is mediated through endothelium-dependent and independent mechanisms.

    PubMed

    Shah, Abdul Jabbar; Gilani, Anwarul Hassan

    2011-01-01

    This investigation was aimed to provide pharmacological evidences for the medicinal use of Capparis aphylla in hypertension. In normotensive anesthetized rats, intravenous administration of the crude extract of Capparis aphylla (Ca.Cr; 3-100 mg/kg) caused a fall in mean arterial pressure (MAP), which was partially blocked in the presence of atropine (2 mg/kg). In isolated rabbit aortic rings, Ca.Cr inhibited phenylephrine (1 μM) and high K(+) (80 mM) precontractions with respective EC(50) values of 0.10 (0.07-0.15) and 1.22 mg/mL (1.00-1.50), suggesting calcium channel blocking (CCB) activity with a predominant inhibitory effect on receptor operated Ca(2+) channels. Pretreatment of the arotic rings with Ca.Cr (0.1-1 mg/mL) caused a rightward shift in the Ca(2+) concentration response curves, similar to verapamil. In isolated rat aorta preparations, Ca.Cr caused a partial endothelium-dependent L-NAME/atropine-sensitive vasodilator effect. In guinea-pig atria, Ca.Cr suppressed both rate and force of spontaneous atrial contractions with respective EC(50) values of 1.35 (1.01-1.79) and 1.60 mg/mL (1.18-2.17), which remained unchanged in the presence of atropine (1 μM). These data indicate that the blood pressure (BP) lowering effect of the crude extract of Capparis aphylla is mediated through a vasodilator and cardiac depressant effect. The vasodilator effect is partly mediated by an endothelium-dependent, atropine-sensitive NO pathway, while the CCB effect is partly responsible for endothelium-independent vasodilatation and also for the cardiac depressant effect; thus, this study provides pharmacologic evidence with respect to the medicinal use of the plant in hypertension.

  1. Variation in genes in the endothelin pathway and endothelium-dependent and endothelium-independent vasodilation in an elderly population.

    PubMed

    Lind, L; Syvänen, A-C; Axelsson, T; Lundmark, P; Hägg, S; Larsson, A

    2013-05-01

    Indirect evidences by blockade of the endothelin receptors have suggested a role of endothelin in endothelium-dependent vasodilation. This study aimed to investigate whether circulating levels of endotehlin-1 or genetic variations in genes in the endothelin pathway were related to endothelium-dependent vasodilation. In 1016 seventy-year-old participants of the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (52% women), we measured endothelium-dependent vasodilation using the invasive forearm technique with acetylcholine given in the brachial artery (EDV) and the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD). Plasma endothelin-1 levels were measured and 60 SNPs in genes in the endothelin pathway (ECE1, EDN1, EDNRA, EDNRB) were genotyped. No significant associations were found between circulating endothelin levels and EDV or FMD. No single genotype was related to EDV or FMD following adjustment for multiple testing, but a genotype score for 3 SNPs (rs11618266 in EDNRB, rs17675063 in EDNRA, rs3026868 in ECE1) was significantly related to EDV (beta coefficient 0.070, 95% CI 0.025-0.12, P = 0.002) when adjusting for gender, systolic blood pressure, HDL and LDL cholesterol, serum triglycerides, BMI, diabetes, smoking, antihypertensive medication or statins and CRP. This score was also related to nitroprusside-induced vasodilation in the forearm. A combination of genotypes in the endothelin pathway was related to both endothelium-dependent and endothelium-independent vasodilation in forearm resistance vessels, but not in the brachial artery in an elderly population, giving evidence for a role of the endothelin system in resistance vessel reactivity independent of major cardiovascular risk factors. Acta Physiologica © 2013 Scandinavian Physiological Society.

  2. Arginase II Deletion Increases Corpora Cavernosa Relaxation in Diabetic Mice

    PubMed Central

    Toque, Haroldo; Tostes, Rita; Yao, Lin; Xu, Zhimin; Webb, Clinton R.; Caldwell, Ruth; Caldwell, Robert

    2010-01-01

    Introduction Diabetes-induced erectile dysfunction involves elevated arginase (Arg) activity and expression. Because nitric oxide (NO) synthase and Arg share and compete for their substrate L-arginine, NO production is likely linked to regulation of Arg. Arg is highly expressed and implicated in erectile dysfunction. Aim It was hypothesized that Arg-II isoform deletion enhances relaxation function of corpora cavernosal (CC) smooth muscle in a streptozotocin (STZ) diabetic model. Methods Eight weeks after STZ-induced diabetes, vascular functional studies, Arg activity assay, and protein expression levels of Arg and constitutive NOS (using western blots) were assessed in CC tissues from non-diabetic wild type (WT), diabetic (D) WT (WT+D), Arg-II knockout (KO) and Arg-II KO+D mice (N=8–10 per group). Main Outcome Measures Inhibition or lack of arginase results in facilitation of CC relaxation in diabetic CC. Results Strips of CC from Arg-II KO mice exhibited an enhanced maximum endothelium-dependent relaxation (from 70+3% to 84+4%) and increased nitrergic relaxation (by 55%, 71%, 42%, 42%, and 24% for 1, 2, 4, 8 and 16 Hz, respectively) compared to WT mice. WT+D mice showed a significant reduction of endothelium-dependent maximum relaxation (44+8%), but this impairment of relaxation was significantly prevented in Arg-II KO+D mice (69+4%). Sympathetic-mediated and alpha-adrenergic agent-induced contractile responses also were increased in CC strips from D compared to non-D controls. Contractile responses were significantly lower in Arg-II KO control and D versus the WT groups. WT+D mice increased Arg activity (1.5-fold) and Arg-II protein expression and decreased total and phospho-eNOS at Ser-1177, and nNOS levels. These alterations were not seen in Arg-II KO mice. Additionally, the Arg inhibitor BEC (50 μM) enhanced nitrergic and endothelium-dependent relaxation in CC of WT+D mice. Conclusion These studies show for the first time that Arg-II deletion improves CC

  3. AGEs breaking and antioxidant treatment improves endothelium-dependent dilation without effect on flow-mediated remodeling of resistance arteries in old Zucker diabetic rats

    PubMed Central

    2014-01-01

    restored relaxation to the level found in LZ rats. Conclusions ALT-711 did not improve outward remodeling in mature ZDF rats but it reduced oxidative stress and consequently improved endothelium-dependent relaxation. In mature LZ rats, ALT-711 improved outward remodeling and reduced AGEs level. Consequently, AGEs breaking is differently useful in ageing whether it is associated with diabetes or not. PMID:24581152

  4. AGEs breaking and antioxidant treatment improves endothelium-dependent dilation without effect on flow-mediated remodeling of resistance arteries in old Zucker diabetic rats.

    PubMed

    Freidja, Mohamed L; Vessières, Emilie; Toutain, Bertrand; Guihot, Anne-Laure; Custaud, Marc-Antoine; Loufrani, Laurent; Fassot, Céline; Henrion, Daniel

    2014-03-03

    level found in LZ rats. ALT-711 did not improve outward remodeling in mature ZDF rats but it reduced oxidative stress and consequently improved endothelium-dependent relaxation. In mature LZ rats, ALT-711 improved outward remodeling and reduced AGEs level. Consequently, AGEs breaking is differently useful in ageing whether it is associated with diabetes or not.

  5. Kinetics of relaxation responses to vasorelaxants in isolated rabbit aorta.

    PubMed

    Wiener, H L; Murray, J M; Thalody, G P; Maayani, S

    1992-09-22

    Transient responses of isolated tissues to drugs are best studied by application of non-steady-state protocols in which the data collected are analyzed using kinetic models. The time dependence of the relaxation response of the adventitia- and endothelium-denuded rabbit aorta to four vasorelaxants (nitroglycerin, sodium nitroprusside, 5'-N-ethylcarboxamidoadenosine and isoproterenol) was analyzed by an exploratory kinetic model. A rapid relaxation (t1/2 = 1-3 min) was elicited by all vasorelaxants. An apparent desensitization or fade of the relaxation response to nitroglycerin or isoproterenol was visualized as the partial regaining of tissue tone (t1/2 = 2-3 min). The relaxation responses to sodium nitroprusside or 5'-N-ethylcarboxamidoadenosine were stable for at least 60 min and did not exhibit an apparent regaining of tension. Tissues rendered desensitized by either isoproterenol or nitroglycerin responded fully to sodium nitroprusside or 5'-N-ethylcarboxamidoadenosine. The rate constant for relaxation was vasorelaxant concentration-dependent and saturable for all vasorelaxants. For isoproterenol, nitroglycerin, and 5'-N-ethylcarboxamidoadenosine the rate constant for relaxation was inversely proportional to the contractile stimulus, as was the magnitude of relaxation for all vasorelaxants. Although the magnitude and rate constant of the fade was not concentration-dependent for isoproterenol, it was inversely proportional to the nitroglycerin concentration. The rate constant of the fade was proportional to the contractile stimulus for isoproterenol and nitroglycerin, and the magnitude of the fade was proportional to the contractile stimulus for nitroglycerin. We propose that kinetic studies of responses in isolated vasculature supersede studies performed under steady-state conditions, for they extend our knowledge of the manner by which the steady-state is achieved and allow for a quantitative analysis of the time-dependent changes which should assist in

  6. Exercise training enhances multiple mechanisms of relaxation in coronary arteries from ischemic hearts

    PubMed Central

    Deer, Rachel R.

    2013-01-01

    Exercise training of coronary artery disease patients is of considerable interest, since it has been shown to improve vascular function and, thereby, enhance blood flow into compromised myocardial regions. However, the mechanisms underlying exercise-induced improvements in vascular function have not been fully elucidated. We tested the hypothesis that exercise training increases the contribution of multiple mediators to endothelium-dependent relaxation of coronary arteries in the underlying setting of chronic coronary artery occlusion. To induce gradual occlusion, an ameroid constrictor was placed around the proximal left circumflex coronary artery in Yucatan miniature swine. At 8 wk postoperatively, pigs were randomly assigned to sedentary or exercise (treadmill, 5 days/wk) regimens for 14 wk. Exercise training significantly enhanced the contribution of nitric oxide, prostanoids, and large-conductance Ca2+-dependent K+ (BKCa) channels to endothelium-dependent, bradykinin-mediated relaxation in nonoccluded and collateral-dependent arteries. Combined nitric oxide synthase, prostanoid, and BKCa channel inhibition ablated the enhanced relaxation associated with exercise training. Exercise training significantly increased nitric oxide levels in response to bradykinin in endothelial cells isolated from nonoccluded and collateral-dependent arteries. Bradykinin treatment significantly increased PGI2 levels in all artery treatment groups and tended to be further enhanced after nitric oxide synthase inhibition in exercise-trained pigs. No differences were found in whole cell BKCa channel currents, BKCa channel protein levels, or arterial cyclic nucleotide levels. Although redundant, upregulation of parallel vasodilator pathways appears to contribute to enhanced endothelium-dependent relaxation, potentially providing a more refined control of blood flow after exercise training. PMID:23997097

  7. Relationships between three different tests to evaluate endothelium-dependent vasodilation and cardiovascular risk in a middle-aged sample.

    PubMed

    Lind, Lars

    2013-08-01

    For a couple of decades, flow-mediated vasodilation in the brachial artery (FMD) and acetylcholine-mediated vasodilation in the forearm (EDV) have been used to assess endothelium-dependent vasodilation. During recent years a third technique, peripheral artery tonometry (PAT) using EndoPat, has been introduced. We now aimed to investigate the relationships between these techniques, and their relation to cardiovascular risk. In the population-based Prospective investigation of Obesity, Energy and Metabolism (POEM) study conducted in individuals all aged 50 years (50% women), EDV, FMD and the reactive hyperemia index were measured in the first 222 individuals. Cardiovascular risk was assessed by the Framingham risk score. No significant relationships were seen between the three different tests to evaluate endothelium-dependent vasodilation. EDV (r = -0.21, P = 0.004) and FMD (r = -0.19, P = 0.004), but not PAT were significantly related to the Framingham score in an inverse way. Also sodium nitroprusside-mediated vasodilation in the forearm, reflecting endothelium-independent vasodilation (EIDV), was related to the Framingham score in an inverse way (r = -0.30, P < 0.0001). No close relationships were seen between the three tests of endothelium-dependent vasodilation, suggesting that they each contribute with unique information on vasoreactivity. EDV, EIDV and FMD, but not PAT, were related to the Framingham score, suggesting that vasoreactivity in some vascular beds are related to cardiovascular risk in middle-aged individuals.

  8. Effect of ascorbic acid on endothelium-dependent vasodilatation of human arterial conduits for coronary artery bypass grafting.

    PubMed

    Mangoush, Omar; Nakamura, Koki; Al-Ruzzeh, Sharif; Athanasiou, Thanos; Chester, Adrian; Amrani, Mohamed

    2003-10-01

    Techniques aimed at improving the performance of arterial conduits will maximize the clinical benefit achievable with coronary artery bypass surgery. Controlling oxidant stress could be a strategy for preventing early graft deterioration. We tested the effect of a free radical scavenger, ascorbic acid (vitamin C), on preserving the endothelium-dependent vasodilatation function in vitro of radial artery and internal thoracic artery. We also tested its effect on the amount of reactive oxygen species (ROS) generated by each graft. Radial artery (RA, n=25) and internal thoracic (ITA, n=19) segments were obtained from coronary artery bypass grafting patients. Each segment was divided into 3-4 mm vascular rings and incubated with or without ascorbic acid (10(-3) mol/l) for 1 h or 72 h. Using the organ bath technique, the endothelium-dependent vasodilatation function was tested in vitro by the addition of cumulative concentrations of acetylcholine (10(-9)-10(-5) mol/l) following vasocontraction by endothelin-1 (3 x 10(-8) mol/l). ROS were measured by using chemiluminescence technique at 1-h and after 72 h incubation with or without ascorbic acid. There were no differences in the vasodilatation function between control and ascorbic acid group of both arteries in the 1-hour incubation experiment. However, in the 72 h incubation experiment, ascorbic acid preserved the endothelium-dependent vasodilatation function of RA compared with control group (35.8+/-2.2% vs. 25.9+/-2.1%; P=0.005), but not ITA (39+/-3.5% vs. 40.5+/-9.3%; P=0.438). After 72 h incubation, RA generated significantly more free radicals compared with 1 h (133.7+/-151.5 vs. 16.8+/-16.8 cps/mg x 100; P=0.01); however, AA has no statistically significant effect on decreasing the amount of free radicals generated by both arteries. In RA, ascorbic acid is able to preserve the endothelium-dependent vasodilatation function after 72 h incubation, but not after 1 h. However, the mechanism of action of AA is not

  9. An endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium-dependent vasodilator in resistance vessels of wild-type and endothelial NO synthase knockout mice

    PubMed Central

    Brandes, Ralf P.; Schmitz-Winnenthal, Friedrich-Hubertus; Félétou, Michel; Gödecke, Axel; Huang, Paul L.; Vanhoutte, Paul M.; Fleming, Ingrid; Busse, Rudi

    2000-01-01

    In addition to nitric oxide (NO) and prostacyclin (PGI2), the endothelium generates the endothelium-derived hyperpolarizing factor (EDHF). We set out to determine whether an EDHF-like response can be detected in wild-type (WT) and endothelial NO synthase knockout mice (eNOS −/−) mice. Vasodilator responses to endothelium-dependent agonists were determined in vivo and in vitro. In vivo, bradykinin induced a pronounced, dose-dependent decrease in mean arterial pressure (MAP) which did not differ between WT and eNOS −/− mice and was unaffected by treatment with Nω-nitro-l-arginine methyl ester and diclofenac. In the saline-perfused hindlimb of WT and eNOS −/− mice, marked Nω-nitro-l-arginine (l-NA, 300 μmol/liter)- and diclofenac-insensitive vasodilations in response to both bradykinin and acetylcholine (ACh) were observed, which were more pronounced than the agonist-induced vasodilation in the hindlimb of WT in the absence of l-NA. This endothelium-dependent, NO/PGI2-independent vasodilatation was sensitive to KCl (40 mM) and to the combination of apamin and charybdotoxin. Gap junction inhibitors (18α-glycyrrhetinic acid, octanol, heptanol) and CB-1 cannabinoid-receptor agonists (Δ9-tetrahydrocannabinol, HU210) impaired EDHF-mediated vasodilation, whereas inhibition of cytochrome P450 enzymes, soluble guanylyl cyclase, or adenosine receptors had no effect on EDHF-mediated responses. These results demonstrate that in murine resistance vessels the predominant agonist-induced endothelium-dependent vasodilation in vivo and in vitro is not mediated by NO, PGI2, or a cytochrome P450 metabolite, but by an EDHF-like principle that requires functional gap junctions. PMID:10944233

  10. Repetition of ischemic preconditioning augments endothelium-dependent vasodilation in humans: role of endothelium-derived nitric oxide and endothelial progenitor cells.

    PubMed

    Kimura, Masashi; Ueda, Keiko; Goto, Chikara; Jitsuiki, Daisuke; Nishioka, Kenji; Umemura, Takashi; Noma, Kensuke; Yoshizumi, Masao; Chayama, Kazuaki; Higashi, Yukihito

    2007-06-01

    Several studies have shown that both early and late effects of ischemic preconditioning (IPC) protect against myocardial injury after ischemic reperfusion. The purpose of this study was to evaluate the late effects of IPC on endothelial function in humans. Late phase of IPC was induced by upper limb ischemia (cuff inflation of over 200 mm Hg for 5 minutes) 6 times a day for 1 month. We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh) and to sodium nitroprusside (SNP) before and after IPC stimulus in 30 young healthy men. FBF was measured using a strain-gauge plethysmograph. The IPC stimulus significantly increased plasma concentration of vascular endothelial growth factor (VEGF), circulating level of endothelial progenitor cells (EPCs), and FBF responses to ACh, but these did not change in the control group. The FBF responses to SNP were similar before and after the IPC stimulus. Infusion of N(G)-monomethyl-L-arginine, a nitric oxide synthase inhibitor, completely eliminated the IPC stimulus-induced augmentation of FBF responses to ACh. In the contralateral arms of subjects that received the IPC stimulus, FBF responses to ACh did not change, but levels of VEGF and circulating EPCs increased. These findings suggest that repetition of late IPC stimulus augments endothelium-dependent vasodilation in humans through increases in nitric oxide production and number of EPCs under a local condition. Repetition of IPC stimulus may be a simple, safe, and feasible therapeutic technique for endothelial protection of peripheral vessels.

  11. [Changes in endothelium-dependent dilation and α1-adrenoreactivity of rat aorta caused by inducible NO-synthase inhibition after motor activity restrictions].

    PubMed

    Solodkov, A P; Iatskovskaia, N M

    2013-07-01

    The aim of work was to study the influence of the highly selective blocker of the inducible NO-synthase (iNOS) of S-methylthiourea on the alteration of the endothelium-dependent vasodilation and α1-adrenoreactivity of the isolated rat aortic rings which underwent a short-term restriction of physical activity. The experiments were carried out on rat aortic rings preparations from female-rats bathed in Krebs-Henseleit solution, bubbled with 95% O2 and 5% CO2 and contracting in isometric mode. Endothelium-dependent dilation was caused by cumulative addition of acetylcholine (10-(10)-10(-4) M) after phenylephrine precontraction(10(-6) M). Adrenoreactivity was assessed through the response to increasing concentrations of α1-adrenergic receptor agonist. The 60-minute immobilization stress, characterized by the increase of the relative weight of the adrenal glands by 19.5%, the concentration of glucocorticoids (twice as much), of NO2/NO3 (stable NO degradation products) by 35%, the reduction in the level of thyroxine (by 16%), triiodothyronine (by 10%) and the increase in thyrotropic hormone by 45%, interleukin-1b (twice as much) and the appearance of tumour necrosis factor alpha in the blood serum, was accompanied by the two types of reaction of isolated aortic rings to acetylcholine and phenylephrine. The first one was expressed in the enhancing of acetylcholine-induced dilation of isolated aortic rings and the reduction of its response to α1-adrenergic stimulant phenylephrine. The second one showed a decrease in the response of isolated aortic rings to acetylcholine and enhancing the response to phenylephrine. But both of these reaction types were eliminated by using highly selective inducible NO-synthase inhibitor with S-methylisothiourea. However, it was differently directed with a different type of reaction. Taken together, these results suggest that the iNOS is formed in the cells of rat aorta under short-term stress. In some cases it can be a source of a large

  12. Fetal responses to induced maternal relaxation during pregnancy

    PubMed Central

    DiPietro, Janet A.; Costigan, Kathleen A.; Nelson, Priscilla; Gurewitsch, Edith D.; Laudenslager, Mark L.

    2008-01-01

    Fetal responses to induced maternal relaxation during the 32nd week of pregnancy were recorded in 100 maternal-fetal pairs using a digitized data collection system. The 18-minute guided imagery relaxation manipulation generated significant changes in maternal heart rate, skin conductance, respiration period, and respiratory sinus arrhythmia. Significant alterations in fetal neurobehavior were observed, including decreased fetal heart rate (FHR), increased FHR variability, suppression of fetal motor activity (FM), and increased FM-FHR coupling. Attribution of the two fetal cardiac responses to the guided imagery procedure itself, as opposed to simple rest or recumbency, is tempered by the observed pattern of response. Evaluation of correspondence between changes within individual maternal-fetal pairs revealed significant associations between maternal autonomic measures and fetal cardiac patterns, lower umbilical and uterine artery resistance and increased FHR variability, and declining salivary cortisol and FM activity. Potential mechanisms that may mediate the observed results are discussed. PMID:17919804

  13. Plasma myeloperoxidase is inversely associated with endothelium-dependent vasodilation in elderly subjects with abnormal glucose metabolism.

    PubMed

    van der Zwan, Leonard P; Teerlink, Tom; Dekker, Jacqueline M; Henry, Ronald M A; Stehouwer, Coen D A; Jakobs, Cornelis; Heine, Robert J; Scheffer, Peter G

    2010-12-01

    Myeloperoxidase (MPO), a biomarker related to inflammation, oxidative stress, and nitric oxide scavenging, has been shown to impair endothelium-dependent vasodilation. Because elevated hydrogen peroxide concentrations in diabetic vessels may enhance MPO activity, we hypothesized that a stronger association of MPO with flow-mediated dilation (FMD) may be found in subjects with abnormal glucose metabolism. Myeloperoxidase concentrations were measured in EDTA plasma samples from participants of a population-based cohort study, including 230 subjects with normal glucose metabolism and 386 with abnormal glucose metabolism. Vascular function was expressed as FMD and nitroglycerin-mediated dilation of the brachial artery. In subjects with abnormal glucose metabolism, MPO was negatively associated with FMD (-20.9 [95% confidence interval {CI}, -41.7 to -0.2] -μm change in FMD per SD increment of MPO). This association remained significant after adjustment for nitroglycerin-mediated dilation (-31.1 [95% CI, -50.0 to -12.3]) and was not attenuated after further adjustment for established risk factors. In subjects with normal glucose metabolism, MPO was not significantly associated with FMD (2.0 [95% CI, -16.0 to 20.0]). In conclusion, in subjects with abnormal glucose metabolism, plasma levels of MPO are inversely associated with endothelium-dependent vasodilation, possibly reflecting enhancement of MPO activity by vascular oxidative stress.

  14. Effect of taurine deficiency on adenosine receptor-mediated relaxation of the rat aorta.

    PubMed

    Abebe, Worku; Mozaffari, Mahmood S

    2003-11-01

    We recently demonstrated that chronic taurine supplementation or deficiency causes alterations in reactivity of the rat aorta to several vasoactive agents. In the present investigation, we examined the effects beta-alanine-induced endogenous taurine deficiency on the mechanical responsiveness of the isolated rat aorta to adenosine receptor stimulation with 2-chloroadenosine (CAD), 5'-N-ethylcarboxyamidoadenosine (NECA), and N(6)-cyclopentyladenosine (CPA). The adenosine analogs produced concentration-dependent (1 x 10(-9)-3 x 10(-3) M) relaxations of aortas from both control and beta-alanine-treated rats with the rank order of potencies NECA>CAD>CPA, which was consistent with A(2) receptor identification. CAD and NECA induced both endothelium-dependent and -independent relaxations of the aortas. The endothelium-dependent responses to both agents and the independent responses to CAD were significantly attenuated by beta-alanine treatment. The relaxation responses of the aortas from control and taurine-deficient rats to CAD and NECA were markedly antagonized by ZM241385 (10(-5) M), suggesting the involvement of A(2A) adenosine receptors. Further, N-nitro-L-arginine methyl ester (L-NAME; 10(-5) M) significantly attenuated the endothelium-mediated relaxation produced by CAD and NECA in both groups. However, the inhibitory effect of L-NAME was less on the beta-alanine-treated tissues, providing evidence that the effect of taurine deficiency was linked to a reduction in nitric oxide generation. As in the aorta, CAD produced both endothelium-dependent and -independent relaxation responses in the rat superior mesenteric artery, and both responses were inhibited by chronic beta-alanine treatment, suggesting that not only similar responses can be generated by a given adenosine agonist in different vascular beds, but also beta-alanine treatment modulates these responses. On the other hand, while CPA elicited only endothelium-independent aortic relaxation, this response was

  15. Vascular microRNA-204 is remotely governed by the microbiome and impairs endothelium-dependent vasorelaxation by downregulating Sirtuin1

    PubMed Central

    Vikram, Ajit; Kim, Young-Rae; Kumar, Santosh; Li, Qiuxia; Kassan, Modar; Jacobs, Julia S.; Irani, Kaikobad

    2016-01-01

    Gut microbiota promotes atherosclerosis, and vascular endothelial dysfunction, signalled by impaired endothelium-dependent vasorelaxation, is an early marker of atherosclerosis. Here we show that vascular microRNA-204 (miR-204) expression is remotely regulated by the microbiome, and impairs endothelial function by targeting the Sirtuin1 lysine deacetylase (Sirt1). MiR-204 is downregulated, while Sirt1 is upregulated, in aortas of germ-free mice. Suppression of gut microbiome with broad-spectrum antibiotics decreases miR-204, increases Sirt1 and bioavailable vascular nitric oxide, and improves endothelium-dependent vasorelaxation in mouse aortas. Antibiotics curtail aortic miR-204 upregulation, and rescue decline of aortic Sirt1 and endothelium-dependent vasorelaxation, triggered by high-fat diet feeding. Improvement of endothelium-dependent vasorelaxation by antibiotics is lost in mice lacking endothelial Sirt1. Systemic antagonism of miR-204 rescues impaired endothelium-dependent vasorelaxation and vascular Sirt1, and decreases vascular inflammation induced by high-fat diet. These findings reveal a gut microbe-vascular microRNA–Sirtuin1 nexus that leads to endothelial dysfunction. PMID:27586459

  16. Leptin-Induced Endothelium-Dependent Vasorelaxation of Peripheral Arteries in Lean and Obese Rats: Role of Nitric Oxide and Hydrogen Sulfide

    PubMed Central

    Jamroz-Wiśniewska, Anna; Gertler, Arieh; Solomon, Gili; Wood, Mark E.; Whiteman, Matthew; Bełtowski, Jerzy

    2014-01-01

    Adipose tissue hormone leptin induces endothelium-dependent vasorelaxation mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing factors (EDHF). Previously it has been demonstrated that in short-term obesity the NO-dependent and the EDHF-dependent components of vascular effect of leptin are impaired and up-regulated, respectively. Herein we examined the mechanism of the EDHF-dependent vasodilatory effect of leptin and tested the hypothesis that alterations of acute vascular effects of leptin in obesity are accounted for by chronic hyperleptinemia. The study was performed in 5 groups of rats: (1) control, (2) treated with exogenous leptin for 1 week to induce hyperleptinemia, (3) obese, fed highly-palatable diet for 4 weeks, (4) obese treated with pegylated superactive rat leptin receptor antagonist (PEG-SRLA) for 1 week, (5) fed standard chow and treated with PEG-SRLA. Acute effect of leptin on isometric tension of mesenteric artery segments was measured ex vivo. Leptin relaxed phenylephrine-preconstricted vascular segments in NO- and EDHF-dependent manner. The NO-dependent component was impaired and the EDHF-dependent component was increased in the leptin-treated and obese groups and in the latter group both these effects were abolished by PEG-SRLA. The EDHF-dependent vasodilatory effect of leptin was blocked by either the inhibitor of cystathionine γ-lyase, propargylglycine, or a hydrogen sulfide (H2S) scavenger, bismuth (III) subsalicylate. The results indicate that NO deficiency is compensated by the up-regulation of EDHF in obese rats and both effects are accounted for by chronic hyperleptinemia. The EDHF-dependent component of leptin-induced vasorelaxation is mediated, at least partially, by H2S. PMID:24475175

  17. Leptin-induced endothelium-dependent vasorelaxation of peripheral arteries in lean and obese rats: role of nitric oxide and hydrogen sulfide.

    PubMed

    Jamroz-Wiśniewska, Anna; Gertler, Arieh; Solomon, Gili; Wood, Mark E; Whiteman, Matthew; Bełtowski, Jerzy

    2014-01-01

    Adipose tissue hormone leptin induces endothelium-dependent vasorelaxation mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing factors (EDHF). Previously it has been demonstrated that in short-term obesity the NO-dependent and the EDHF-dependent components of vascular effect of leptin are impaired and up-regulated, respectively. Herein we examined the mechanism of the EDHF-dependent vasodilatory effect of leptin and tested the hypothesis that alterations of acute vascular effects of leptin in obesity are accounted for by chronic hyperleptinemia. The study was performed in 5 groups of rats: (1) control, (2) treated with exogenous leptin for 1 week to induce hyperleptinemia, (3) obese, fed highly-palatable diet for 4 weeks, (4) obese treated with pegylated superactive rat leptin receptor antagonist (PEG-SRLA) for 1 week, (5) fed standard chow and treated with PEG-SRLA. Acute effect of leptin on isometric tension of mesenteric artery segments was measured ex vivo. Leptin relaxed phenylephrine-preconstricted vascular segments in NO- and EDHF-dependent manner. The NO-dependent component was impaired and the EDHF-dependent component was increased in the leptin-treated and obese groups and in the latter group both these effects were abolished by PEG-SRLA. The EDHF-dependent vasodilatory effect of leptin was blocked by either the inhibitor of cystathionine γ-lyase, propargylglycine, or a hydrogen sulfide (H2S) scavenger, bismuth (III) subsalicylate. The results indicate that NO deficiency is compensated by the up-regulation of EDHF in obese rats and both effects are accounted for by chronic hyperleptinemia. The EDHF-dependent component of leptin-induced vasorelaxation is mediated, at least partially, by H2S.

  18. Nitric oxide is a mediator of tachykinin NK3 receptor-induced relaxation in rat mesenteric artery.

    PubMed Central

    Mizuta, A.; Takano, Y.; Honda, K.; Saito, R.; Matsumoto, T.; Kamiya, H.

    1995-01-01

    1. The mechanism of vasodilatation induced by tachykinin peptides was studied in isolated mesenteric arteries of rats. 2. Senktide, a selective NK3 agonist, elicited potent endothelium-dependent relaxation of arteries precontracted with phenylephrine (10(-5) M), but an NK1 agonist did not. 3. A non-peptide NK3 antagonist, SR 142801, inhibited senktide-induced relaxation. However, a non-peptide NK1 antagonist, CP-96,345, and a peptide-based NK2 antagonist, L-659,877, had no effect on senktide-induced relaxation. 4. N omega-nitro-L-arginine (L-NOARG), a nitric oxide synthesis inhibitor, markedly attenuated the relaxant response to senktide. 5. These results suggest that the endothelium of rat mesenteric arteries possesses tachykinin NK3 receptors, and that NK3 agonist-induced vasodilatation is mediated by release of nitric oxide (NO) from the endothelium. PMID:8680725

  19. Endothelium-dependent and -independent vasorelaxant actions and mechanisms induced by total flavonoids of Elsholtzia splendens in rat aortas.

    PubMed

    Wang, Hui-Ping; Lu, Jian-Feng; Zhang, Guo-Lin; Li, Xu-Yun; Peng, Hong-Yun; Lu, Yuan; Zhao, Liang; Ye, Zhi-Guo; Bruce, Iain C; Xia, Qiang; Qian, Ling-Bo

    2014-09-01

    Elsholtzia splendens (ES) is, rich in flavonoids, used to repair copper contaminated soil in China, which has been reported to benefit cardiovascular systems as folk medicine. However, few direct evidences have been found to clarify the vasorelaxation effect of total flavonoids of ES (TFES). The vasoactive effect of TFES and its underlying mechanisms in rat thoracic aortas were investigated using the organ bath system. TFES (5-200mg/L) caused a concentration-dependent vasorelaxation in endothelium-intact rings, which was not abolished but significantly reduced by the removal of endothelium. The nitric oxide synthase (NOS) inhibitor N(ω)-nitro-l-arginine methyl ester (100μM) and the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,2-α]quinoxalin-1-one (30μM) significantly blocked the endothelium-dependent vasorelaxation of TFES. Meanwhile, NOS activity in endothelium-intact aortas was concentration-dependently elevated by TFES. However, indomethacin (10μM) did not affect TFES-induced vasorelaxation. Endothelium-independent vasorelaxation of TFES was significantly attenuated by KATP channel blocker glibenclamide. The accumulative Ca(2+)-induced contraction in endothelium-denuded aortic rings primed with KCl or phenylephrine was markedly weakened by TFES. These results revealed that the NOS/NO/cGMP pathway is likely involved in the endothelium-dependent vasorelaxation induced by TFES, while activating KATP channel, inhibiting intracellular Ca(2+) release, blocking Ca(2+) channels and decreasing Ca(2+) influx into vascular smooth muscle cells might contribute to the endothelium-independent vasorelaxation conferred by TFES.

  20. Acute Retinal Ischemia Inhibits Endothelium-Dependent Nitric Oxide–Mediated Dilation of Retinal Arterioles via Enhanced Superoxide Production

    PubMed Central

    Ren, Yi; Potts, Luke B.; Yuan, Zhaoxu; Kuo, Enoch; Rosa, Robert H.; Kuo, Lih

    2012-01-01

    Purpose. 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. Methods. 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. Results. 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. Conclusions. 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. PMID:22110081

  1. The development of a patient-centered program based on the relaxation response: the Relaxation Response Resiliency Program (3RP).

    PubMed

    Park, Elyse R; Traeger, Lara; Vranceanu, Ana-Maria; Scult, Matthew; Lerner, Jonathan A; Benson, Herbert; Denninger, John; Fricchione, Gregory L

    2013-01-01

    Chronic daily stress has significant physical, emotional, and financial implications; levels of stress are increasing in the US. Dr. Benson highlighted how the mind and body function together in one's experience of the stress response and proposed the existence of the relaxation response (RR). The current paper describes the foundation and development of an 8-session multimodal treatment program for coping with chronic stress: the Relaxation Response Resiliency Program (3RP). We review the past decades of RR research, outline the development of the 3RP treatment, and provide an overview of the program's theory and content. Extensive research and clinical work have examined how eliciting the RR may combat stress through down-regulation of the sympathetic nervous system. Related to this work are the multidimensional constructs of resiliency and allostatic load. The 3RP is based on principles from the fields of stress management, cognitive-behavioral therapy, and positive psychology, and has three core target areas: (1) elicitation of the RR; (2) stress appraisal and coping; and (3) growth enhancement. An 8-week patient-centered treatment program has been developed, with the purpose of assisting patients with a variety of psychological and medical issues to better cope with chronic stress. Mastery of the RR is theorized to maximize one's ability to benefit from multimodal mind body strategies. The goal of the 3RP is to enhance individuals' adaptive responses to chronic stress through increasing awareness and decreasing the physiological, emotional, cognitive, and behavioral effects of the stress response, while simultaneously promoting the effects of being in the RR. Copyright © 2013 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  2. Homocysteine-induced attenuation of vascular endothelium-dependent hyperalgesia in the rat

    PubMed Central

    Joseph, Elizabeth K.; Green, Paul G.; Ferrari, Luiz F.; Levine, Jon D.

    2014-01-01

    We have recently demonstrated a role of the vascular endothelium in peripheral pain mechanism by disrupting endothelial cell function using intravascular administration of octoxynol-9, a non-selective membrane active agent. As an independent test of the role of endothelial cells in pain mechanisms, we evaluated the effect of homocysteine, an agent that damages endothelial cell function. Mechanical stimulus-induced enhancement of endothelin-1 hyperalgesia in the gastrocnemius muscle of the rat was first prevented then enhanced by intravenous administration of homocysteine, but was only inhibited by its precursor, methionine. Both homocysteine and methionine significantly attenuated mechanical hyperalgesia in two models of ergonomic muscle pain, induced by exposure to vibration, and by eccentric exercise, and cutaneous mechanical hyperalgesia in an ischemia-reperfusion injury model of Complex Regional Pain Syndrome type I, all previously shown responsive to octoxynol-9. This study provides independent support for a role of the endothelial cell in pain syndromes thought to have a vascular basis, and suggests that substances that are endothelial cell toxins can enhance vascular pain. PMID:25451284

  3. Effects of Buddhism walking meditation on depression, functional fitness, and endothelium-dependent vasodilation in depressed elderly.

    PubMed

    Prakhinkit, Susaree; Suppapitiporn, Siriluck; Tanaka, Hirofumi; Suksom, Daroonwan

    2014-05-01

    The objectives of this study were to determine the effects of the novel Buddhism-based walking meditation (BWM) and the traditional walking exercise (TWE) on depression, functional fitness, and vascular reactivity. This was a randomized exercise intervention study. The study was conducted in a university hospital setting. Forty-five elderly participants aged 60-90 years with mild-to-moderate depressive symptoms were randomly allocated to the sedentary control, TWE, and BWM groups. The BWM program was based on aerobic walking exercise incorporating the Buddhist meditations performed 3 times/week for 12 weeks. Depression score, functional fitness, and endothelium-dependent vasodilation as measured by the flow-mediated dilation (FMD) were the outcome measures used. Muscle strength, flexibility, agility, dynamic balance, and cardiorespiratory endurance increased in both exercise groups (p<0.05). Depression score decreased (p<0.05) only in the BWM group. FMD improved (p<0.05) in both exercise groups. Significant reduction in plasma cholesterol, triglyceride, high-density lipoprotein cholesterol, and C-reactive protein were found in both exercise groups, whereas low-density lipoprotein cholesterol, cortisol, and interleukin-6 concentrations decreased only in the BWM group. Buddhist walking meditation was effective in reducing depression, improving functional fitness and vascular reactivity, and appears to confer greater overall improvements than the traditional walking program.

  4. Parallel decrease in arterial distensibility and in endothelium-dependent dilatation in young women with a history of pre-eclampsia.

    PubMed

    Pàez, Olga; Alfie, José; Gorosito, Marta; Puleio, Pablo; de Maria, Marcelo; Prieto, Noemì; Majul, Claudio

    2009-10-01

    Pre-eclampsia not only complicates 5 to 8% of pregnancies but also increases the risk of maternal cardiovascular disease and mortality later in life. We analyzed three different aspects of arterial function (pulse wave velocity, augmentation index, and flow-mediated dilatation), in 55 nonpregnant, normotensive women (18-33 years old) according to their gestational history: 15 nulliparous, 20 with a previous normotensive, and 20 formerly pre-eclamptic pregnancy. Former pre-eclamptic women showed a significantly higher augmentation index and pulse wave velocity (P < 0.001 and P < 0.05, respectively) and lower flow-mediated dilatation (p = 0.01) compared to control groups. In contrast, sublingual nitroglycerine elicited a comparable vasodilatory response in the three groups. The augmentation index correlated significantly with pulse wave velocity and flow-mediated dilatation (R = 0.28 and R = -0.32, respectively, P < 0.05 for both). No significant correlations were observed between augmentation index or flow-mediated dilatation with age, body mass index (BMI), brachial blood pressure, heart rate, or metabolic parameters (plasma cholesterol, glucose, insulin, or insulin resistance). Birth weight maintained a significantly inverse correlation with the augmentation index (R = -0.51, p < 0.002) but not with flow-mediated dilatation. Our findings revealed a parallel decrease in arterial distensibility and endothelium-dependent dilatation in women with a history of pre-eclampsia compared to nulliparous women and women with a previous normal pregnancy. A high augmentation index was the most consistent alteration associated with a history of pre-eclampsia. The study supports the current view that the generalized arterial dysfunction associated with pre-eclampsia persists subclinically after delivery.

  5. Regulation of KCa2.3 and endothelium-dependent hyperpolarization (EDH) in the rat middle cerebral artery: the role of lipoxygenase metabolites and isoprostanes.

    PubMed

    Gauthier, Kathryn M; Campbell, William B; McNeish, Alister J

    2014-01-01

    Background and Purpose. In rat middle cerebral arteries, endothelium-dependent hyperpolarization (EDH) is mediated by activation of calcium-activated potassium (KCa) channels specifically KCa2.3 and KCa3.1. Lipoxygenase (LOX) products function as endothelium-derived hyperpolarizing factors (EDHFs) in rabbit arteries by stimulating KCa2.3. We investigated if LOX products contribute to EDH in rat cerebral arteries. Methods. Arachidonic acid (AA) metabolites produced in middle cerebral arteries were measured using HPLC and LC/MS. Vascular tension and membrane potential responses to SLIGRL were simultaneously recorded using wire myography and intracellular microelectrodes. Results. SLIGRL, an agonist at PAR2 receptors, caused EDH that was inhibited by a combination of KCa2.3 and KCa3.1 blockade. Non-selective LOX-inhibition reduced EDH, whereas inhibition of 12-LOX had no effect. Soluble epoxide hydrolase (sEH) inhibition enhanced the KCa2.3 component of EDH. Following NO synthase (NOS) inhibition, the KCa2.3 component of EDH was absent. Using HPLC, middle cerebral arteries metabolized (14)C-AA to 15- and 12-LOX products under control conditions. With NOS inhibition, there was little change in LOX metabolites, but increased F-type isoprostanes. 8-iso-PGF2α inhibited the KCa2.3 component of EDH. Conclusions. LOX metabolites mediate EDH in rat middle cerebral arteries. Inhibition of sEH increases the KCa2.3 component of EDH. Following NOS inhibition, loss of KCa2.3 function is independent of changes in LOX production or sEH inhibition but due to increased isoprostane production and subsequent stimulation of TP receptors. These findings have important implications in diseases associated with loss of NO signaling such as stroke; where inhibition of sEH and/or isoprostane formation may of benefit.

  6. Regulation of KCa2.3 and endothelium-dependent hyperpolarization (EDH) in the rat middle cerebral artery: the role of lipoxygenase metabolites and isoprostanes

    PubMed Central

    Gauthier, Kathryn M.; Campbell, William B.

    2014-01-01

    Background and Purpose. In rat middle cerebral arteries, endothelium-dependent hyperpolarization (EDH) is mediated by activation of calcium-activated potassium (KCa) channels specifically KCa2.3 and KCa3.1. Lipoxygenase (LOX) products function as endothelium-derived hyperpolarizing factors (EDHFs) in rabbit arteries by stimulating KCa2.3. We investigated if LOX products contribute to EDH in rat cerebral arteries. Methods. Arachidonic acid (AA) metabolites produced in middle cerebral arteries were measured using HPLC and LC/MS. Vascular tension and membrane potential responses to SLIGRL were simultaneously recorded using wire myography and intracellular microelectrodes. Results. SLIGRL, an agonist at PAR2 receptors, caused EDH that was inhibited by a combination of KCa2.3 and KCa3.1 blockade. Non-selective LOX-inhibition reduced EDH, whereas inhibition of 12-LOX had no effect. Soluble epoxide hydrolase (sEH) inhibition enhanced the KCa2.3 component of EDH. Following NO synthase (NOS) inhibition, the KCa2.3 component of EDH was absent. Using HPLC, middle cerebral arteries metabolized 14C-AA to 15- and 12-LOX products under control conditions. With NOS inhibition, there was little change in LOX metabolites, but increased F-type isoprostanes. 8-iso-PGF2α inhibited the KCa2.3 component of EDH. Conclusions. LOX metabolites mediate EDH in rat middle cerebral arteries. Inhibition of sEH increases the KCa2.3 component of EDH. Following NOS inhibition, loss of KCa2.3 function is independent of changes in LOX production or sEH inhibition but due to increased isoprostane production and subsequent stimulation of TP receptors. These findings have important implications in diseases associated with loss of NO signaling such as stroke; where inhibition of sEH and/or isoprostane formation may of benefit. PMID:24949235

  7. The endothelium-dependent vasodilator action of a new beverage made of red wine vinegar and grape juice.

    PubMed

    Takahara, Akira; Sugiyama, Atsushi; Honsho, Sachiko; Sakaguchi, Yasue; Akie, Yasuki; Nakamura, Yuji; Hashimoto, Keitaro

    2005-04-01

    A new non-alcoholic beverage made of red wine vinegar and grape juice (Budo-no-megumi) has been recently demonstrated to lower the blood pressure of human as well as rats. In this study, we pharmacologically analyzed the mechanism of its hypotensive action. The thoracic aorta with intact endothelium was isolated from Sprague-Dawley rats, and incubated with a Tyrode's solution. The beverage in concentrations of 0.25 to 2% relaxed the pre-contracted aorta with an alpha-adrenoceptor agonist phenylephrine in a concentration-dependent manner, 2% of which induced 59% relaxation. In contrast, the vasodilator response disappeared in the aorta without endothelium. L-Nitro-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, significantly reduced the vasodilator effect of the beverage, whereas indomethacin, an inhibitor of cyclooxygenase, hardly affected it. These results suggest that the beverage can activate the nitric oxide synthase activity to exert vasodilation, which may partly explain its previously reported hypotensive action.

  8. Endothelium-dependent increase in vascular sensitivity to phenylephrine in long-term streptozotocin diabetic rat aorta.

    PubMed Central

    Chang, K. S.; Stevens, W. C.

    1992-01-01

    1. The effect of short- and long-term streptozotocin (STZ)-induced diabetes (12 and 52 weeks) on the vascular response to phenylephrine was examined in the isolated thoracic aorta with and without intact endothelium from diabetic, age matched control rats and diabetic rats treated with insulin. 2. Twelve weeks after induction of diabetes, aortae with intact endothelium demonstrated no changes either in sensitivity (defined as pD2) or contractility (defined as the maximal developed tension per aortic tissue wet weight) to phenylephrine. 3. In contrast, 52 weeks after induction of diabetes, aortae with intact endothelium demonstrated an increased sensitivity to phenylephrine while contractility to phenylephrine was not changed. Insulin treatment partially corrected the increased sensitivity to phenylephrine observed in diabetic rat aorta. 4. Removal of endothelium abolished the difference in phenylephrine sensitivity between diabetic and control aortae at 52 weeks. 5. Pretreatment of intact aortae with methylene blue, an inhibitor of endothelium-derived relaxing factor (EDRF), abolished the difference in phenylephrine sensitivity between control and diabetic rat aortae at 52 weeks, while pretreatment with indomethacin, an inhibitor of cyclo-oxygenase, had no effect. These results suggest that decreases in production or release of EDRF might be responsible for the increased vascular sensitivity to phenylephrine observed in long-term STZ diabetic rats. 6. Acetylcholine-induced relaxation, which is EDRF-dependent, was less in diabetic rat aortae with intact endothelium at 52 weeks, but not at 12 weeks. These results further support the theory that decreases in capacity of the endothelium to synthesize or release EDRF may occur in long-term STZ diabetic rats. PMID:1467844

  9. CYP epoxygenase-derived H2O2 is involved in the endothelium-derived hyperpolarization (EDH) and relaxation of intrarenal arteries.

    PubMed

    Muñoz, Mercedes; López-Oliva, Maria Elvira; Pinilla, Estéfano; Martínez, María Pilar; Sánchez, Ana; Rodríguez, Claudia; García-Sacristán, Albino; Hernández, Medardo; Rivera, Luis; Prieto, Dolores

    2017-05-01

    Reactive oxygen species (ROS) like hydrogen peroxide (H2O2) are involved in the in endothelium-derived hyperpolarization (EDH)-type relaxant responses of coronary and mesenteric arterioles. The role of ROS in kidney vascular function has mainly been investigated in the context of harmful ROS generation associated to kidney disease. The present study was sought to investigate whether H2O2 is involved in the endothelium-dependent relaxations of intrarenal arteries as well the possible endothelial sources of ROS generation involved in these responses. Under conditions of cyclooxygenase (COX) and nitric oxide (NO) synthase inhibition, acetylcholine (ACh) induced relaxations and stimulated H2O2 release that were reduced by catalase and by the glutathione peroxidase (GPx) mimetic ebselen in rat renal interlobar arteries, suggesting the involvement of H2O2 in the endothelium-dependent responses. ACh relaxations were also blunted by the CYP2C inhibitor sulfaphenazole and by the NADPH oxidase inhibitor apocynin. Acetylcholine stimulated both superoxide (O2(•-)) and H2O2 production that were reduced by sulfaphenazole and apocynin. Expression of the antioxidant enzyme CuZnSOD and of the H2O2 reducing enzymes catalase and GPx-1 was found in both intrarenal arteries and renal cortex. On the other hand, exogenous H2O2 relaxed renal arteries by decreasing vascular smooth muscle (VSM) intracellular calcium concentration [Ca(2+)]i and markedly enhanced endothelial KCa currents in freshly isolated renal endothelial cells. CYP2C11 and CYP2C23 epoxygenases were highly expressed in interlobar renal arteries and renal cortex, respectively, and were co-localized with eNOS in renal endothelial cells. These results demonstrate that H2O2 is involved in the EDH-type relaxant responses of renal arteries and that CYP 2C epoxygenases are physiologically relevant endothelial sources of vasodilator H2O2 in the kidney. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Academic Performance among Middle-School Students after Exposure to a Relaxation Response Curriculum.

    ERIC Educational Resources Information Center

    Benson, Herbert; Wilcher, Marilyn; Greenberg, Beth; Huggins, Erica; Ennis, Margaret; Zuttermeister, Patricia C.; Myers, Patricia; Friedman, Richard

    2000-01-01

    Examined the relationship between middle school students' exposure to a relaxation response curriculum and academic achievement over time. Teachers were trained to teach relaxation response exercises. Data on students' grade point average (GPA), work habits, cooperation, and attendance indicated that students exposed to more than two semesters of…

  11. Propofol-induced relaxation of rat aorta is altered by aging.

    PubMed

    Sakai, Yoko; Kawahito, Shinji; Takaishi, Kazumi; Mita, Naoji; Kinoshita, Hiroyuki; Hatakeyama, Noboru; Azma, Toshiharu; Nakaya, Yutaka; Kitahata, Hiroshi

    2014-01-01

    Propofol causes vasodilation via endothelium-dependent and -independent mechanisms. Because endothelial function is impaired with aging, the effects of propofol on endothelium-dependent vasodilation might be altered by aging. The aim of this study was thus to determine the effects of aging on vascular responses to propofol. Young (4-6 weeks old) or adult (16-25 weeks old) rats were anesthetized with sevoflurane. The thoracic aorta was dissected and cut into pieces 3-4 mm in length. In some rings, the endothelium was deliberately removed. The ring segment of the aorta was mounted for isometric force recording at a resting tension of 0.5-1.0 g in a 2 ml organ bath, containing Krebs-Ringer bicarbonate buffer. Arteries were precontracted with phenylephrine, and the function of endothelium was confirmed with acetylcholine. Then, we studied the concentration-dependent effects of propofol in endothelium-intact (control group) and -denuded aortic rings (denuded group), as well as those treated with N(ω)-nitro-L-arginine methylester (L-NAME group). Relaxation due to propofol was observed in the control groups of both young and adult rats in a concentration-dependent manner, but the magnitude of relaxation was significantly greater in young rats. In addition, in young rats, relaxation due to propofol was significantly and equally reduced in both L-NAME and denuded groups at all propofol concentrations that we studied (10(-6)-10(-3) M). In adult rats, relaxation due to propofol was quite similar between control and L-NAME groups at all propofol concentrations, whereas it was significantly reduced in the denuded group. These results suggest that endothelium-derived nitric oxide plays an important role in propofol-induced vasodilation in young rats, but not in adult rats.

  12. Fetal response to abbreviated relaxation techniques. A randomized controlled study.

    PubMed

    Fink, Nadine S; Urech, Corinne; Isabel, Fornaro; Meyer, Andrea; Hoesli, Irène; Bitzer, Johannes; Alder, Judith

    2011-02-01

    stress during pregnancy can have adverse effects on the course of pregnancy and on fetal development. There are few studies investigating the outcome of stress reduction interventions on maternal well-being and obstetric outcome. this study aims (1) to obtain fetal behavioral states (quiet/active sleep, quiet/active wakefulness), (2) to investigate the effects of maternal relaxation on fetal behavior as well as on uterine activity, and (3) to investigate maternal physiological and endocrine parameters as potential underlying mechanisms for maternal-fetal relaxation-transferral. the behavior of 33 fetuses was analyzed during laboratory relaxation/quiet rest (control group, CG) and controlled for baseline fetal behavior. Potential associations between relaxation/quiet rest and fetal behavior (fetal heart rate (FHR), FHR variation, FHR acceleration, and body movements) and uterine activity were studied, using a computerized cardiotocogram (CTG) system. Maternal heart rate, blood pressure, cortisol, and norepinephrine were measured. intervention (progressive muscle relaxation, PMR, and guided imagery, GI) showed changes in fetal behavior. The intervention groups had higher long-term variation during and after relaxation compared to the CG (p=.039). CG fetuses had more FHR acceleration, especially during and after quiet rest (p=.027). Women in the PMR group had significantly more uterine activity than women in the GI group (p=.011) and than CG women. Maternal heart rate, blood pressure, and stress hormones were not associated with fetal behavior. this study indicates that the fetus might participate in maternal relaxation and suggests that GI is superior to PMR. This could especially be true for women who tend to direct their attention to body sensations such as abdominal activity. 2010 Elsevier Ltd. All rights reserved.

  13. Endothelium-dependent vasodilator and antioxidant properties of a novel enzymatic extract of grape pomace from wine industrial waste.

    PubMed

    Rodriguez-Rodriguez, Rosalia; Justo, Maria Luisa; Claro, Carmen Maria; Vila, Elisabet; Parrado, Juan; Herrera, Maria Dolores; Alvarez de Sotomayor, Maria

    2012-12-01

    The aim of the present study was to evaluate the vascular effects of an enzymatic extract of grape pomace (GP-EE) on isolated arteries, focusing our attention on endothelium-derived relaxation and on its antioxidant properties. Grape pomace derived from wine making was extracted by an enzymatic process and its composition of polyphenols was evaluated by HPLC and ESI-MS/MS, detecting kaempferol, catechin, quercetin and procyanidins B1 and B2, trace levels of resveratrol and tracing out gallocatechin and anthocyanidins. GP-EE induced endothelium- and NO-dependent vasodilatation of both rat aorta and small mesenteric artery (SMA) segments and reduced Phe-induced response in aortic rings. Both ORAC and DPPH assays confirmed antioxidant scavenging properties of GP-EE, which also prevented O(2)(·-) production (assessed by DHE fluorescence) and contraction elicited by ET-1. These results provide evidence that GP-EE possesses interesting antioxidant and protective vascular properties and highlight the potential interest of this extract as a functional food.

  14. Fatty acids impair endothelium-dependent vasorelaxation: a link between obesity and arterial stiffness in very old Zucker rats.

    PubMed

    Sloboda, Natacha; Fève, Bruno; Thornton, Simon N; Nzietchueng, Rosine; Regnault, Véronique; Simon, Ginny; Labat, Carlos; Louis, Huguette; Max, Jean-Pierre; Muscat, Adeline; Osborne-Pellegrin, Mary; Lacolley, Patrick; Benetos, Athanase

    2012-09-01

    To analyze age-related interactions between obesity, its associated metabolic disorders, and macrocirculation, we studied large artery stiffness and fatty acid responsiveness in lean and obese Zucker rats, aged 25 (adult) and 80 weeks (very old). Systolic arterial pressure was higher in old obese than in old lean rats (178 ± 10 vs 134 ± 8 mmHg, respectively). Carotid elastic modulus-wall stress curves showed increased age-dependent arterial stiffening, which was greater in obese animals. Old obese exhibited endothelial dysfunction with increased systemic oxidative stress. Adult obese had elevated plasma free fatty acid levels (1,866 ± 177 vs 310 ± 34 μg/μL in lean animals). In old obese, linoleate and palmitate increased contractility to phenylephrine and reduced relaxation to acetylcholine. Thus, obesity at 25 weeks appears to trigger accelerated arterial aging observed at 80 weeks. The early increase in free fatty acids may be a key effector in the severe arterial stiffness of the aged obese Zucker model.

  15. Chronic moderate hypoxia and protein malnutrition both induce growth retardation, but have distinct effects on arterial endothelium-dependent reactivity in the chicken embryo.

    PubMed

    Ruijtenbeek, Karin; Kessels, Lilian C G A; De Mey, Jo G R; Blanco, Carlos E

    2003-04-01

    Deviations in the rate of intrauterine growth may change organ system development, resulting in cardiovascular disease in adult life. Arterial endothelial dysfunction often plays an important role in these diseases. The effects of two interventions that reduce fetal growth, chronic hypoxia and protein malnutrition, on arterial endothelial function were investigated. Eggs of White Leghorn chickens were incubated either in room air or in 15% O2 from d 6 until d 19 of the 21-d incubation. Protein malnutrition was induced by removal of 10% of the total albumen content at d 0. In vitro reactivity of the femoral artery in response to vasodilators was measured at d 19. Both chronic hypoxia and protein malnutrition reduced embryonic body weight at d 19 by 14% without affecting relative brain weight. Chronic hypoxia or protein malnutrition did not change sensitivity to the exogenous nitric oxide donor, sodium nitroprusside (5.74 +/- 0.15 versus 5.85 +/- 0.23 and 6.05 +/- 0.18 versus 6.01 +/- 0.34, respectively). Whereas protein malnutrition did not modify arterial sensitivity to acetylcholine (7.00 +/- 0.10 versus 7.12 +/- 0.05), chronic hypoxia reduced sensitivity to this endothelium-dependent vasodilator (6.57 +/- 0.07 versus 7.02 +/- 0.06). In the presence of Nomega-nitro-l-arginine methyl ester, this difference in sensitivity to acetylcholine was no longer apparent (6.31 +/- 0.13 versus 6.27 +/- 0.06), indicating that chronic exposure to hypoxia reduced sensitivity to acetylcholine by lowering nitric oxide release. In additional experiments, a decrease in basal nitric oxide release in arteries of 3- to 4-wk-old chickens that had been exposed to in ovo chronic hypoxia was observed (increase in K+ contraction: -0.16 +/- 0.33 N/m versus 0.68 +/- 020 N/m). Protein malnutrition and chronic hypoxia both induce disproportionate growth retardation, but only the latter impairs arterial endothelial function. Intrauterine exposure to chronic hypoxia induces changes in arterial

  16. Unaltered caffeine-induced relaxation in the aorta of stroke-prone spontaneously hypertensive rats (SHRSP).

    PubMed

    Sekiguchi, Fumiko; Miyake, Yoshimasa; Kashimoto, Takafumi; Sunano, Satoru

    2002-04-01

    Caffeine-induced relaxation was studied in aortic segments from Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Although acetylcholine-induced endothelium-dependent relaxation was impaired in preparations from SHRSP, the relaxation induced by caffeine was identical in both groups. In addition, caffeine-induced relaxation was not affected by removal of the endothelium in either group. The relaxation induced by N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (db-cAMP), a membrane-permeable analog of adenosine 3':5'-cyclic monophosphate (cAMP), was identical in both groups. No significant difference was observed in the increase in cAMP content induced by caffeine in the aortic smooth muscle between the groups, although the basal content was significantly higher in preparations from SHRSP. These results suggest that the relaxation induced by caffeine in these preparations is brought about by its direct effect on smooth muscle and that the response of the smooth muscle to caffeine, including cAMP production, is not altered in preparations from SHRSP compared with those from WKY.

  17. Upregulation of SK3 and IK1 Channels Contributes to the Enhanced Endothelial Calcium Signaling and the Preserved Coronary Relaxation in Obese Zucker Rats

    PubMed Central

    Climent, Belén; Moreno, Laura; Martínez, Pilar; Contreras, Cristina; Sánchez, Ana; Pérez-Vizcaíno, Francisco; García-Sacristán, Albino; Rivera, Luis; Prieto, Dolores

    2014-01-01

    Background and Aims Endothelial small- and intermediate-conductance KCa channels, SK3 and IK1, are key mediators in the endothelium-derived hyperpolarization and relaxation of vascular smooth muscle and also in the modulation of endothelial Ca2+ signaling and nitric oxide (NO) release. Obesity is associated with endothelial dysfunction and impaired relaxation, although how obesity influences endothelial SK3/IK1 function is unclear. Therefore we assessed whether the role of these channels in the coronary circulation is altered in obese animals. Methods and Results In coronary arteries mounted in microvascular myographs, selective blockade of SK3/IK1 channels unmasked an increased contribution of these channels to the ACh- and to the exogenous NO- induced relaxations in arteries of Obese Zucker Rats (OZR) compared to Lean Zucker Rats (LZR). Relaxant responses induced by the SK3/IK1 channel activator NS309 were enhanced in OZR and NO- endothelium-dependent in LZR, whereas an additional endothelium-independent relaxant component was found in OZR. Fura2-AM fluorescence revealed a larger ACh-induced intracellular Ca2+ mobilization in the endothelium of coronary arteries from OZR, which was inhibited by blockade of SK3/IK1 channels in both LZR and OZR. Western blot analysis showed an increased expression of SK3/IK1 channels in coronary arteries of OZR and immunohistochemistry suggested that it takes place predominantly in the endothelial layer. Conclusions Obesity may induce activation of adaptive vascular mechanisms to preserve the dilator function in coronary arteries. Increased function and expression of SK3/IK1 channels by influencing endothelial Ca2+ dynamics might contribute to the unaltered endothelium-dependent coronary relaxation in the early stages of obesity. PMID:25302606

  18. Effects of relaxation and stress on the capsaicin-induced local inflammatory response.

    PubMed

    Lutgendorf, S; Logan, H; Kirchner, H L; Rothrock, N; Svengalis, S; Iverson, K; Lubaroff, D

    2000-01-01

    Although stress is known to modulate the inflammatory response, there has been little experimental examination of the effects of stress and stress reduction on inflammation in humans. In particular, the effects of stress and relaxation on neurogenic inflammation have been minimally studied. This study examines the effects of three experimental manipulations: mental stress, relaxation, and control on the local inflammatory response evoked by the intradermal injection of capsaicin, the active ingredient in chili peppers. Fifty subjects (28 men and 22 women) were pretrained in relaxation using an imagery-based relaxation tape and then randomized to experimental condition. Subjects participated in an evening reactivity session including 20 minutes of a stress (Stroop test), relaxation (tape), or control (video) manipulation, followed by a capsaicin injection in the forearm. Digitized flare measurements were taken for 1 hour postcapsaicin, and measurements of cardiovascular variables, cortisol, adrenocorticotrophic hormone, and norepinephrine were taken at regular intervals. The size of the maximum capsaicin-induced flare was significantly smaller in the relaxation condition than in the stress or control conditions, which did not differ from each other. Increases in norepinephrine, heart rate, and systolic blood pressure during the experimental task, but not after capsaicin, significantly predicted size of maximum flare and total area under the curve of flare measurements. These findings suggest that stress reduction may affect local inflammatory processes. Results are consistent with sympathetic modulation of the effects of relaxation on the flare response.

  19. Identification of structural relaxation in the dielectric response of water

    DOE PAGES

    Hansen, Jesper S.; Kisliuk, Alexander; Sokolov, Alexei P.; ...

    2016-06-09

    One century ago pioneering dielectric results obtained for water and n-alcohols triggered the advent of molecular rotation diffusion theory considered by Debye to describe the primary dielectric absorption in these liquids. Here, comparing dielectric, viscoelastic, and light scattering results, we unambiguously demonstrate that the structural relaxation appears only as a high-frequency shoulder in the dielectric spectra of water. In contrast, the main dielectric peak is related to a supramolecular structure, analogous to the Debye-like peak observed in monoalcohols.

  20. Identification of structural relaxation in the dielectric response of water

    SciTech Connect

    Hansen, Jesper S.; Kisliuk, Alexander; Sokolov, Alexei P.; Gainaru, Catalin

    2016-06-09

    One century ago pioneering dielectric results obtained for water and n-alcohols triggered the advent of molecular rotation diffusion theory considered by Debye to describe the primary dielectric absorption in these liquids. Here, comparing dielectric, viscoelastic, and light scattering results, we unambiguously demonstrate that the structural relaxation appears only as a high-frequency shoulder in the dielectric spectra of water. In contrast, the main dielectric peak is related to a supramolecular structure, analogous to the Debye-like peak observed in monoalcohols.

  1. The EGCg-induced redox-sensitive activation of endothelial nitric oxide synthase and relaxation are critically dependent on hydroxyl moieties.

    PubMed

    Auger, Cyril; Kim, Jong-Hun; Chabert, Philippe; Chaabi, Mehdi; Anselm, Eric; Lanciaux, Xavier; Lobstein, Annelise; Schini-Kerth, Valérie B

    2010-02-26

    Several rich sources of polyphenols stimulate the endothelial formation of nitric oxide (NO), a potent vasoprotecting factor, via the redox-sensitive activation of the PI3-kinase/Akt pathway leading to the phosphorylation of endothelial NO synthase (eNOS). The present study examined the molecular mechanism underlying the stimulatory effect of epicatechins on eNOS. NO-mediated relaxation was assessed using porcine coronary artery rings in the presence of indomethacin, and charybdotoxin plus apamin, inhibitors of cyclooxygenases and EDHF-mediated responses, respectively. The phosphorylation level of Akt and eNOS was assessed in cultured coronary artery endothelial cells by Western blot, and ROS formation using dihydroethidine. (-)-Epigallocatechin-3-O-gallate (EGCg) caused endothelium-dependent relaxations in coronary artery rings and the phosphorylation of Akt and eNOS in endothelial cells. These responses were inhibited by membrane-permeant analogues of superoxide dismutase and catalase, whereas native superoxide dismutase, catalase and inhibitors of major enzymatic sources of reactive oxygen species including NADPH oxidase, xanthine oxidase, cytochrome P450 and the mitochondrial respiration chain were without effect. The EGCg derivative with all hydroxyl functions methylated induced neither relaxations nor the intracellular formation of ROS, whereas both responses were observed when the hydroxyl functions on the gallate moiety were present. In conclusion, EGCg causes endothelium-dependent NO-mediated relaxations of coronary artery rings through the Akt-dependent activation of eNOS in endothelial cells. This response is initiated by the intracellular formation of superoxide anions and hydrogen peroxide, and is critically dependent on the gallate moiety and on the presence of hydroxyl functions possibly through intracellular auto-oxidation. Copyright 2010 Elsevier Inc. All rights reserved.

  2. Endothelium-dependent vasodilation is related to the occurrence of cortical brain infarcts at MR imaging: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.

    PubMed

    Lind, Lars; Nylander, Ruta; Johansson, Lars; Kullberg, Joel; Ahlström, Håkan; Larsson, Elna-Marie

    2017-03-01

    Infarcts in the brain can be divided into larger cortical and smaller deep lacunar infarcts. The pathogenesis differs between these two types of infarctions. This study aims to investigate the relationship between measures of endothelium-dependent vasodilation (EDV) and occurrence of cortical and lacunar infarcts in a population-based sample. In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, 1016 subjects aged 70 were evaluated by the invasive forearm technique with acetylcholine (EDV) and brachial artery ultrasound to assess flow-mediated vasodilation (FMD). Six to seven years later MRI of the brain was performed, and the prevalence of cortical and lacunar infarcts was visually assessed in 407 randomly selected subjects. Lacunar infarcts were found in 22% and cortical infarcts in 5·9% of the subjects. EDV and FMD were both significantly related to the occurrence of cortical, but not lacunar infarcts. In a model adjusting for gender, waist circumference, body mass index, fasting blood glucose, systolic and diastolic blood pressure, HDL and LDL cholesterol, serum triglycerides, smoking, antihypertensive treatment and statin use, both EDV and FMD were independent predictors of cortical infarcts (P = 0·035 and P = 0·008, respectively). Endothelium-dependent vasodilation in both forearm resistance vessels and the brachial artery was related to the occurrence of cortical, but not lacunar, infarcts at MRI in a population-based sample independently of traditional risk factors. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  3. Immune modulation in response to stress and relaxation.

    PubMed

    Mahbub-E-Sobhani; Haque, N; Salma, U; Ahmed, A

    2011-03-15

    Traditional medical science has kept the mind separate from the body. Recently people realize the effect of mind on health and psychoneuroimmunology is the new evolved science that describes the interactions between psyche and soma. In this review through a typical psycho-neuro-endocrino-immune network the effects of psychological stress (acute, brief naturalistic and chronic) and relaxation on immune modulation has been shown. From this network Corticotrophin Releasing Factor (CRF), Adrenocorticotrophic Hormone (ACTH), Glucocorticoids (GC), alpha-endorphin and Met-enkephalin are found as important endocrine components and T cells, B cells, monocytes/macrophages, Natural Killer (NK) cells and their cytokines that is Tumor Necrosis Factor-alpha (TNF-alpha), Interferon Gamma (IFN-alpha) and interleukins such as IL-1, IL-2, IL-4, IL-6, IL-10, IL-12 etc. are found as important immune components. Finally, it has been shown that, acute, brief naturalistic and chronic stress have different immune modulatory activities which are harmful to one's homeostasis and relaxation can help to maintain that homeostasis.

  4. Atomistic modeling of electron relaxation effect on femtosecond laser-induced thermoelastic response of gold films

    NASA Astrophysics Data System (ADS)

    Xiong, Q. L.; Tian, X. G.; Lu, T. J.

    2012-07-01

    The thermoelastic response of thin gold films induced by femtosecond laser irradiation is numerically simulated using a modified combined two-temperature model (TTM) and molecular dynamics (MD) method, with focus placed upon the influence of the electron relaxation effect. The validity of the numerical approach is checked against existing experimental results. While the electron relaxation effect is found negligible when the laser duration is much longer than the electron thermal relaxation time, it becomes significant if the laser duration matches the electron relaxation time, especially when the former is much shorter than the latter. The characteristics of thermo-mechanical interaction in the thin film are analyzed, and the influence of temperature-dependent material properties upon the thermoelastic response of the film quantified.

  5. Highly relaxing gadolinium based MRI contrast agents responsive to Mg2+ sensing.

    PubMed

    Abada, Sabah; Lecointre, Alexandre; Elhabiri, Mourad; Esteban-Gómez, David; Platas-Iglesias, Carlos; Tallec, Gaylord; Mazzanti, Marinella; Charbonnière, Loïc J

    2012-04-28

    A Gd complex based on a polyphosphonated pyridyl ligand shows a very high stability in aqueous solution (log K(EuL) = 25.7), a high relaxivity (8.5 mM(-1) s(-1) at 25 °C and 20 MHz) and a marked and selective relaxivity enhancement (37%) in the presence of Mg(2+), opening interesting perspectives for the design of cation responsive contrast agents.

  6. Vascular Tone Regulation Induced by C-Type Natriuretic Peptide: Differences in Endothelium-Dependent and -Independent Mechanisms Involved in Normotensive and Spontaneously Hypertensive Rats

    PubMed Central

    Caniffi, Carolina; Cerniello, Flavia M.; Gobetto, María N.; Sueiro, María L.; Arranz, Cristina

    2016-01-01

    Given that the role of C-type natriuretic peptide (CNP) in the regulation of vascular tone in hypertensive states is unclear, we hypothesized that impaired response of the nitric oxide system to CNP in spontaneously hypertensive rats (SHR) could affect vascular relaxation induced by the peptide in this model of hypertension, and that other endothelial systems or potassium channels opening could also be involved. We examined the effect of CNP on isolated SHR aortas, and the hindlimb vascular resistance (HVR) in response to CNP administration compared to normotensive rats. Aortas were mounted in an isometric organ bath and contracted with phenylephrine. CNP relaxed arteries in a concentration-dependent manner but was less potent in inducing relaxation in SHR. The action of CNP was diminished by removal of the endothelium, inhibition of nitric oxide synthase by Nω-nitro-L-arginine methyl ester, and inhibition of soluble guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one in both groups. In contrast, blockade of cyclooxygenase or subtype 2 bradykinin receptor increased CNP potency only in SHR. In both Wistar and SHR, CNP relaxation was blunted by tetraethylammonium and partially inhibited by BaCl2 and iberiotoxin, indicating that it was due to opening of the Kir and BKCa channels. However, SHR seem to be more sensitive to Kir channel blockade and less sensitive to BKCa channel blockade than normotensive rats. In addition, CNP decreases HVR in Wistar and SHR, but the effect of CNP increasing blood flow was more marked in SHR. We conclude that CNP induces aorta relaxation by activation of the nitric oxide system and opening of potassium channels, but the response to the peptide is impaired in conductance vessel of hypertensive rats. PMID:27936197

  7. Response to induced relaxation during pregnancy: comparison of women with high versus low levels of anxiety.

    PubMed

    Alder, Judith; Urech, Corinne; Fink, Nadine; Bitzer, Johannes; Hoesli, Irene

    2011-03-01

    Relaxation exercises have become a standard intervention for individuals with anxiety disorders but little is known about their potential for anxiety relief during pregnancy. The purpose of this study was to examine psychoendocrine (i) baseline differences and (ii) changes after a standardized relaxation period in pregnant women with high versus low levels of anxiety. Thirty-nine third-trimester high and low anxious pregnant women performed active or passive relaxation while levels of anxiety, hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adrenal-medullary (SAM) system activity were assessed before and after the relaxation period. In women with high levels of trait anxiety, state anxiety (F(1,36) = 8.3, p = .007) and negative affect (F(1,36) = 7.99, p = .008) as well as ACTH (F(1,35) = 9.24, p = .002) remained elevated over the entire course of the experimental procedure, the last indicating increased HPA axis activity. In addition, norepinephrine showed a constricted decrease of relaxation reflecting lower response of the SAM-system (F(1,37) = 4.41, p = .043). Although relaxation exercises have become a standard intervention for individuals with anxiety, pregnant women with high levels of trait anxiety benefited less than women with low levels from a single standardized relaxation period.

  8. Atmospheric Wind Relaxations and the Oceanic Response in the California Current Large Marine Ecosystem

    NASA Astrophysics Data System (ADS)

    Fewings, M. R.; Dorman, C. E.; Washburn, L.; Liu, W.

    2010-12-01

    On the West Coast of North America in summer, episodic relaxation of the upwelling-favorable winds causes warm water to propagate northward from southern to central California, against the prevailing currents [Harms and Winant 1998, Winant et al. 2003, Melton et al. 2009]. Similar wind relaxations are an important characteristic of coastal upwelling ecosystems worldwide. Although these wind relaxations have an important influence on coastal ocean dynamics, no description exists of the regional atmospheric patterns that lead to wind relaxations in southern California, or of the regional ocean response. We use QuikSCAT wind stress, North American Regional Reanalysis atmospheric pressure products, water temperature and velocity from coastal ocean moorings, surface ocean currents from high-frequency radars, and MODIS satellite sea-surface temperature and ocean color images to analyze wind relaxation events and the ocean response. We identify the events based on an empirical index calculated from NDBC buoy winds [Melton et al. 2009]. We describe the regional evolution of the atmosphere from the Gulf of Alaska to Baja California over the few days leading up to wind relaxations, and the coastal ocean temperature, color, and current response off southern and central California. We analyze ~100 wind relaxation events in June-September during the QuikSCAT mission, 1999-2009. Our results indicate south-central California wind relaxations in summer are tied to mid-level atmospheric low-pressure systems that form in the Gulf of Alaska and propagate southeastward over 3-5 days. As the low-pressure systems reach southern California, the atmospheric pressure gradient along the coast weakens, causing the surface wind stress to relax to near zero. The weak wind signal appears first at San Diego and propagates northward. QuikSCAT data indicate the relaxed winds extend over the entire Southern California Bight and up to 200 km offshore of central California. Atmospheric dynamics in

  9. Polymer dewetting via stimuli responsive structural relaxation-contact angle analysis.

    PubMed

    Ma, Xiumin; Crombez, Rene; Ashaduzzaman, Md; Kunitake, Masashi; Slater, Lisa; Mourey, Thomas; Texter, John

    2011-10-07

    Thin films of a stimuli-responsive homopolymer dewet as a stimulus response after anion exchange of the imidazolium's counter anion. Contact angle analysis and interfacial energy considerations indicate dewetting goes counter to increasing spreading coefficient. Intrafilm stress arising from structural relaxation drives the dewetting. This journal is © The Royal Society of Chemistry 2011

  10. The Effects of Behavior Therapy, Self-Relaxation, and Transcendental Meditation on Cardiovascular Stress Response.

    ERIC Educational Resources Information Center

    Puente, Antonio E.; Beiman, Irving

    1980-01-01

    Compared Behavior Therapy (BT), self-relaxation (SR), transcendental meditation (TM), and a waiting-list control group (WL) on measures of cardiovascular and subjective stress response. Results indicate that BT and SR were more effective than either TM or WL in reducing cardiovascular stress response. (Author)

  11. Endothelium-dependent and BRL 34915-induced vasodilatation in rat isolated perfused mesenteric arteries: role of G-proteins, K+ and calcium channels.

    PubMed Central

    Adeagbo, A. S.; Malik, K. U.

    1990-01-01

    1. In the isolated perfused, noradrenaline (NA)-constricted mesenteric arteries of the rat, acetylcholine (0.003-1 nmol), histamine (0.01-10 nmol) and the calcium ionophore A23187 (0.01-1 nmol), caused endothelium-dependent vasodilatation while the vasodilatation by the K+ channel activator BRL 34915 (0.1-1 nmol) was independent of endothelium. 2. The guanylate cyclase inhibitor, methylene blue at 10 microM did not inhibit the action of any of the vasodilators but at 50 microM reduced the vasodilator effect of acetylcholine (ACh), histamine and A23187. 3. Infusion of ouabain or perfusion with K(+)-free or excess K+ (50 mM) Krebs solution reduced the vasodilator effect of ACh, histamine and A23187, suggesting the action of these agents involves, at least in part, activation of Na+/K(+)-ATPase. The vasodilator effect of BRL 34915 was not affected by ouabain, but abolished during perfusion with Krebs solution containing excess K+ or depleted of K+. 4. Five structurally distinct K+ channel blockers (apamin, crude scorpion venom, procaine, quinidine and tetraethylammonium) attenuated the vasodilator effect of ACh, histamine and A23187. The K+ channel blockers, except apamin and crude scorpion venom, also inhibited the vasodilatation produced by BRL 34915. 5. The vasodilator effect of ACh, histamine or A23187 was not altered in mesenteric vessels of pertussis toxin-treated rats, suggesting that the K+ channels associated with the endothelium-dependent vasodilator effect of these agents are either not coupled to G-proteins or are coupled to G-proteins that are insensitive to pertussis toxin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2167732

  12. Response delay caused by dielectric relaxation of polymer insulators for organic transistors and resolution method

    NASA Astrophysics Data System (ADS)

    Suemori, Kouji; Kamata, Toshihide

    2012-08-01

    We investigated the effect of dielectric relaxation in polymer gate insulators on the device characteristics of organic field effect transistors. Dielectric relaxation of polymer gate insulators caused an increase in drain current (ID) in a period starting immediately after the application of the gate voltage (VG) and lasting several milliseconds. This induced an apparent delay in the response of ID. Based on the observed results, we suggested an ideal gate insulator to achieve organic field effect transistors that have a fast response and high performance.

  13. Endothelium-dependent vasodilation effects of Panax notoginseng and its main components are mediated by nitric oxide and cyclooxygenase pathways

    PubMed Central

    Wang, Yanyan; Ren, Yu; Xing, Leilei; Dai, Xiangdong; Liu, Sheng; Yu, Bin; Wang, Yi

    2016-01-01

    Panax notoginseng, a traditional Chinese herbal medicine, has been used for the treatment of cardiovascular diseases. The main bioactive components of this species are Panax notoginseng saponins (PNS). The present study aimed to investigate the effects of PNS and five of its main components (ginsenosides Rg1, Re, Rb1 and Rd, and notoginsenoside R1) on rat aorta rings pre-contracted with norepinephrine (NE) and to determine the underlying mechanism of action. Isolated aorta rings (with or without intact endothelium) from adult male Wistar rats were stimulated with NE to induce vasoconstriction, and subsequently treated with different concentrations of PNS and its five main components (Rg1, Re, Rb1, R1 and Rd) separately. This procedure was repeated after pre-incubation with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and the cyclooxygenase (COX) inhibitor indomethacin (INDO), in order to elucidate the mechanism of action of PNS and its components. The results demonstrated that PNS and the components Rg1, Re, Rb1 and R1, but not Rd, induced vessel relaxation in a concentration-dependent manner when the endothelium lining was intact. NO synthase inhibitor L-NAME and guanylate cyclase inhibitor ODQ attenuated the diastolic effects of PNS, Rg1, Re, Rb1 and R1 in aortic rings with intact endothelium. By contrast, INDO, a known COX inhibitor weakened the vasodilation effects of PNS, Re and Rb1 but demonstrated no effect on Rg1 and R1. In conclusion, PNS and two of its main components (Re and Rb1) exert vasodilating effects through the NO and COX pathways. PMID:28101178

  14. The preoperative use of the relaxation response with ambulatory surgery patients.

    PubMed

    Domar, A D; Noe, J M; Benson, H

    1987-01-01

    The efficacy of the regular elicitation of the relaxation response in reducing surgical anxiety and pain in an ambulatory surgery setting was studied in a population of patients scheduled for the surgical removal of a skin cancer. Forty-nine patients with skin cancer were enrolled in the study immediately after being informed of the ned for surgery; 21 of these patients elicited the relaxation response 20 minutes per day until the day of surgery, 21 read for 20 minutes per day, and 7 were noncompliant and were excluded from the study. Contrary to expectations, neither group of patients showed any increase in anxiety immediately before or after surgery on either psychological or physiological measures. Thus, there were no differences between the two groups on any of the psychological or physiological measures of anxiety, nor were there any differences in pain perception. There were statistically significant subjective differences; the experimental patients stated that the relaxation-response technique had reduced their anxiety several days before surgery and reportedly experienced their highest levels of anxiety prior to entering the study, while the controls experienced their highest levels of anxiety during and after surgery. This suggests that (1) minor outpatient surgery does not lead to detectable increased anxiety levels on the day of surgery and (2) regular elicitation of the relaxation response can alter subjective reports of distress associated with surgery.

  15. Integrating a relaxation response-based curriculum into a public high school in Massachusetts.

    PubMed

    Foret, Megan M; Scult, Matthew; Wilcher, Marilyn; Chudnofsky, Rana; Malloy, Laura; Hasheminejad, Nicole; Park, Elyse R

    2012-04-01

    Academic and societal pressures result in U.S. high school students feeling stressed. Stress management and relaxation interventions may help students increase resiliency to stress and overall well-being. The objectives of this study were to examine the feasibility (enrollment, participation and acceptability) and potential effectiveness (changes in perceived stress, anxiety, self-esteem, health-promoting behaviors, and locus of control) of a relaxation response (RR)-based curriculum integrated into the school day for high school students. The curriculum included didactic instruction, relaxation exercises, positive psychology, and cognitive restructuring. The intervention group showed significantly greater improvements in levels of perceived stress, state anxiety, and health-promoting behaviors when compared to the wait list control group. The intervention appeared most useful for girls in the intervention group. The results suggest that several modifications may increase the feasibility of using this potentially effective intervention in high schools.

  16. Dielectric relaxations and dielectric response in multiferroic BiFeO{sub 3} ceramics

    SciTech Connect

    Hunpratub, Sitchai; Thongbai, Prasit; Maensiri, Santi; Yamwong, Teerapon; Yimnirun, Rattikorn

    2009-02-09

    Single-phase multiferroic BiFeO{sub 3} ceramics were fabricated using pure precipitation-prepared BiFeO{sub 3} powder. Dielectric response of BiFeO{sub 3} ceramics was investigated over a wide range of temperature and frequency. Our results reveal that the BiFeO{sub 3} ceramic sintered at 700 deg. C exhibited high dielectric permittivity, and three dielectric relaxations were observed. A Debye-type dielectric relaxation at low temperatures (-50 to 20 deg. C) is attributed to the carrier hopping process between Fe{sup 2+} and Fe{sup 3+}. The other two dielectric relaxations at the temperature ranges 30-130 deg. C and 140-200 deg. C could be due to the grain boundary effect and the defect ordering and/or the conductivity, respectively.

  17. ATP and vasoactive intestinal polypeptide relaxant responses in hamster isolated proximal urethra

    PubMed Central

    Pinna, Christian; Puglisi, Lina; Burnstock, Geoffrey

    1998-01-01

    Nitric oxide (NO) is known from previous studies to be the principle transmitter in NANC inhibitory nerves supplying the hamster urethra. However, the identity of the cotransmitter(s) responsible for the responses remaining following block with L-NG-nitroarginine methyl ester (L-NAME) is not known. Electrical field stimulation (EFS) of circular strips of hamster proximal urethra precontracted with arginine vasopressin (AVP 10−8 M), and in the presence of phentolamine (10−6 M), propranolol (10−6 M) and atropine (10−6 M), caused frequency-dependent relaxation, which was attenuated by suramin (10−4 M) and reactive blue 2 (RB2; 2×10−4 M), but not by pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS; 10−4 M), α-chymotrypsin (10–50 u ml−1) or by the vasoactive intestinal polypeptide (VIP) antagonist, [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP, (5×10−7–10−6 M). In the presence of indomethacin (10−6 M) frequency-dependent relaxations to EFS were enhanced, particularly at the lower frequencies of stimulation. EFS-induced relaxation was blocked by tetrodotoxin (10−6 M), indicating its neurogenic origin. Exogenous ATP (10−7–10−3 M) produced concentration-related relaxations which were attenuated by the P2-purinoceptor antagonists suramin (10−4 M) and RB2 (2×10−4 M) but not by PPADS (10−4 M). ATP-induced relaxations were also reduced significantly by indomethacin (10−6 M). The inhibitory responses to ATP were urothelium- and NO-independent, since they were not affected by either removal of urothelium or by L-NAME (10−4 M). Exogenous VIP (10−9–10−7 M) induced concentration-related relaxations which were not affected by urothelium removal, L-NAME (10−4 M), α-chymotrypsin (10–50 u ml−1) or by [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (3×10−7–10−6 M). Nevertheless, suramin (10−4 M) and RB2 (2×10−4 M) but not PPADS (10−4 M) antagonized the VIP-induced relaxant

  18. Atherosclerosis measured by whole body magnetic resonance angiography and carotid artery ultrasound is related to arterial compliance, but not to endothelium-dependent vasodilation - the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.

    PubMed

    Lind, Lars; Andersson, Jessika; Hansen, Tomas; Johansson, Lars; Ahlström, Håkan

    2009-09-01

    Arterial compliance and endothelium-dependent vasodilation are two characteristics of the vessel wall. In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, we studied the relationships between arterial compliance and endothelium-dependent vasodilation versus atherosclerosis as measured with two imaging modalities. In the population-based PIVUS study (1016 subjects aged 70), arterial compliance was determined by ultrasound in the carotid artery and the stroke volume to pulse pressure ratio by echocardiography, while endothelium-dependent vasodilation was assessed by the invasive forearm technique with acetylcholine and brachial artery ultrasound. Intima-media thickness was evaluated by ultrasound in the carotid artery (n = 954). Stenosis in the carotid, aorta, renal, upper and lower leg arteries were determined by magnetic resonance angiography in a random subsample of 306 subjects. After adjustments for gender, Framingham risk score, obesity, myocardial infarction and stroke, distensibility in the carotid artery and the stroke volume to pulse pressure ratio were both significantly related to a weighted index of stenosis in the five arterial territories evaluated by magnetic resonance angiography (p<0.02 for both). Distensibility in the carotid artery (P = 0.021), but not the stroke volume to pulse pressure ratio (P = 0.08), was also significantly related to intima-media thickness. In the elderly population, atherosclerosis is mainly related to arterial compliance, but not to endothelium-dependent vasodilation in peripheral conduit or resistance vessels.

  19. Endothelium-dependent vasodilation in myogenically active mouse skeletal muscle arterioles: role of EDH and K(+) channels.

    PubMed

    Potocnik, Simon J; McSherry, Iain; Ding, Hong; Murphy, Timothy V; Kotecha, Neela; Dora, Kim A; Yuill, Kathryn H; Triggle, Chris R; Hill, Michael A

    2009-07-01

    As smooth muscle cell (SMC) membrane potential (E(m)) is critical for vascular responsiveness, and arteriolar SMCs are depolarized at physiological intraluminal pressures, we hypothesized that myogenic tone impacts on dilation mediated by endothelium-derived hyperpolarization (EDH). Studies were performed on cannulated mouse cremaster arterioles [diameter, 33+/-2 microm (n=23) at 60 mmHg; SMC Em -34.6+/-1.2 mV (n=7)]. Myogenic activity was assessed as tone developed in response to intraluminal pressure. Functional observations were related to mRNA, protein expression, and anatomy. Acetylcholine concentration-response curves showed a modest shift following indomethacin (10 microM) and L-NAME (100 microM), although maximal vasodilation was achieved. Residual dilation was removed by apamin (1 microM) in combination with TRAM-34 (1 microM) or charybotoxin (0.1 microM), indicating the requirement of small (S) and intermediate (I) calcium-activated potassium channels (K(Ca)). Charybdotoxin, but not TRAM-34, caused vasoconstriction, presumably through the inhibition of SMC BK(Ca). Expression of SK3 and IK1 was confirmed by immunohistochemistry and polymerase chain reaction, while myoendothelial junctions were common, suggesting a high degree of cell coupling. Also consistent with a role for endothelial K(Ca) channels, acetylcholine increased endothelium [Ca(2 +)](i). Apamin and TRAM-34 similarly blocked EDH-mediated dilation at intraluminal pressures of 30 and 90 mmHg, suggesting that in mouse arterioles, SK(Ca -) and IK(Ca -) mediated mechanisms predominate and operate independently of physiological levels of myogenic activation.

  20. Effects of diabetes and evening primrose oil treatment on responses of aorta, corpus cavernosum and mesenteric vasculature in rats.

    PubMed

    Jack, Alison M; Keegan, Alan; Cotter, Mary A; Cameron, Norman E

    2002-09-06

    Diabetes causes endothelial dysfunction, with deleterious effects on nitric oxide (NO) mediated vasodilatation. However, in many vessels other local vasodilators such as endothelium-derived hyperpolarizing factor (EDHF), prostacyclin, epoxides or endocannabinoids are also important. Several of these factors may be derived from omega-6 essential fatty acids via arachidonate metabolism. Diabetes inhibits this pathway, a defect that may be bypassed by diets enriched with omega-6 gamma-linolenic acid-containing oils such as evening primrose oil (EPO). The aim was to examine the effects of preventive EPO treatment on endothelium-dependent and neurally mediated vasorelaxation. Diabetes was induced by streptozotocin in rats; duration was 8 weeks. Vascular responses were examined in vitro on thoracic aorta, corpus cavernosum and perfused mesenteric bed preparations. Diabetes caused 25% and 35% deficits, respectively, in aorta and corpus cavernosum NO-mediated endothelium-dependent relaxation to acetylcholine that were largely unaffected by EPO treatment. Moreover, a 44% reduction in maximum corpus cavernosum vasorelaxation to nitrergic nerve stimulation was not prevented by EPO. However, for the mesenteric vascular bed, a 29% diminution of responses to acetylcholine, mediated by both NO and EDHF, was 84% attenuated by EPO treatment. When the EDHF component was isolated during NO synthase inhibition, a 76% diabetic deficit was noted. This was completely prevented by EPO treatment, which also caused supernormal EDHF responses in nondiabetic rats. EPO treatment prevented the development of deficits in endothelium-dependent relaxation in diabetic rats. Effects were particularly marked on the resistance vessel EDHF system, which may have potential therapeutic relevance for diabetic microvascular complications.

  1. Vasorelaxant responses to endomorphins, nociceptin, albuterol, and adrenomedullin in isolated rat aorta.

    PubMed

    Hugghins, S Y; Champion, H C; Cheng, G; Kadowitz, P J; Jeter, J R

    2000-06-16

    The endogenous peptides endomorphins 1 and 2 are newly discovered, potent, selective mu-opioid receptor agonists. In the present study, the effects of endomorphins 1 and 2 on vascular smooth muscle tone were investigated on isolated rings from rat aorta with and without endothelium. In rings precontracted with phenylephrine, endomorphins 1 and 2 at concentrations of 0.1 and 1.0 microM, nociceptin at concentrations of 1-100 microM, and adrenomedullin at concentrations of 0.01-1.0 microM induced concentration dependent relaxant responses. The endomorphins and nociceptin were less potent than adrenomedullin. No relaxation was induced by endomorphins 1 and 2 in aortic rings denuded of endothelium and precontracted with phenylephrine. The results of the present studies demonstrate that the endomorphins relax aortic vascular smooth muscle from the rat aorta by an endothelium-dependant mechanism.

  2. AKAP150-dependent cooperative TRPV4 channel gating is central to endothelium-dependent vasodilation and is disrupted in hypertension

    PubMed Central

    Sonkusare, Swapnil K.; Dalsgaard, Thomas; Bonev, Adrian D.; Hill-Eubanks, David C.; Kotlikoff, Michael I.; Scott, John D.; Santana, Luis F.; Nelson, Mark T.

    2015-01-01

    Endothelial cell dysfunction, characterized by a diminished response to endothelial cell–dependent vasodilators, is a hallmark of hypertension. TRPV4 channels play a major role in endothelial-dependent vaso-dilation, a function mediated by local Ca2+ influx through clusters of functionally coupled TRPV4 channels rather than by a global increase in endothelial cell Ca2+. We showed that stimulation of muscarinic acetylcholine receptors on endothelial cells of mouse arteries exclusively activated TRPV4 channels that were localized at myoendothelial projections (MEPs), specialized regions of endothelial cells that contact smooth muscle cells. Muscarinic receptor–mediated activation of TRPV4 depended on protein kinase C (PKC) and the PKC-anchoring protein AKAP150, which was concentrated at MEPs. Cooperative opening of clustered TRPV4 channels specifically amplified Ca2+ influx at MEPs. Cooperativity of TRPV4 channels at non-MEP sites was much lower, and cooperativity at MEPs was greatly reduced by chelation of intracellular Ca2+ or AKAP150 knockout, suggesting that Ca2+ entering through adjacent channels underlies the AKAP150-dependent potentiation of TRPV4 activity. In a mouse model of angiotensin II–induced hypertension, MEP localization of AKAP150 was disrupted, muscarinic receptor stimulation did not activate TRPV4 channels, cooperativity among TRPV4 channels at MEPs was weaker, and vasodilation in response to muscarinic receptor stimulation was reduced. Thus, endothelial-dependent dilation of resistance arteries is enabled by MEP-localized AKAP150, which ensures the proximity of PKC to TRPV4 channels and the coupled channel gating necessary for efficient communication from endothelial to smooth muscle cells in arteries. Disruption of this molecular assembly may contribute to altered blood flow in hypertension. PMID:25005230

  3. The origin of the Debye relaxation in liquid water and fitting the high frequency excess response.

    PubMed

    Elton, Daniel C

    2017-07-19

    We critically review the literature on the Debye absorption peak of liquid water and the excess response found on the high frequency side of the Debye peak. We find a lack of agreement on the microscopic phenomena underlying both of these features. To better understand the molecular origin of Debye peak we ran large scale molecular dynamics simulations and performed several different distance-dependent decompositions of the low frequency dielectric spectra, finding that it involves processes that take place on scales of 1.5-2.0 nm. We also calculated the k-dependence of the Debye relaxation, finding it to be highly dispersive. These findings are inconsistent with models that relate Debye relaxation to local processes such as the rotation/translation of molecules after H-bond breaking. We introduce the spectrumfitter Python package for fitting dielectric spectra and analyze different ways of fitting the high frequency excess, such as including one or two additional Debye peaks. We propose using the generalized Lydanne-Sachs-Teller (gLST) equation as a way of testing the physicality of model dielectric functions. Our attempts at fitting the experimental spectrum using the gLST relation as a constraint indicate that the traditional way of fitting the excess response with secondary and tertiary Debye relaxations is problematic. All of our work is consistent with the recent theory of Popov et al. (2016) that Debye relaxation is due to the migration of Bjerrum-like defects in the hydrogen bond network. Under this theory, the mechanism of Debye relaxation in liquid water is similar to the mechanism in ice, but the heterogeneity and power-law dynamics of the H-bond network in water results in excess response on the high frequency side of the peak.

  4. Sex differences in angiotensin II responses contribute to a differential regulation of cox-mediated vascular dysfunction during aging.

    PubMed

    Costa, Gustavo; Garabito, Manel; Jiménez-Altayó, Francesc; Onetti, Yara; Sabate, Manel; Vila, Elisabet; Dantas, Ana Paula

    2016-12-01

    Aging is a cardiovascular risk factor partially related to activation of the Renin-Angiotensin System (RAS). RAS activation is also influenced by sex. In this regard, our study aims to determine whether sex-associated differences in RAS contribute to a differential regulation of vascular aging and associated dysfunction. Male and female outbreed CD-1 mice were studied at 3 and 12months of age (M). Contribution of RAS was determined by treating mice from 3M to 12M with the AngII type 1 receptor blocker losartan (0.6g/L in the drinking water). At 12M, contractions to AngII were higher in males compared to females (P<0.05). This effect was paralleled by a decrease in AngII type 2 receptors in 12M males. Aging also diminished ACh relaxation in males, but did not modify female responses. Treatment of aortas with indomethacin (10μM) restored the impaired endothelium-dependent relaxation in 12M males, suggesting an increase of cyclooxygenase (COX)-derived vasoconstrictors in aged males. Chronic treatment of mice with losartan also improved endothelium-dependent relaxation. Besides, losartan significantly decreased COX-2 expression and activity in 12M male, with a minor effect in aged females. Aging increases AngII contraction and induces endothelial dysfunction differently in males and females. In aged males, RAS contributed to increased COX-2 expression and activity, which in turn may lead to vascular dysfunction.

  5. Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect.

    PubMed

    Celotto, A C; Ferreira, L G; Capellini, V K; Albuquerque, A A S; Rodrigues, A J; Evora, P R B

    2016-02-01

    Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.

  6. Association of cytokines with endothelium dependent flow mediated vasodilation (FMD) of systemic arteries in patients with non-ischemic cardiomyopathy.

    PubMed

    Vallbracht-Israng, Katja B; Kazak, Ilkay; Schwimmbeck, Peter L

    2007-12-10

    Aim of this study was to elucidate the relation between localised inflammatory heart disease and endothelial dysfunction in the peripheral circulation, considering circulating cytokines as a potential link. In 38 patients with non-ischemic heart disease, myocardial biopsies were examined for myocardial inflammation (immunohistology) and virus persistence (PCR). Cytokines (sIL-4, IFN-g, IFN-b, IFN-a, sIL-12p7, TNF-a) were measured by ELISA in venous serum. Endothelial function of the radial artery was examined by ultrasound, measuring diameter changes in response to reactive hyperemia (FMD), compared to glyceroltrinitrate (GTN-MD). Patients with EF < 35% were excluded. Age 44 +/- 14 years, 19 male, 19 female, EF 63.5[16]%. FMD 4.38 [4.82]%. 30 patients had myocardial inflammation (8 not), 23 virus persistence (15 not). FMD correlated significantly with sIL-12p7 (p = 0.024, r = -0.365), but not with other cytokines. sIL-12p7 levels were significantly higher in patients with severely impaired FMD (n = 17), compared with normal FMD (n = 21): 10.70 [10.72] vs. 4.33 [7.81] pg/ml (p = 0.002). Endothelium independent vasodilation (GTN-MD 23.67 [8.21]%) was not impaired. Endothelial dysfunction of peripheral arteries in patients with non-ischemic cardiomyopathy is associated with elevated serum concentrations of sIL-12p7, but not of other cytokines. Circulating sIL-12p7 may partly explain, that endothelial dysfunction is not restricted to the coronary circulation, but involves systemic arteries.

  7. Exercise training-enhanced, endothelium-dependent dilation mediated by altered regulation of BKCa channels in collateral-dependent porcine coronary arterioles

    PubMed Central

    Xie, Wei; Parker, Janet L.; Heaps, Cristine L.

    2012-01-01

    Objective Test the hypothesis that exercise training increases the contribution of large-conductance, Ca2+-dependent K+ (BKCa) channels to endothelium-mediated dilation in coronary arterioles from collateral-dependent myocardial regions of chronically occluded pig hearts and may function downstream of H2O2. Methods An ameroid constrictor was placed around the proximal left circumflex coronary artery to induce gradual occlusion in Yucatan miniature swine. Eight weeks postoperatively, pigs were randomly assigned to sedentary or exercise training (treadmill; 14 wk) regimens. Results Exercise training significantly enhanced bradykinin-mediated dilation in collateral-dependent arterioles (~125 μm diameter) compared with sedentary pigs. The BKCa-channel blocker, iberiotoxin alone or in combination with the H2O2 scavenger, polyethylene glycol catalase, reversed exercise training-enhanced dilation in collateral-dependent arterioles. Iberiotoxin-sensitive whole-cell K+ currents (i.e., BKCa-channel currents) were not different between smooth muscle cells of nonoccluded and collateral-dependent arterioles of sedentary and exercise trained groups. Conclusions These data provide evidence that BKCa-channel activity contributes to exercise training-enhanced endothelium-dependent dilation in collateral-dependent coronary arterioles despite no change in smooth muscle BKCa-channel current. Taken together, our findings suggest that a component of the bradykinin signaling pathway, which stimulates BKCa channels, is enhanced by exercise training in collateral-dependent arterioles and suggest a potential role for H2O2 as the mediator. PMID:23002811

  8. Resveratrol induces acute endothelium-dependent renal vasodilation mediated through nitric oxide and reactive oxygen species scavenging

    PubMed Central

    Gordish, Kevin L.

    2014-01-01

    Resveratrol is suggested to have beneficial cardiovascular and renoprotective effects. Resveratrol increases endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. We hypothesized resveratrol acts as an acute renal vasodilator, mediated through increased NO production and scavenging of reactive oxygen species (ROS). In anesthetized rats, we found 5.0 mg/kg body weight (bw) of resveratrol increased renal blood flow (RBF) by 8% [from 6.98 ± 0.42 to 7.54 ± 0.17 ml·min−1·gram of kidney weight−1 (gkw); n = 8; P < 0.002] and decreased renal vascular resistance (RVR) by 18% from 15.00 ± 1.65 to 12.32 ± 1.20 arbitrary resistance units (ARU; P < 0.002). To test the participation of NO, we administered 5.0 mg/kg bw resveratrol before and after 10 mg/kg bw of the NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME). l-NAME reduced the increase in RBF to resveratrol by 54% (from 0.59 ± 0.05 to 0.27 ± 0.06 ml·min−1·gkw−1; n = 10; P < 0.001). To test the participation of ROS, we gave 5.0 mg/kg bw resveratrol before and after 1 mg/kg bw tempol, a superoxide dismutase mimetic. Resveratrol increased RBF 7.6% (from 5.91 ± 0.32 to 6.36 ± 0.12 ml·min−1·gkw−1; n = 7; P < 0.001) and decreased RVR 19% (from 18.83 ± 1.37 to 15.27 ± 1.37 ARU). Tempol blocked resveratrol-induced increase in RBF (from 0.45 ± 0.12 to 0.10 ± 0.05 ml·min−1·gkw−1; n = 7; P < 0.03) and the decrease in RVR posttempol was 44% of the control response (3.56 ± 0.34 vs. 1.57 ± 0.21 ARU; n = 7; P < 0.006). We also tested the role of endothelium-derived prostanoids. Two days of 10 mg/kg bw indomethacin pretreatment did not alter basal blood pressure or RBF. Resveratrol-induced vasodilation remained unaffected. We conclude intravenous resveratrol acts as an acute renal vasodilator, partially mediated by increased NO production/NO bioavailability and superoxide scavenging but not by inducing vasodilatory cyclooxygenase products. PMID:24431202

  9. Age-related changes to vascular protease-activated receptor 2 in metabolic syndrome: a relationship between oxidative stress, receptor expression, and endothelium-dependent vasodilation.

    PubMed

    Maruyama, Kana; Kagota, Satomi; McGuire, John J; Wakuda, Hirokazu; Yoshikawa, Noriko; Nakamura, Kazuki; Shinozuka, Kazumasa

    2017-04-01

    Protease-activated receptor 2 (PAR2) is expressed in vascular endothelium. Nitric oxide (NO) - cyclic GMP-mediated vasodilation in response to 2-furoyl-LIGRLO-amide (2fLIGRLO), a PAR2-activating peptide, is impaired in aortas from aged SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP.ZF) rats with metabolic syndrome. Here we investigated mechanisms linking PAR2's vascular effects to phenotypic characteristics of male SHRSP.ZF rats at 10, 20, and 30 weeks of age. We found vasodilation responses to either 2fLIGRLO or enzyme-mediated PAR2 activation by trypsin were sustained until 20 weeks and lessened at 30 weeks. PAR2 protein and mRNA levels were lower in aortas at 30 weeks than at 10 and 20 weeks. PAR2-mediated responses positively correlated with PAR2 protein and mRNA levels. Decreased cGMP accumulation in the presence of 2fLIGRLO paralleled the decreased relaxations elicited by nitroprusside and the cGMP analog 8-pCPT-cGMP, and the less soluble guanylyl cyclase protein at 30 weeks. 2fLIGRLO-induced relaxation was negatively correlated with serum thiobarbituric acid reactive substances, an index of oxidative stress, which increased with age. Forward stepwise data regression supported a model of age-related decreases in PAR2 function resulting from decreased PAR2 mRNA and increased oxidative stress. We conclude that decreased responsiveness of aortic smooth muscle to NO and downregulation of receptor expression impair PAR2 functions at later stages of metabolic syndrome in SHRSP.ZF rats.

  10. Airflow and autonomic responses to stress and relaxation in asthma: the impact of stressor type.

    PubMed

    Aboussafy, David; Campbell, Tavis S; Lavoie, Kim; Aboud, Frances E; Ditto, Blaine

    2005-09-01

    The impact of stress on respiratory airflow in asthmatics is unclear. Part of the uncertainty may spring from the different physiological effects of different stressors. Given their potential to elicit increases in parasympathetic vagal activity, stressful situations that present few opportunities for coping (passive coping stressors) may be particularly problematic for people with asthma. Thirty-one adult asthmatics participated in a protocol including a widely used passive coping stressor (the cold pressor test), an active coping stressor (mental arithmetic), an interview about an upsetting asthma-related incident (viewed as a potential passive coping stressor given the exposure to unpleasant memories), and progressive muscle relaxation. Repeated measurements of airflow (via peak expiratory flow), vagal tone (via heart rate variability), and other variables were obtained. The cold pressor test, asthma interview and progressive muscle relaxation produced significant decreases in airflow compared to the baseline period. The cold pressor test and progressive muscle relaxation produced significant, complementary increases in vagal tone. These results suggest that passive coping stressors and other stimuli (e.g., certain forms of relaxation) that elicit increased vagal tone may be associated with poorer asthma control, a view consistent with a significant negative correlation between the participant's mean vagal tone response to the tasks and score on a measure of asthma self-efficacy.

  11. A unique dysprosium selenoarsenate(iii) exhibiting a photocurrent response and slow magnetic relaxation behavior.

    PubMed

    Zhou, Jian; Zou, Hua-Hong; Zhao, Rongqing; Xiao, Hong; Ding, Qingran

    2017-01-03

    A redox, substitution and self-assembly reaction offers a novel dysprosium selenoarsenate(iii) with As(3+) [Dy2(tepa)2(μ2-OH)2Cl2]3[As3Se6]2 (1, tepa = tetraethylenepentamine), which provides the first example of chair conformation ring [As3Se6](3-) combined with lanthanide complexes as counterions. 1 exhibits a photocurrent response and slow magnetic relaxation behavior.

  12. Highly nonlinear stress-relaxation response of articular cartilage in indentation: Importance of collagen nonlinearity.

    PubMed

    Mäkelä, J T A; Korhonen, R K

    2016-06-14

    Modern fibril-reinforced computational models of articular cartilage can include inhomogeneous tissue composition and structure, and nonlinear mechanical behavior of collagen, proteoglycans and fluid. These models can capture well experimental single step creep and stress-relaxation tests or measurements under small strains in unconfined and confined compression. Yet, it is known that in indentation, especially at high strain velocities, cartilage can express highly nonlinear response. Different fibril reinforced poroelastic and poroviscoelastic models were used to assess measured highly nonlinear stress-relaxation response of rabbit articular cartilage in indentation. Experimentally measured depth-dependent volume fractions of different tissue constituents and their mechanical nonlinearities were taken into account in the models. In particular, the collagen fibril network was modeled using eight separate models that implemented five different constitutive equations to describe the nonlinearity. These consisted of linear elastic, nonlinear viscoelastic and multiple nonlinear elastic representations. The model incorporating the most nonlinearly increasing Young׳s modulus of collagen fibrils as a function of strain captured best the experimental data. Relative difference between the model and experiment was ~3%. Surprisingly, the difference in the peak forces between the experiment and the model with viscoelastic collagen fibrils was almost 20%. Implementation of the measured volume fractions did not improve the ability of the model to capture the measured mechanical data. These results suggest that a highly nonlinear formulation for collagen fibrils is needed to replicate multi-step stress-relaxation response of rabbit articular cartilage in indentation with high strain rates.

  13. Cervical flexion-relaxation response to neck muscle fatigue in males and females.

    PubMed

    Nimbarte, Ashish D; Zreiqat, Majed M; Chowdhury, Suman Kanti

    2014-12-01

    In this study the effect of muscle fatigue on the cervical spine flexion-relaxation response was studied. Twenty healthy participants (10 males and 10 females) were recruited for data collection. The Sorenson protocol was utilized to induce neck muscle fatigue. Surface electromyography and optical motion capture systems were used to measure neck muscle activation and head-neck posture, respectively. A post-fatigue reduction in the Flexion-Relaxation Ratio (FRR) and higher FRR for females compared to males were observed. A post-fatigue decrease was also observed in the onset and offset angles resulting in an expansion of the myoelectric silence period. Gender had no effect on the onset and offset angles of the silence period. Post-fatigue shift in the onset and offset angles and the expansion of the silence period indicate an increased contribution by the passive viscoelastic tissues in stabilizing the cervical spine under fatigued condition.

  14. Effects of endopeptidase inhibition on the contraction-relaxation response of isolated human vaginal tissue.

    PubMed

    Rahardjo, Harrina E; Uckert, Stefan; Taher, Akmal; Sonnenberg, Joachim E; Kauffels, Wolfgang; Rahardjo, Djoko; Kuczyk, Markus A

    2013-04-01

    INTRODUCTION.: Vasoactive peptides, such as bradykinin, C-type natriuretic peptide (CNP), vasoactive intestinal polypeptide (VIP), and endothelin 1 (ET-1), are assumed to be involved in the control of female genital vascular and nonvascular smooth muscle. Tissue levels of said peptides are controlled by the activity of endopeptidase enzymes. Theoretically, in female genital tissues, inhibiting the degradation of bradykinin, CNP, and VIP, or the conversion of Big ET-1 into ET-1 should result in an enhancement in smooth muscle relaxation and, thus, an improvement in sexual response. AIM.: Elucidate the effects of the endopeptidase inhibitor KC 12615 on the contraction/relaxation response of isolated human vaginal smooth muscle to Big ET-1, bradykinin, CNP, or VIP. METHODS.: Tissue bath experiments were carried out to ascertain the responses of human vaginal tissue challenged by ET-1 (0.1 μM) to increasing concentrations of bradykinin, CNP, and VIP (0.01 μM, 0.1 μM, and 1 μM, respectively). The effects were also evaluated following preexposure to KC 12615 (10 μM, for 20 minutes). MAIN OUTCOME MEASURES.: Measure the effects of KC 12615 on the relaxation of isolated human vaginal smooth muscle brought about by bradykinin, CNP, or VIP and the contraction mediated by Big ET-1. RESULTS.: The tension induced by ET-1 was reversed by bradykinin, CNP, or VIP (-25 ± 6.6%, -13.3 ± 2.2%, and -17.6 ± 10%, respectively). Big ET-1 induced contraction of the vaginal tissue. Preexposure of the tissue to KC 12615 increased the relaxation exerted by bradykinin, CNP, or VIP (to -39.2 ± 5.8%, -40.7 ± 7.3%, and -44.6 ± 19%, respectively). The contraction induced by Big ET-1 was attenuated in the presence of KC 12615 (to approximately 25% of the initial response). CONCLUSION.: Inhibition of endopeptidase activity can antagonize the contraction of human vaginal tissue induced by Big ET-1 and increase the relaxation induced by vasoactive endogenous

  15. A factorial randomized controlled trial to evaluate the effect of micronutrients supplementation and regular aerobic exercise on maternal endothelium-dependent vasodilatation and oxidative stress of the newborn

    PubMed Central

    2011-01-01

    Background Many studies have suggested a relationship between metabolic abnormalities and impaired fetal growth with the development of non-transmissible chronic diseases in the adulthood. Moreover, it has been proposed that maternal factors such as endothelial function and oxidative stress are key mechanisms of both fetal metabolic alterations and subsequent development of non-transmissible chronic diseases. The objective of this project is to evaluate the effect of micronutrient supplementation and regular aerobic exercise on endothelium-dependent vasodilation maternal and stress oxidative of the newborn. Methods and design 320 pregnant women attending to usual prenatal care in Cali, Colombia will be included in a factorial randomized controlled trial. Women will be assigned to the following intervention groups: 1. Control group: usual prenatal care (PC) and placebo (maltodextrine). 2. Exercise group: PC, placebo and aerobic physical exercise. 3. Micronutrients group: PC and a micronutrients capsule consisting of zinc (30 mg), selenium (70 μg), vitamin A (400 μg), alphatocopherol (30 mg), vitamin C (200 mg), and niacin (100 mg). 4. Combined interventions Group: PC, supplementation of micronutrients, and aerobic physical exercise. Anthropometric measures will be taken at the start and at the end of the interventions. Discussion Since in previous studies has been showed that the maternal endothelial function and oxidative stress are related to oxidative stress of the newborn, this study proposes that complementation with micronutrients during pregnancy and/or regular physical exercise can be an early and innovative alternative to strengthen the prevention of chronic diseases in the population. Trial registration NCT00872365. PMID:21356082

  16. Hydroalcoholic extract and pure compounds from Senecio nutans Sch. Bip (Compositae) induce vasodilation in rat aorta through endothelium-dependent and independent mechanisms.

    PubMed

    Paredes, Adrián; Palacios, Javier; Quispe, Cristina; Nwokocha, Chukwuemeka R; Morales, Glauco; Kuzmicic, Jovan; Cifuentes, Fredi

    2016-11-04

    Senecio nutans Sch. Bip. (Compositae) is an endemic plant of South America, and is used in herbal medicine in Andean communities for treating acute mountain sickness. Currently, the direct effects of hydroalcoholic extract of S. nutans (HAE S. nutans) or its isolated compounds on the vascular system are not well described. The aim of this study was to determine the effects and mechanism of action of S. nutans on vascular function in healthy rats. Seven compounds were isolated from the HAE S. nutans, and their structures were characterized using spectroscopic techniques as 1D and 2D NMR, and mass spectrometry. Vascular reactivity experiments were carried out in rat aorta. S. nutans-dependent vasodilation and phenylephrine-dependent contraction were measured in endothelium-intact and endothelium-denuded aortic rings of male rats. Seven pure compounds were isolate from HAE S. nutans, but two pure compounds showed significant vasodilation in rat aorta: 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone (compound E) and 5-acetyl-6-hydroxy-2-isopropenyl-2,3-dihydrobenzofurane (compound G). Although HAE S. nutans induced vasodilation in absence of endothelium, the vasodilation in intact aorta, via NO, was higher. HAE S. nutans reduced calcium-dependent contraction in endothelium-intact, but not in endothelium-denuded aortic rings. HAE S. nutans and its isolated compounds caused vasodilation in rat aorta in absence of endothelium, suggesting its vasodilator properties is endothelium-dependent (NO) and or independent, and may involve a modulation of the calcium channels. This result is of clinical interest as potential therapy control of blood pressure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Relation of Season and Temperature to Endothelium-Dependent Flow-Mediated Vasodilation in Subjects Without Clinical Evidence of Cardiovascular Disease (From The Framingham Heart Study)

    PubMed Central

    Widlansky, Michael E.; Vita, Joseph A.; Keyes, Michelle J.; Larson, Martin G.; Hamburg, Naomi M.; Levy, Daniel; Mitchell, Gary F.; Osypiuk, Ewa W.; Vasan, Ramachandran S.; Benjamin, Emelia J.

    2007-01-01

    Multiple studies have documented an increased incidence of cardiovascular events in the winter, but the pathophysiological mechanisms remain incompletely understood. We hypothesized that brachial flow and flow-mediated dilation (FMD) would vary by season and temperature. We related season and temperature to ultrasonic brachial artery endothelium-dependent FMD% (n=2587), baseline flow velocity and maximal reactive hyperemia (n=1973) in the Framingham Offspring cohort (mean age 61±10 years; 53% women). We obtained outdoor temperature from National Climate Data Center records for Bedford, Massachusetts (about 14 miles from testing site) and we measured the examination room temperature. In multivariable models, FMD% was highest in summer and lowest in winter (3.01±0.09 vs. 2.56±0.10%, respectively; P=0.02 for differences across all 4 seasons). FMD% was highest in the warmest and lowest in the coldest outdoor temperature quartiles. In stepwise models adjusting for risk factors, and selecting among season, outdoor temperature, and room temperature, FMD% was associated with season (P=0.02); temperature did not enter the model. In contrast, hyperemic flow velocity was significantly lower for cooler, and higher for warmer room temperatures (P=0.02 overall); season did not enter the model. Season, outdoor and room temperature were each retained in a stepwise model of baseline flow velocity (P<0.0001, P=0.02, P<0.0001, respectively). In conclusion, we observed a significant association between season and FMD. Microvascular vasodilator function, as reflected by hyperemic flow, was more strongly related to temperature than season. In conclusion, we speculate that endothelial dysfunction may be 1 of the mechanisms influencing seasonal variation in cardiovascular events. PMID:17659939

  18. Influence of asymmetry on the flexion relaxation response of the low back musculature.

    PubMed

    Ning, Xiaopeng; Haddad, Omid; Jin, Sangeun; Mirka, Gary A

    2011-01-01

    the flexion relaxation phenomenon has been extensively studied in sagittally symmetric postures. Knowledge about this phenomenon in asymmetric trunk postures is less well understood, and may help to reveal the underlying physiology of the passive tissue/active tissue load-sharing mechanism in the lumbar region. twelve participants performed fifteen controlled, full range trunk flexion-extension motions toward three asymmetric lifting postures (0° (sagittally symmetric), 15°, and 30° from the mid-sagittal plane). The electromyographic activity data from the paraspinals at the L3 and L4 levels and trunk kinematics data from motion sensors over the C7, T12 and S1 vertebrae were recorded. The lumbar flexion angles at which these muscles' activities were reduced to resting levels during forward flexion provided quantitative data describing the effects of asymmetry on the passive tissue/active tissue interaction. flexion relaxation was observed in the muscles contralateral to the direction of the asymmetric trunk flexion motion. The response of the ipsilateral extensor musculature was much less consistent, with many trials indicating that flexion relaxation was never achieved. Increasing asymmetry from 0° to 30° led to a 10% reduction in the maximum lumbar flexion. Lumbar flexion angles necessary to achieve flexion relaxation in the contralateral muscles also decreased (L4 paraspinal-related angle decreasing by 15% and the L3 paraspinal-related angle decreasing by 21%). under asymmetric conditions the lumbar flexion angle at which the transition from active muscle to passive ligamentous extension moment is altered from that seen in symmetric motions and this transition can have implications for the loading of the spine in full flexion (or near full flexion) postures. 2010 Elsevier Ltd. All rights reserved.

  19. Relaxant activity of methanolic extract from seeds of Peganum harmala on isolated rat aorta.

    PubMed

    Berrougui, H; Herrera-Gonzalez, M D; Marhuenda, E; Ettaib, A; Hmamouchi, M

    2002-01-01

    The activity of methanolic extract from the seeds of Peganum harmala L. (MEP) on vascular smooth muscle (rat aorta) was investigated. MEP induced relaxation in aorta precontracted with noradrenaline (10(-6) M) or KCl (80 mM) (IC50 = 14.49 +/- 1.15 and 5.93 +/- 1.26 micrograms/mL, respectively) in a dose-dependent manner and this relaxant effect was not endothelium-dependent. The vasodilatory effects were potentiated by isoprenaline (10(-9) M) (1.08 +/- 0.14 micrograms/mL) and negatively affected by a non-specific inhibitor of phosphodiesterase, IBMX (10(-4) M) (20.81 +/- 1.06 micrograms/mL). Pretreatment with MEP (3, 6, 18 micrograms/ml) shifted the phenylephrine-induced dose-response curves to the right and the maximum response was attenuated, indicating that the antagonist effect of MEP on alpha 1-adrenoceptors was non-competitive. These results suggest that MEP exerts a vasodilatory effect not related to the presence of endothelium and the main mechanism may be related to the inhibition of cyclic AMP phosphodiesterase.

  20. Flat-response spin-exchange relaxation free atomic magnetometer under negative feedback.

    PubMed

    Lee, Hyun Joon; Shim, Jeong Hyun; Moon, Han Seb; Kim, Kiwoong

    2014-08-25

    We demonstrate that the use of negative feedback extends the detection bandwidth of an atomic magnetometer in a spin-exchange relaxation free (SERF) regime. A flat-frequency response from zero to 190 Hz was achieved, which is nearly a three-fold enhancement while maintaining sensitivity, 3 fT/Hz1/2 at 100 Hz. With the extension of the bandwidth, the linear correlation between measured signals and a magne-tocardiographic field synthesized for comparison was increased from 0.21 to 0.74. This result supports the feasibility of measuring weak biomagnetic signals containing multiple frequency components using a SERF atomic magnetometer under negative feedback.

  1. Effect of organo-clay on the dielectric relaxation response of silicone rubber

    NASA Astrophysics Data System (ADS)

    Gharavi, N.; Razzaghi-Kashani, M.; Golshan-Ebrahimi, N.

    2010-02-01

    Dielectric elastomers are light weight, low-cost, highly deformable and fast response smart materials capable of converting electrical energy into mechanical work or vice versa. Silicone rubber is a well-known dielectric elastomer which is used as actuator, and in order to enhance the efficiency of this smart material, compounding of silicone rubber with various fillers can be carried out. The effect of organically modified montmorillonite (OMMT) nano-clay on improvement of dielectric properties, actuation stress and its relaxation response was considered in this study. OMMT was dispersed in room temperature vulcanized (RTV) silicone rubber, and a composite film was cast. Using an in-house actuation set-up, it was shown that the actuation stress for a given electric field intensity is higher for composites than that for pristine silicone rubber. Also, the time-dependent actuation response of the samples was evaluated, and it was shown that the characteristic relaxation time of the actuation stress for composites is less than for the pristine rubber as a result of OMMT addition.

  2. Cyclooxygenase-2 Inhibition Restored Endothelium-Mediated Relaxation in Old Obese Zucker Rat Mesenteric Arteries

    PubMed Central

    Vessières, Emilie; Belin de Chantemèle, Eric J.; Toutain, Bertrand; Guihot, Anne-Laure; Jardel, Alain; Loufrani, Laurent; Henrion, Daniel

    2010-01-01

    Metabolic syndrome is associated with reduced endothelial vasodilator function. It is also associated with the induction of cyclooxygenase-2 (COX2), which produces vasoactive prostanoids. The frequency of metabolic syndrome increases with age and aging per se is a risk factor associated with reduced endothelium-mediated relaxation. Nevertheless, the combined effect of aging and metabolic syndrome on the endothelium is less known. We hypothesized that COX2 derived prostanoids may affect endothelium function in metabolic syndrome associated with aging. We used obese Zucker rats, a model of metabolic syndrome. First order mesenteric arteries were isolated from 4- and 12-month-old rats and acetylcholine (endothelium)-dependent relaxation determined using wire-myography. Endothelium-mediated relaxation, impaired in young Zucker rats (89 versus 77% maximal relaxation; lean versus Zucker), was further reduced in old Zucker rats (72 versus 51%, lean versus Zucker). The effect of the nitric oxide-synthesis inhibitor L-NAME on the relaxation was reduced in both young and old Zucker rats without change in eNOS expression level. COX inhibition (indomethacin) improved acetylcholine-mediated relaxation in old obese rats only, suggesting involvement of vasoconstrictor prostanoids. In addition, COX2 inhibition (NS398) and TxA2/PGH2 receptor blockade (SQ29548) both improved relaxation in old Zucker rat arteries. Old Zucker rats had the highest TxB2 (TxA2 metabolite) blood level associated with increased COX2 immunostaining. Chronic COX2 blockade (Celecoxib, 3 weeks) restored endothelium-dependent relaxation in old Zucker rats to the level observed in old lean rats. Thus the combination of aging and metabolic syndrome further impairs endothelium-dependent relaxation by inducing an excessive production of COX2-derived vasoconstrictor(s); possibly TxA2. PMID:21423385

  3. Cyclooxygenase-2 inhibition restored endothelium-mediated relaxation in old obese zucker rat mesenteric arteries.

    PubMed

    Vessières, Emilie; Belin de Chantemèle, Eric J; Toutain, Bertrand; Guihot, Anne-Laure; Jardel, Alain; Loufrani, Laurent; Henrion, Daniel

    2010-01-01

    Metabolic syndrome is associated with reduced endothelial vasodilator function. It is also associated with the induction of cyclooxygenase-2 (COX2), which produces vasoactive prostanoids. The frequency of metabolic syndrome increases with age and aging per se is a risk factor associated with reduced endothelium-mediated relaxation. Nevertheless, the combined effect of aging and metabolic syndrome on the endothelium is less known. We hypothesized that COX2 derived prostanoids may affect endothelium function in metabolic syndrome associated with aging. We used obese Zucker rats, a model of metabolic syndrome. First order mesenteric arteries were isolated from 4- and 12-month-old rats and acetylcholine (endothelium)-dependent relaxation determined using wire-myography. Endothelium-mediated relaxation, impaired in young Zucker rats (89 versus 77% maximal relaxation; lean versus Zucker), was further reduced in old Zucker rats (72 versus 51%, lean versus Zucker). The effect of the nitric oxide-synthesis inhibitor L-NAME on the relaxation was reduced in both young and old Zucker rats without change in eNOS expression level. COX inhibition (indomethacin) improved acetylcholine-mediated relaxation in old obese rats only, suggesting involvement of vasoconstrictor prostanoids. In addition, COX2 inhibition (NS398) and TxA2/PGH2 receptor blockade (SQ29548) both improved relaxation in old Zucker rat arteries. Old Zucker rats had the highest TxB2 (TxA2 metabolite) blood level associated with increased COX2 immunostaining. Chronic COX2 blockade (Celecoxib, 3 weeks) restored endothelium-dependent relaxation in old Zucker rats to the level observed in old lean rats. Thus the combination of aging and metabolic syndrome further impairs endothelium-dependent relaxation by inducing an excessive production of COX2-derived vasoconstrictor(s); possibly TxA2.

  4. Association of the Glu504Lys polymorphism in the aldehyde dehydrogenase 2 gene with endothelium-dependent dilation disorder in Chinese Han patients with essential hypertension.

    PubMed

    Ma, X; Zheng, S; Shu, Y; Wang, Y; Chen, X

    2016-05-01

    In essential hypertension (EH), 30-50% of the variability in blood pressure is determined by genetic factors. The aldehyde dehydrogenase 2 (ALDH2) gene Glu504Lys polymorphism is associated with 'alcohol flush' and might be associated with EH. The aim of the present study was to investigate the association of the Glu504Lys polymorphism in the ALDH2 gene with endothelium-dependent dilation (EDD) disorder in Chinese Han patients with EH. This case-control study enrolled 1210 patients with EH. The control group consisted of 1089 healthy subjects with normal blood pressure. Patients with EH were divided into normal brachial arterial flow-mediated dilation (FMD) (EH1 group, n = 354) versus endothelial dysfunction (EH2 group, n = 856). ALDH2 gene Glu504Lys polymorphism was detected using a DNA microarray. The ALDH2 AA/AG genotypes and the A allele frequencies were significantly higher in the EH group compared with healthy controls (both P < 0.05) and significantly higher in the EH2 group compared with the EH1 group (79.8 vs 51.4%; 45.0 vs 29.1%, respectively; both P < 0.05). Multivariate logistic regression analyses showed that the ALDH2 gene Glu504Lys polymorphism was independently associated with EH (dominant: odds ratio (OR) = 1.38; 95% confidence interval (95% CI) = 1.14-2.82; P = 0.01; additive: OR = 1.32; 95% CI = 1.12-2.44; P = 0.02) as well as with EDD in patients with EH (dominant: OR = 1.49, 95% CI = 1.16-3.01, P = 0.02; additive: OR = 1.43, 95% CI = 1.10-2.87, P = 0.03). The ALDH2 Glu504Lys polymorphism was associated with EDD disorders in Chinese Han patients with EH, providing further evidence that this mutation and 'alcohol flush' are not harmless in this Asian population. © 2016 Royal Australasian College of Physicians.

  5. Association of apolipoprotein-CIII (apoC-III), endothelium-dependent vasodilation and peripheral neuropathy in a multi-ethnic population with type 2 diabetes.

    PubMed

    Pek, Sharon Li Ting; Sum, Chee Fang; Yeoh, Lee Ying; Lee, Simon Biing Ming; Tang, Wern Ee; Lim, Su Chi; Tavintharan, Subramaniam

    2017-07-01

    Diabetic peripheral neuropathy (DPN) is a common complication of Type 2 diabetes (T2D). Apart from hyperglycemia, its pathogenesis is poorly understood. Apolipoprotein-CIII (apoC-III) associated with triglyceride metabolism, is a risk factor for cardiovascular disease. Its role in DPN is not well-established. We studied the associations of apoC-III, endothelial function and DPN. In patients with T2D, anthropometric data, fasting blood, and urine were collected for biochemistry and urine albumin/creatinine measurements (uACR). Endothelial function assessments were performed by laser Doppler flowmetry/imaging. DPN was considered present if there was an abnormal finding in monofilament (≤8 of 10 points) or neurothesiometer testing≥25V on either foot. Plasma apoC-III was assessed by ELISA. Monofilament and neurothesiometer readings were measured in 1981 patients, mean age 57.4±10.8 years old. DPN prevalence was 10.8% (n=214). Patients with DPN compared to those without, were significantly older (p<0.0001), with longer duration of T2D (p<0.0001), had higher BMI (p=0.006), higher glucose (p=0.015) and HbA1c (p<0.0001), Systolic blood pressure (SBP) (p<0.0001), lower eGFR (p<0.0001), higher urine ACR (p<0.0001), poorer endothelium-dependent and endothelium-independent vasodilation (both p<0.0001), higher VCAM-1 (p<0.0001) and higher apoC-III [285.3 (195.2-405.6) vs 242.9(165.0-344.0) μg/ml]. After adjustment, log transformed apoC-III, remained independently associated with the presence of DPN (B=0.965, SE=0.397, p=0.015). Plasma apoC-III is higher in patients with DPN. Apart from its known association with lipids and macrovascular complications, this study suggests its association with DPN. Whether regulating apoC-III metabolism may be an important new therapeutic approach to managing dyslipidemia and microvascular complications in T2D remains to be proven in future mechanistic and clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Anti-ischemic activity and endothelium-dependent vasorelaxant effect of hydrolysable tannins from the leaves of Rhus coriaria (Sumac) in isolated rabbit heart and thoracic aorta.

    PubMed

    Beretta, Giangiacomo; Rossoni, Giuseppe; Santagati, Natale Alfredo; Facino, Roberto Maffei

    2009-11-01

    The aim of this work was to investigate the cardioprotective activity of hydrolysable gallotannins from Rhus coriaria L. leaves extract (RCLE) in isolated rabbit heart preparations, submitted to low-flow ischemia/reperfusion damage. RCLE induces a dose-dependent normalization of coronary perfusion pressure (CPP), reducing left ventricular contracture during ischemia, and improving left ventricular developed pressure and the maximum rate of rise and fall of left ventricular pressure at reperfusion. Creatinine kinase (CK) and lactate dehydrogenase (LDH) outflow were significantly reduced during reperfusion. In parallel there was a rise in the release of the cytoprotective 6-ketoprostaglandin F (1alpha) (6-keto-PGF (1alpha)) and a decrease of tumor necrosis factor-alpha (TNF-alpha), both significant only at the highest RCLE concentrations (150-500 microg/mL). The vasorelaxant activity of RCLE was studied in isolated rabbit aorta rings precontracted with norepinephrine (NE) with and without endothelium. The vasorelaxation induced by RCLE was predominantly endothelium-dependent as demonstrated by the loss of RCLE vasorelaxant ability in i) de-endothelized rings and ii) in intact aortic rings after pretreatment with NG-monomethyl- L-arginine (L-NMMA) and 1 H-[1.2.4]oxadiazolo[4.3- A]quinoxalin-1-one (ODQ). The inhibition of vasorelaxation in intact rings by indomethacin (INDO) demonstrates the ability of RCLE to modulate the coronary endothelium cyclooxygenase (COX) pathway. The K-ATP channel antagonist glibenclamide (GLIB) was ineffective. The antioxidant activity of RCLE, investigated in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) model and in living cell systems (rat erythrocytes), was stronger than that of gallic acid, ascorbic acid and trolox. The structure of its main bioactive constituents, profiled by HPLC-ESI-HR-S, comprised a mixture of polygalloylated D-glucopyranose with different degrees of galloylation and 3- O-methylgallic acid. The cardiovascular protective

  7. Kinetic studies of desensitization and resensitization of the relaxation response to beta-2 adrenoceptor agonists in isolated guinea pig trachea.

    PubMed

    Wachsman, D E; Kavaler, J P; Sugár, I P; Schachter, E N; Gonsiorek, W; Maayani, S

    1997-01-01

    Activation of beta-2 adrenoceptors (BAR) in smooth muscle preparations is associated with a rapid, reversible and incomplete receptor desensitization, resulting in a steady-state relaxation response to BAR agonists. Based on results from cell culture studies, we hypothesize that, in the isolated guinea pig trachea, this steady state is a result of a concurrent resensitization of desensitizing BAR. In tracheal segments maintained at mechanical tone (4-6 g), isoproterenol (ISO) and the partial BAR agonist salbutamol (SALB) elicited a monotonic, rapid (1-3 min) and reproducible relaxation response that could be maintained for up to 45 min and was completely reversed by propranolol. Similarly, tissues preconstricted with 0.1 microM carbachol (CARB) responded with a sustained relaxation response to ISO. In contrast, in tissues preconstricted with 0.3 to 10 microM CARB or with 75 mM KCl, the relaxation elicited by ISO was followed by a slow (20-30 min) and partial restoration of muscle tone ("fade"). The relaxation and fade were observed when CARB-constricted tissues were relaxed with SALB (0.2 or 10 microM) or 10 microM salmeterol. No response to SALB was observed when tissues were preconstricted with KCl. The fade met criteria for its classification as a homologous desensitization of the relaxation response at the BAR level. In desensitized washed tissues, a complete recovery of the original relaxation response could be detected within 60 min of drug removal. A propranolol- and ICI 118-551-sensitive steady state was achieved 30 to 35 min after the addition of BAR agonists to the isolated tissues. A three-compartment phenomenological kinetic model accurately described the observed data, defining one steady-state and three rate constants, describing relaxation (k1), desensitization (k2) and resensitization (k3). The values of k2 and k3 for the response to SALB and to salmeterol were significantly larger than those observed for ISO. In the presence of KCl, the values of k

  8. The induction of nitric oxide-mediated relaxation of human isolated pulmonary arteries by PACAP

    PubMed Central

    Cardell, Lars Olaf; Hjert, Ola; Uddman, Rolf

    1997-01-01

    The effects of pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) were analysed in human isolated circular segments of pulmonary arteries. Guinea-pig pulmonary arteries were used for comparison. The responses obtained were analysed in relation to the vascular endothelium and the nitric oxide (NO) synthase inhibitor NG-monomethyl L-arginine (L-NMMA).PACAP and VIP induced concentration-dependent relaxations of precontracted pulmonary arteries. The maximal dilator response (Imax,%) and the potency (pEC50 value) were the same for both peptides, and there were no differences in the effects obtained on human and guinea-pig segments. PACAP and VIP were both more potent that acetylcholine (ACh).Removal of the vascular endothelium abolished the PACAP induced dilator response in pulmonary arteries from both species. The VIP induced dilatation was unaffected, whereas the response to ACh was abolished. L-NMMA given before PACAP inhibited the dilatation. Furthermore, L-NMMA also reversed the dilatation already induced by PACAP and excess concentrations of L-arginine restored the dilator response of the L-NMMA treated arteries.PACAP is a potent dilator of human pulmonary arteries. Although the dilator effect seems to be similar in amplitude to the one induced by VIP, the present results suggest differences in the underlying mechanisms of action (endothelium-dependency) between the two peptides. PMID:9134222

  9. The comparative effects of aminoglycoside antibiotics and muscle relaxants on electrical field stimulation response in rat bladder smooth muscle.

    PubMed

    Min, Chang Ho; Min, Young Sil; Lee, Sang Joon; Sohn, Uy Dong

    2016-06-01

    It has been reported that several aminoglycoside antibiotics have a potential of prolonging the action of non-depolarizing muscle relaxants by drug interactions acting pre-synaptically to inhibit acetylcholine release, but antibiotics itself also have a strong effect on relaxing the smooth muscle. In this study, four antibiotics of aminoglycosides such as gentamicin, streptomycin, kanamycin and neomycin were compared with skeletal muscle relaxants baclofen, tubocurarine, pancuronium and succinylcholine, and a smooth muscle relaxant, papaverine. The muscle strips isolated from the rat bladder were stimulated with pulse trains of 40 V in amplitude and 10 s in duration, with pulse duration of 1 ms at the frequency of 1-8 Hz, at 1, 2, 4, 6, 8 Hz respectively. To test the effect of four antibiotics on bladder smooth muscle relaxation, each of them was treated cumulatively from 1 μM to 0.1 mM with an interval of 5 min. Among the four antibiotics, gentamicin and neomycin inhibited the EFS response. The skeletal muscle relaxants (baclofen, tubocurarine, pancuronium and succinylcholine) and inhibitory neurotransmitters (GABA and glycine) did not show any significant effect. However, papaverine, had a significant effect in the relaxation of the smooth muscle. It was suggested that the aminoglycoside antibiotics have inhibitory effect on the bladder smooth muscle.

  10. Design and synthesis of calcium responsive magnetic resonance imaging agent: Its relaxation and luminescence studies.

    PubMed

    Tanwar, Jyoti; Datta, Anupama; Chauhan, Kanchan; Kumaran, S Senthil; Tiwari, Anjani K; Kadiyala, K Ganesh; Pal, Sunil; Thirumal, M; Mishra, Anil K

    2014-07-23

    Calcium concentration modulation both inside and outside cell is of considerable interest for nervous system function in normal and pathological conditions. MRI has potential for very high spatial resolution at molecular/cellular level. Design, synthesis and evaluation of Gd-DO3A-AME-NPHE, a calcium responsive MRI contrast agent is presented. The probe is comprised of a Gd(3+)-DO3A core coupled to iminoacetate coordinating groups for calcium induced relaxivity switching. In the absence of Ca(2+) ions, inner sphere water binding to the Gd-DO3A-AME-NPHE is restricted with longitudinal relaxivity, r1 = 4.37 mM(-1) s(-1) at 4.7 T. However, addition of Ca(2+) triggers a marked enhancement in r1 = 6.99 mM(-1) s(-1) at 4.7 T (60% increase). The construct is highly selective for Ca(2+) over competitive metal ions at extracellular concentration. The r1 is modulated by changes in the hydration number (0.2 to 1.05), which was confirmed by luminescence emission lifetimes of the analogous Eu(3+) complex. T1 phantom images establish the capability of complex of visualizing changes in [Ca(2+)] by MRI.

  11. Temporal relaxation of nonequilibrium in Y-Ba-Cu-O measured from transient photoimpedance response

    SciTech Connect

    Bluzer, N. )

    1991-11-01

    Nonequilibrium in Y-Ba-Cu-O thin films biased with a dc current is photoinduced by exposure to 300-fsec 2-eV laser pulses. The photoinduced nonequilibrium transients were measured in the superconducting, transition, and normal states occurring between 7 and 200 K. The photoabsorption produced temporal changes in the sample's impedance, which manifest themselves as transient voltage signals occurring across the samples during the nonequilibrium's relaxation process. At and above {ital T}{sub {ital c}}, the observed photoresponse is thermal. Below {ital T}{sub {ital c}}, a quantum response is obtained corresponding to changes in the Cooper-pair populations. In the zero-resistance superconducting state, a positive signal corresponds to quasiparticle generation and a negative signal corresponds to quasiparticle recombination.

  12. Nonlinear structural response using adaptive dynamic relaxation on a massively-parallel-processing system

    NASA Technical Reports Server (NTRS)

    Oakley, David R.; Knight, Norman F., Jr.

    1994-01-01

    A parallel adaptive dynamic relaxation (ADR) algorithm has been developed for nonlinear structural analysis. This algorithm has minimal memory requirements, is easily parallelizable and scalable to many processors, and is generally very reliable and efficient for highly nonlinear problems. Performance evaluations on single-processor computers have shown that the ADR algorithm is reliable and highly vectorizable, and that it is competitive with direct solution methods for the highly nonlinear problems considered. The present algorithm is implemented on the 512-processor Intel Touchstone DELTA system at Caltech, and it is designed to minimize the extent and frequency of interprocessor communication. The algorithm has been used to solve for the nonlinear static response of two and three dimensional hyperelastic systems involving contact. Impressive relative speedups have been achieved and demonstrate the high scalability of the ADR algorithm. For the class of problems addressed, the ADR algorithm represents a very promising approach for parallel-vector processing.

  13. Sodium nitrite causes relaxation of the isolated rat aorta: By stimulating both endothelial NO synthase and activating soluble guanylyl cyclase in vascular smooth muscle.

    PubMed

    Ling, Wei Chih; Lau, Yeh Siang; Murugan, Dharmani Devi; Vanhoutte, Paul M; Mustafa, Mohd Rais

    2015-11-01

    Ingestion of dietary nitrites lowers arterial blood pressure in experimental animals and in humans. However, the exact mechanism underlying the hypotensive effect of nitrite remains unclear. The present study compared nitrite-induced responses in rings (with or without endothelium) of aortae of 18-20weeks old Wistar-Kyoto Rats (WKY) and spontaneously hypertensive (SHR) rats and investigated the underlying mechanism. Relaxations of aortae from WKY and SHR to increasing concentrations (1nM-100μM) of sodium nitrite (NaNO2) were determined during sustained contractions to phenylephrine, in the absence and presence of pharmacological agents. The nitrite-induced relaxations were concentration-dependent and larger in SHR than in WKY aortic rings. Inhibition of endothelial nitric oxide synthase (eNOS) and the absence of endothelium decreased nitrite-induced relaxations in both WKY and SHR aortae, indicating the role of endothelium-derived nitric oxide (NO) in the response. The involvement of eNOS was further confirmed by increases in phosphorylation of eNOS at ser1177 in HUVEC cells following treatment with sodium nitrite. The presence of NO scavengers decreased the relaxation to nitrite in both WKY and SHR preparations while inhibition of soluble guanylyl cyclase (sGC) abolished the response, indicating that besides producing NO, nitrite also induces relaxation by directly activating the enzyme. Thus, the present study demonstrates that the sensitivity to exogenous nitrite is increased in the aorta of the SHR compared to that of the WKY. The endothelium-dependent component of the relaxation to nitrite involves activation of eNOS with production of endothelium-derived NO, while the endothelium-independent component is due to stimulation of sGC. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Comparison of endothelium-dependent and -independent vasomotor response after abluminal biodegradable polymer biolimus-eluting stent and persistent polymer everolimus-eluting stent implantation (COMPARE-IT).

    PubMed

    Puricel, Serban; Kallinikou, Zacharenia; Espinola, Jaqueline; Arroyo, Diego; Goy, Jean-Jacques; Stauffer, Jean-Christophe; Baeriswyl, Gérard; Smits, Pieter Cornelis; Cook, Stéphane; Togni, Mario

    2016-01-01

    Drug-eluting stents (DES) have been associated with local endothelial dysfunction in the segments proximal and distal to the stent (peristent segments) and increased thrombotic risk in long term follow-up. Little data exists on endothelial function post-implantation of new DES with biodegradable polymer. The aim of our study was to compare the local endothelial function assessed by exercise induced coronary vasomotion after implantation of a biolimus A9-eluting stent with biodegradable polymer (BES) with an everolimus-eluting stent with durable polymer (EES). Coronary vasomotion was evaluated with quantitative coronary angiography at rest and during supine bicycle exercise in nine patients with EES and thirteen patients with BES, 16 months after stent implantation. Mean luminal diameter of the stent, peristent segments, and of a control vessel were determined at rest, during exercise, and after the administration of nitroglycerine. The control vessel showed exercise-induced vasodilatation in both groups (EES: +6.4±5.5%, p=0.07; BES: +7.8±10.1%, p=0.07). Vasomotion in the stented vessel segment was abolished. There was exercise-induced vasoconstriction in both groups in the segments proximal (EES: -9.6±4.5%; p=0.03; BES: -4.3±5.4%, p=0.02) and distal to the stent (EES: -3.2±9.3%; p=0.41, BES -8.6±8.0%, p<0.01). Sublingual nitroglycerin was associated with maximal vasodilatation of the peristent segments in both groups. Alike DES with durable polymer, stents with a biodegradable polymer are associated with exercise-induced paradoxical coronary vasoconstriction of the peristent segments. This data suggests that endothelial dysfunction after DES implantation is not primarily caused by the durability of the polymer coating. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Leaf trichome responses to herbivory in willows: induction, relaxation and costs.

    PubMed

    Björkman, Christer; Dalin, Peter; Ahrné, Karin

    2008-01-01

    To circumvent the inherent problem of discriminating between the cost of losing photosynthetic tissue and the cost of producing an inducible defence, the growth response of herbivore-damaged plants was compared with plants damaged mechanically to the same extent but without eliciting the defence. Two experiments were conducted, studying the response of willows (Salix cinerea) to damage by adult leaf beetles (Phratora vulgatissima). In the first experiment, willows produced new leaves with an enhanced leaf trichome density 10-20 d after damage, coinciding in time with the feeding of beetle offspring. The response was relaxed in foliage produced 30-40 d after damage. In the second experiment, which also included mechanical damage, willows exposed to beetle feeding showed an increase in leaf trichome density of the same magnitude (> 70%) as in the first experiment. The cost of producing the defence was a 20% reduction in shoot length growth and biomass production. Willows exposed to mechanical damage had an 8% reduction in shoot length growth compared with control plants, that is, a cost of leaf area removal. The results are the first quantitative estimates of the cost of a plant defence induced by natural and low amounts (3.3%) of herbivory.

  16. Stress-relaxation response of human menisci under confined compression conditions.

    PubMed

    Martin Seitz, Andreas; Galbusera, Fabio; Krais, Carina; Ignatius, Anita; Dürselen, Lutz

    2013-10-01

    The objective of this study was to determine the viscoelastic properties of human meniscal tissue during stress-relaxation under confined compression conditions. Lateral and medial longitudinal meniscus plugs of 25 donor knees (ntotal=150) were exposed to stress-relaxation tests under confined compression conditions at three compression levels (ε=0.1; 0.15; 0.2). Mathematical modelling using an exponential 1D-diffusion equation was used to predict the viscoelastic properties. Subsequently, finite element (FE) models were created using identical geometry, properties and test conditions as used for the in-vitro tests. Two constitutively different underlying mathematical formulations were applied to the FE models to reveal possible differences in their predictions for the relaxation response. While the first FE model mimicked the analytical model (FE1), the second FE model used a different biphasic, non-linear approach (FE2). Regression analyses showed promising coefficients of determination (R(2)>0.73) between the experimental data and the predictions obtained from the diffusion equation and the two FE models. Mean aggregate modulus, predicted with the diffusion equation (HA=64.0 kPa) was lower than those obtained with the two FE analyses (HA,FE1=91.9 kPa; HA,FE2=81.5 kPa). Mean hydraulic permeability (kFE2=1.5×10(-15)m(4)/Ns) of the second FE2 approach was statistically lower (p<0.01) than the other permeability values (k=3.9×10(-15)m(4)/Ns; kFE1=3.4×10(-15)m(4)/Ns). These differences are mainly due to the different underlying mathematical models used. However, when compared with corresponding literature, the results of the present study indicated good agreement. The results of the present study contribute to a better understanding of the complex nature of meniscal tissue and might also have an impact on the design of future meniscal substitutes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Relaxation of human isolated mesenteric arteries by vasopressin and desmopressin.

    PubMed Central

    Martínez, M C; Vila, J M; Aldasoro, M; Medina, P; Flor, B; Lluch, S

    1994-01-01

    1. The effects of vasopressin and deamino-8-D-arginine vasopressin (DDAVP, desmopressin) were studied in artery rings (0.8-1 mm in external diameter) obtained from portions of human omentum during the course of abdominal operations (27 patients). 2. In arterial rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with an EC50 of 0.59 +/- 0.12 nM. The V1 antagonist d(CH2)5Tyr(Me)AVP (1 microM) and the mixed V1-V2 antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (0.01 microM) displaced the control curve to vasopressin to the right in a parallel manner without differences in the maximal responses. In the presence of indomethacin (1 microM) the contractile response to vasopressin was significantly increased (P < 0.01). 3. In precontracted arterial rings, previously treated with the V1 antagonist, d(CH2)5Tyr(Me)AVP (1 microM), vasopressin produced endothelium-dependent relaxation. This relaxation was reduced significantly (P < 0.05) by indomethacin (1 microM) and unaffected by the V1-V2 receptor antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (1 microM) or by NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM). 4. The selective V2 receptor agonist, DDAVP, caused endothelium-independent, concentration-dependent relaxations in precontracted arterial rings that were inhibited by the mixed V1-V2 receptor antagonist, but not by the V1 receptor antagonist or by pretreatment with indomethacin or L-NAME. 5. Results from this study suggest that vasopressin is primarily a constrictor of human mesenteric arteries by V1 receptor stimulation; vasopressin causes dilatation only during V1 receptor blockade. The relaxation appears to be mediated by the release of vasodilator prostaglandins from the endothelial cell layer and is independent of V2 receptor stimulation or release of nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7834191

  18. Predicting Differential Response to EMG Biofeedback and Relaxation Training: The Role of Cognitive Structure.

    ERIC Educational Resources Information Center

    Hart, James D.

    1984-01-01

    Analyzed treatment outcome data for 102 headache patients who had been assigned randomly to receive either EMG biofeedback (N=70) or relaxation training (N=32). Analysis demonstrated that relaxation training was significantly more effective than biofeedback and that mixed headache patients improved significantly less than either migraine or…

  19. Predicting Differential Response to EMG Biofeedback and Relaxation Training: The Role of Cognitive Structure.

    ERIC Educational Resources Information Center

    Hart, James D.

    1984-01-01

    Analyzed treatment outcome data for 102 headache patients who had been assigned randomly to receive either EMG biofeedback (N=70) or relaxation training (N=32). Analysis demonstrated that relaxation training was significantly more effective than biofeedback and that mixed headache patients improved significantly less than either migraine or…

  20. Mechanisms underlying the relaxation response induced by bradykinin in the epithelium-intact guinea-pig trachea in vitro

    PubMed Central

    Schlemper, Valfredo; Medeiros, Rodrigo; Ferreira, Juliano; Campos, Maria M; Calixto, João B

    2005-01-01

    In this study, we investigated some of the signalling pathways involved in bradykinin (BK)-induced relaxation in epithelium-intact strips of the guinea-pig trachea (GPT+E). BK induced time- and concentration-dependent relaxation of GPT+E. Similar responses were observed for prostaglandin E2 (PGE2) or the combination of subthreshold concentrations of BK plus PGE2. The nonselective cyclooxygenase (COX) inhibitors indomethacin or pyroxicam, or the selective COX-2 inhibitors DFU, NS 398 or rofecoxib, but not the selective COX-1 inhibitor SC 560, all abolished BK-induced relaxation. The tyrosine kinase inhibitors herbimycin A and AG 490 also abolished BK-induced relaxation in GPT+E. The nonselective nitric oxide synthase (NOS) inhibitor 7-NINA concentration-dependently inhibited BK effects. BK-induced relaxation was prevented by the selective antagonists for EP3 (L 826266), but not by EP1 (SC 19221), EP1/EP2 (AH 6809) or EP4 (L 161982) receptor antagonists. Otherwise, the selective inhibitors of protein kinases A, G and C, mitogen-activated protein kinases, phospholipases C and A2, nuclear factor-κB or potassium channels all failed to significantly interfere with BK-mediated relaxation. BK caused a marked increase in PGE2 levels, an effect that was prevented by NS 398, HOE 140 or AG 490. COX-2 expression did not differ in preparations with or without epithelium, and it was not changed by BK stimulation. However, incubation with BK significantly increased the endothelial NOS (eNOS) and neuronal NOS (nNOS) expression, independent of the epithelium integrity. Our results indicate that BK-induced relaxation in GPT+E depends on prostanoids (probably PGE2 acting via EP3 receptors) and NO release and seems to involve complex interactions between kinin B2 receptors, COX-2, nNOS, eNOS and tyrosine kinases. PMID:15852038

  1. Dietary phytoestrogen improves relaxant responses to 17-β-estradiol in aged but not ovariectomised rat bladders.

    PubMed

    Owen, Suzzanne J; Massa, Helen M; Rose'Meyer, Roselyn B

    2013-10-01

    This study examined the effect of age, ovariectomy and dietary phytoestrogen ingestion on 17-β-estradiol-mediated relaxant responses and messenger RNA (mRNA) and protein expression of oestrogen receptor subtypes in the rat isolated bladder. Female Wistar rats (8 weeks) were anaesthetised, and the ovaries were removed (ovx) or left intact (sham). Rats were fed either normal rat chow (soy, phytoestrogens) or a non-soy (phytoestrogen free) diet. Isolated bladder from rats aged 12, 24 or 52 weeks were pre-contracted with 3 μM carbachol prior to obtaining a concentration response curve to 17-β-estradiol. Protein and mRNA expression of the oestrogen receptor subtypes was completed using immunohistochemistry and real-time PCR, respectively. Relatively moderate relaxant responses to 17-β-estradiol were observed in bladders from all age and treatment groups. However, in soy-fed sham 52-week-old rats, the bladder exhibited enhanced relaxant responses to 17-β-estradiol when compared to tissues from other age-matched rat treatment groups (P < 0.05). In bladders from female rats, the mRNA and protein expression of oestrogen receptors β was significantly greater than the expression of the oestrogen receptor α. Oestrogen receptor α mRNA expression declined with age (P < 0.05), whereas oestrogen receptor β expression did not change in any of the treatment groups (P > 0.05). Diet, overiectomy or age did not alter the protein expression of either oestrogen receptor subtype in the bladder (P > 0.05). While a soy diet improved relaxant effects to the 17-β-estradiol with age, it did not alter relaxant responses in bladders from ovariectomised rats.

  2. Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways.

    PubMed

    Bhasin, Manoj K; Dusek, Jeffery A; Chang, Bei-Hung; Joseph, Marie G; Denninger, John W; Fricchione, Gregory L; Benson, Herbert; Libermann, Towia A

    2013-01-01

    The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress.

  3. Relaxation Response Induces Temporal Transcriptome Changes in Energy Metabolism, Insulin Secretion and Inflammatory Pathways

    PubMed Central

    Joseph, Marie G.; Denninger, John W.; Fricchione, Gregory L.; Benson, Herbert; Libermann, Towia A.

    2013-01-01

    The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress. PMID:23650531

  4. Relaxation response with acupuncture trial in patients with HIV: feasibility and participant experiences.

    PubMed

    Chang, Bei-Hung; Boehmer, Ulrike; Zhao, Yue; Sommers, Elizabeth

    2007-09-01

    The study of complementary and alternative medicine (CAM) using a randomized, controlled trial (RCT) design poses challenges, such as treatment standardization and blinding. We designed an RCT, which avoided these two common challenges, to evaluate the effect of adding the relaxation response (RR) to usual acupuncture treatment. In this paper, we report on the feasibility and patients' experience from the study participation. Our study was a two-arm, double-blind RCT conducted in an acupuncture clinic in Boston. Study subjects were patients with human immunodeficiency virus/autoimmunodeficiency syndrome (HIV/AIDS), who reported having at least one of the highly prevalent HIV-related symptoms, and were receiving acupuncture treatment. The intervention group wore earphones to listen to tapes with instructions to elicit the RR and also soft music while receiving acupuncture treatment, while the control group only listened to soft music. The intervention group was also required to listen to the RR tapes at home daily. A study evaluation was completed upon termination of the 12-week study (36 intervention and 44 control patients). A majority of participants in both groups reported: no discomfort wearing earphones (82.9%, 81.8%); the study met their expectations (87.1%, 85.4%); and they would recommend the study to others (91.1%, 90.5%). Intervention participants reported better experiences with the tapes than the control group (p = 0.056) (72.4% versus 52.8% felt better with tapes; 3.5% versus 16.7% felt better without tapes; and 24.1% versus 30.6% felt no difference). Intervention participants were also more likely than the control group (p = 0.02) to report positive emotional/physical/spiritual changes (45.5% vs. 20.9%) and relaxed/peaceful/calm feelings (30.3% vs. 25.6%) from the study participation. We demonstrated the feasibility of conducting a unique trial that examined the synergistic effects of two types of CAM practices. The intervention group reported more

  5. Relaxation Response with Acupuncture Trial in Patients with HIV: Feasibility and Participant Experiences

    PubMed Central

    CHANG, BEI-HUNG; BOEHMER, ULRIKE; ZHAO, YUE; SOMMERS, ELIZABETH

    2010-01-01

    Objectives The study of complementary and alternative medicine (CAM) using a randomized, controlled trial (RCT) design poses challenges, such as treatment standardization and blinding. We designed an RCT, which avoided these two common challenges, to evaluate the effect of adding the relaxation response (RR) to usual acupuncture treatment. In this paper, we report on the feasibility and patients’ experience from the study participation. Design, setting, and subjects Our study was a two-arm, double-blind RCT conducted in an acupuncture clinic in Boston. Study subjects were patients with human immunodeficiency virus/autoimmunodeficiency syndrome (HIV/AIDS), who reported having at least one of the highly prevalent HIV-related symptoms, and were receiving acupuncture treatment. Intervention The intervention group wore earphones to listen to tapes with instructions to elicit the RR and also soft music while receiving acupuncture treatment, while the control group only listened to soft music. The intervention group was also required to listen to the RR tapes at home daily. Outcome measures A study evaluation was completed upon termination of the 12-week study (36 intervention and 44 control patients). Results A majority of participants in both groups reported: no discomfort wearing earphones (82.9%, 81.8%); the study met their expectations (87.1%, 85.4%); and they would recommend the study to others (91.1%, 90.5%). Intervention participants reported better experiences with the tapes than the control group (p = 0.056) (72.4% versus 52.8% felt better with tapes; 3.5% versus 16.7% felt better without tapes; and 24.1% versus 30.6% felt no difference). Intervention participants were also more likely than the control group (p = 0.02) to report positive emotional/physical/spiritual changes (45.5% vs. 20.9%) and relaxed/peaceful/calm feelings (30.3% vs. 25.6%) from the study participation. Conclusions We demonstrated the feasibility of conducting a unique trial that examined

  6. TNF-α knockout mice have increased corpora cavernosa relaxation

    PubMed Central

    2010-01-01

    Introduction Erectile dysfunction (ED) is considered an early clinical manifestation of vascular disease and an independent risk factor for cardiovascular events associated with endothelial dysfunction and increased levels of pro-inflammatory cytokines. Tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, suppresses endothelial nitric oxide synthase (eNOS) expression. Aim Considering that nitric oxide (NO) is of critical importance in penile erection, we hypothesized that blockade of TNF-α actions would increase cavernosal smooth muscle relaxation through an increase in NOS expression. Methods In vitro organ bath studies were used to measure cavernosal reactivity in wild type and TNF-α knockout (TNF-α KO) mice and NOS expression was evaluated by western blot. In addition, spontaneous erections (in vivo) were evaluated by videomonitoring the animals (30 min.). Collagen and elastin expression were evaluated by Masson trichrome and Verhoff-van Gieson stain reaction, respectively. Main Outcome Measures Corpora cavernosa from TNF-α KO mice exhibited increased NO-dependent relaxation, which was associated with increased eNOS and neuronal NOS (nNOS) cavernosal expression. Results Cavernosal strips from TNF-α KO mice displayed increased endothelium-dependent [97.4±5.3 vs Control: 76.3±6.3, %] and nonadrenergic-noncholinergic (NANC) [93.3±3.0 vs Control: 67.5±16.0; 16 Hz] relaxation compared to control animals. These responses were associated with increased protein expression of eNOS and nNOS (p<0.05). Sympathetic-mediated [0.69±0.16 vs Control: 1.22±0.22; 16 Hz] as well as phenylephrine-induced contractile responses [1.6±0.1 vs Control: 2.5±0.1, mN] were attenuated in cavernosal strips from TNF-α KO mice. Additionally, corpora cavernosa from TNF-α KO mice displayed increased collagen and elastin expression. In vivo experiments demonstrated that TNF-α KO mice display increased number of spontaneous erections. Conclusion Corpora cavernosa from

  7. In vitro relaxation of dog cerebral veins in response to histamine is mediated by histamine H2 receptors.

    PubMed

    Monge, L; García-Villalón, A L; Fernández, N; García, J L; Gómez, B; Diéguez, G

    1997-11-05

    There is little information on the histamine receptor mechanisms involved in cerebral venodilation, thus the role of histamine present in human cerebrospinal fluid is difficult to assess. In isolated canine pial veins, concentration-response curves to histamine (10[-7]-10[-3] M), the histamine H1 receptor agonist, 2-pyridylethylamine (10[-6]-10[-2] M), the histamine H2 receptor agonist, dimaprit (S-(3-dimethylaminopropyl) isothiourea dihydrochloride, 10[-6]-10[-2] M), and the histamine H3 receptor agonist, imetit (S-[2-(1 midazol-4-yl)ethyl]isothiourea dihydrobromide, 10[-7]-10[-3] M) were isometrically determined. In resting veins, histamine, 2-pyridylethylamine and dimaprit had no significant effect, whereas in endothelin-1-precontracted veins, these drugs produced concentration-dependent relaxation (Emax in % of active tone and pD2 were: for histamine, 72 +/- 6 and 5.36 +/- 0.09; for 2-pyridylethylamine, 59 +/- 5 and 3.28 +/- 0.05; for dimaprit, 65 +/- 7 and 4.81 +/- 0.10, respectively). The relaxations in response to histamine and dimaprit were competitively antagonized by the histamine H2 receptor antagonist, cimetidine (3 x 10[-6]-10[-4] M) (pA2 = 6.07 +/- 0.03 for histamine, and 6.09 +/- 0.07 for dimaprit), but were not affected by the histamine H1 receptor antagonist, chlorpheniramine (10[-6] M) or the histamine H3 receptor antagonist, thioperamide (N-cyclohexyl-4-(1-H-imidazol-4-yl)-1-piperidine-carbothioamide maleate, 10[-6] M). The relaxation in response to 2-pyridylethylamine was inhibited by cimetidine (10[-5] M), but not by chlorpheniramine (10[-6] M). Imetit produced a small contraction in resting veins (14 +/- 4 mg) and precontracted veins (20 +/- 3 mg), which was not modified by thioperamide (10[-6] M). The relaxation of veins in response to histamine was not modified by endothelium removal, nor by the inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester (10[-4] M), or the cyclooxygenase inhibitor, meclofenamate (10[-5] M

  8. GAG depletion increases the stress-relaxation response of tendon fascicles, but does not influence recovery.

    PubMed

    Legerlotz, Kirsten; Riley, Graham P; Screen, Hazel R C

    2013-06-01

    Cyclic and static loading regimes are commonly used to study tenocyte metabolism in vitro and to improve our understanding of exercise-associated tendon pathologies. The aims of our study were to investigate if cyclic and static stress relaxation affected the mechanical properties of tendon fascicles differently, if this effect was reversible after a recovery period, and if the removal of glycosaminoglycans (GAGs) affected sample recovery. Tendon fascicles were dissected frombovine-foot extensors and subjected to 14% cyclic (1Hz) or static tensile strain for 30min. Additional fascicles were incubated overnight in buffer with 0.5U chondroitinase ABC or in buffer alone prior to the static stress-relaxation regime. To assess the effect of different stress-relaxation regimes, a quasi-static test to failure was carried out, either directly post loading or after a 2h recovery period, and compared with unloaded control fascicles. Both stress-relaxation regimes led to a significant reduction in fascicle failure stress and strain, but this was more pronounced in the cyclically loaded specimens. Removal of GAGs led to more stress relaxation and greater reductions in failure stress after static loading compared to controls. The reduction in mechanical properties was partially reversible in all samples, given a recovery period of 2h. This has implications for mechanical testing protocols, as a time delay between fatiguing specimens and characterization of mechanical properties will affect the results. GAGs appear to protect tendon fascicles from fatigue effects, possibly by enabling sample hydration.

  9. Effectiveness of the relaxation response-based group intervention for treating depressed chinese american immigrants: a pilot study.

    PubMed

    Yeung, Albert; Slipp, Lauren E; Niles, Halsey; Jacquart, Jolene; Chow, Choi-Ling; Fava, Maurizio; Denninger, John W; Benson, Herbert; Fricchione, Gregory L

    2014-09-05

    This study examined the feasibility, safety and efficacy of an 8-week Relaxation Response (RR)-based group. Twenty-two depressed Chinese American immigrants were recruited. Outcomes measures were response and remission rates, the Hamilton Rating Scale for Depression, Clinical Global Impressions Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, and the Multidimensional Scale of Perceived Social Support Scale. Participants (N = 22) were 82% female, mean age was 53 (± 12). After intervention, completers (N = 15) showed a 40% response rate and a 27% remission rate, and statistically significant improvement in most outcome measures. The RR-based group is feasible and safe in treating Chinese American immigrants with depression.

  10. Relaxation Response and Resiliency Training and Its Effect on Healthcare Resource Utilization.

    PubMed

    Stahl, James E; Dossett, Michelle L; LaJoie, A Scott; Denninger, John W; Mehta, Darshan H; Goldman, Roberta; Fricchione, Gregory L; Benson, Herbert

    2015-01-01

    Poor psychological and physical resilience in response to stress drives a great deal of health care utilization. Mind-body interventions can reduce stress and build resiliency. The rationale for this study is therefore to estimate the effect of mind-body interventions on healthcare utilization. Estimate the effect of mind body training, specifically, the Relaxation Response Resiliency Program (3RP) on healthcare utilization. Retrospective controlled cohort observational study. Major US Academic Health Network. All patients receiving 3RP at the MGH Benson-Henry Institute from 1/12/2006 to 7/1/2014 (n = 4452), controls (n = 13149) followed for a median of 4.2 years (.85-8.4 yrs). Utilization as measured by billable encounters/year (be/yr) stratified by encounter type: clinical, imaging, laboratory and procedural, by class of chief complaint: e.g., Cardiovascular, and by site of care delivery, e.g., Emergency Department. Subgroup analysis by propensity score matched pre-intervention utilization rate. At one year, total utilization for the intervention group decreased by 43% [53.5 to 30.5 be/yr] (p <0.0001). Clinical encounters decreased by 41.9% [40 to 23.2 be/yr], imaging by 50.3% [11.5 to 5.7 be/yr], lab encounters by 43.5% [9.8 to 5.6], and procedures by 21.4% [2.2 to 1.7 be/yr], all p < 0.01. The intervention group's Emergency department (ED) visits decreased from 3.6 to 1.7/year (p<0.0001) and Hospital and Urgent care visits converged with the controls. Subgroup analysis (identically matched initial utilization rates-Intervention group: high utilizing controls) showed the intervention group significantly reduced utilization relative to the control group by: 18.3% across all functional categories, 24.7% across all site categories and 25.3% across all clinical categories. Mind body interventions such as 3RP have the potential to substantially reduce healthcare utilization at relatively low cost and thus can serve as key components in any population health and

  11. Relaxation Response and Resiliency Training and Its Effect on Healthcare Resource Utilization

    PubMed Central

    Stahl, James E.; Dossett, Michelle L.; LaJoie, A. Scott; Denninger, John W.; Mehta, Darshan H.; Goldman, Roberta; Fricchione, Gregory L.; Benson, Herbert

    2015-01-01

    Background Poor psychological and physical resilience in response to stress drives a great deal of health care utilization. Mind-body interventions can reduce stress and build resiliency. The rationale for this study is therefore to estimate the effect of mind-body interventions on healthcare utilization. Objective Estimate the effect of mind body training, specifically, the Relaxation Response Resiliency Program (3RP) on healthcare utilization. Design Retrospective controlled cohort observational study. Setting: Major US Academic Health Network. Sample: All patients receiving 3RP at the MGH Benson-Henry Institute from 1/12/2006 to 7/1/2014 (n = 4452), controls (n = 13149) followed for a median of 4.2 years (.85–8.4 yrs). Measurements: Utilization as measured by billable encounters/year (be/yr) stratified by encounter type: clinical, imaging, laboratory and procedural, by class of chief complaint: e.g., Cardiovascular, and by site of care delivery, e.g., Emergency Department. Subgroup analysis by propensity score matched pre-intervention utilization rate. Results At one year, total utilization for the intervention group decreased by 43% [53.5 to 30.5 be/yr] (p <0.0001). Clinical encounters decreased by 41.9% [40 to 23.2 be/yr], imaging by 50.3% [11.5 to 5.7 be/yr], lab encounters by 43.5% [9.8 to 5.6], and procedures by 21.4% [2.2 to 1.7 be/yr], all p < 0.01. The intervention group’s Emergency department (ED) visits decreased from 3.6 to 1.7/year (p<0.0001) and Hospital and Urgent care visits converged with the controls. Subgroup analysis (identically matched initial utilization rates—Intervention group: high utilizing controls) showed the intervention group significantly reduced utilization relative to the control group by: 18.3% across all functional categories, 24.7% across all site categories and 25.3% across all clinical categories. Conclusion Mind body interventions such as 3RP have the potential to substantially reduce healthcare utilization at

  12. Involvement of large-conductance Ca(2+) -activated K(+) channels in both nitric oxide and endothelium-derived hyperpolarization-type relaxation in human penile small arteries.

    PubMed

    Király, István; Pataricza, János; Bajory, Zoltán; Simonsen, Ulf; Varro, András; Papp, Julius Gy; Pajor, Lászlo; Kun, Attila

    2013-07-01

    Large-conductance Ca(2+) -activated K(+) channels (BKC a ), located on the vascular smooth muscle, play an important role in regulation of vascular tone. In penile corpus cavernosum tissue, opening of BKC a channels leads to relaxation of corporal smooth muscle, which is essential during erection; however, there is little information on the role of BKC a channels located in penile vascular smooth muscle. This study was designed to investigate the involvement of BKC a channels in endothelium-dependent and endothelium-independent relaxation of human intracavernous penile arteries. In human intracavernous arteries obtained in connection with transsexual operations, change in isometric force was recorded in microvascular myographs, and endothelium-dependent [nitric oxide (NO) and endothelium-derived hyperpolarization (EDH)-type] and endothelium-independent (NO-donor) relaxations were measured in contracted arteries. In penile small arteries contracted with phenylephrine, acetylcholine evoked NO- and EDH-type relaxations, which were sensitive to iberiotoxin (IbTX), a selective blocker of BKC a channels. Iberiotoxin also inhibited relaxations induced by a NO-donor, sodium nitroprusside. NS11021, a selective opener of BKC a channels, evoked pronounced relaxations that were inhibited in the presence of IbTX. NS13558, a BKC a -inactive analogue of NS11021, failed to relax human penile small arteries. Our results show that BKC a channels are involved in both NO- and EDH-type relaxation of intracavernous penile arteries obtained from healthy men. The effect of a selective opener of BKC a channels also suggests that direct activation of the channel may be an advantageous approach for treatment of impaired endothelium-dependent relaxation often associated with erectile dysfunction.

  13. Impact of shoulder position and fatigue on the flexion-relaxation response in cervical spine.

    PubMed

    Nimbarte, Ashish D; Zreiqat, Majed; Ning, Xiaopeng

    2014-03-01

    Neck pain is common among general population with a high prevalence among the people who are routinely exposed to prolonged use of static head-neck postures. Prolonged static loading can cause localized muscle fatigue which may impact the stability of the cervical spine. In this study, flexion-relaxation phenomenon was used to study the post fatigue changes in the stability of cervical spine by evaluating the synergistic load sharing between muscles and viscoelastic elements. Thirteen male participants were recruited for data collection. The variables that influence cervical flexion-relaxation were studied pre- and post-fatigue using neutral and shrugged shoulder postures. The Sorensen protocol was used to induce neck extensor fatigue. Surface electromyography and optical motion capture systems were used to record neck muscle activation and head posture, respectively. Findings The flexion-relaxation phenomenon was observed only in the neutral shoulder position pre- and post-fatigue. The flexion relaxation ratio decreased significantly post-fatigue in neutral shoulder position but remained unchanged in shrugged shoulder position. The onset and offset angles and the corresponding durations of the silence period were significantly affected by the fatigue causing a post-fatigue expansion of silence period. Interpretation The muscular fatigue of neck extensors and shoulder position was found to modulate the cervical flexion-relaxation phenomenon. Early shifting of load sharing under fatigued condition indicates increased demands on the passive tissues to stabilize the cervical spine. Shrugging of shoulder seems to alter muscular demands of neck extensors and make cervical flexion-relaxation phenomenon disappear due to continuous activation of the neck extensors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. The effect of prior lumbar surgeries on the flexion relaxation phenomenon and its responsiveness to rehabilitative treatment.

    PubMed

    Neblett, Randy; Mayer, Tom G; Brede, Emily; Gatchel, Robert J

    2014-06-01

    Abnormal pretreatment flexion-relaxation in chronic disabling occupational lumbar spinal disorder patients has been shown to improve with functional restoration rehabilitation. Little is known about the effects of prior lumbar surgeries on flexion-relaxation and its responsiveness to treatment. To quantify the effect of prior lumbar surgeries on the flexion-relaxation phenomenon and its responsiveness to rehabilitative treatment. A prospective cohort study of chronic disabling occupational lumbar spinal disorder patients, including those with and without prior lumbar spinal surgeries. A sample of 126 chronic disabling occupational lumbar spinal disorder patients with prior work-related injuries entered an interdisciplinary functional restoration program and agreed to enroll in this study. Fifty-seven patients had undergone surgical decompression or discectomy (n=32) or lumbar fusion (n=25), and the rest had no history of prior injury-related spine surgery (n=69). At post-treatment, 116 patients were reevaluated, including those with prior decompressions or discectomies (n=30), lumbar fusions (n=21), and no surgery (n=65). A comparison group of 30 pain-free control subjects was tested with an identical assessment protocol, and compared with post-rehabilitation outcomes. Mean surface electromyography (SEMG) at maximum voluntary flexion; subject achievement of flexion-relaxation (SEMG≤3.5 μV); gross lumbar, true lumbar, and pelvic flexion ROM; and a pain visual analog scale self-report during forward bending task. Identical measures were obtained at pretreatment and post-treatment. Patients entered an interdisciplinary functional restoration program, including a quantitatively directed, medically supervised exercise process and a multimodal psychosocial disability management component. The functional restoration program was accompanied by a SEMG-assisted stretching training program, designed to teach relaxation of the lumbar musculature during end-range flexion

  15. Relaxation Training and Opioid Inhibition of Blood Pressure Response to Stress.

    ERIC Educational Resources Information Center

    McCubbin, James A.; And Others

    1996-01-01

    Sought to determine the role of endogenous opioid mechanisms in the circulatory effects of relaxation training. Subjects were 32 young men with mildly elevated casual arterial pressure. Assessed opioid mechanisms by examining the effects of opioid receptor blockade with naltrexone on acute cardiovascular reactivity to laboratory stress before and…

  16. Integrating a Relaxation Response-Based Curriculum into a Public High School in Massachusetts

    ERIC Educational Resources Information Center

    Foret, Megan M.; Scult, Matthew; Wilcher, Marilyn; Chudnofsky, Rana; Malloy, Laura; Hasheminejad, Nicole; Park, Elyse R.

    2012-01-01

    Academic and societal pressures result in U.S. high school students feeling stressed. Stress management and relaxation interventions may help students increase resiliency to stress and overall well-being. The objectives of this study were to examine the feasibility (enrollment, participation and acceptability) and potential effectiveness (changes…

  17. Integrating a Relaxation Response-Based Curriculum into a Public High School in Massachusetts

    ERIC Educational Resources Information Center

    Foret, Megan M.; Scult, Matthew; Wilcher, Marilyn; Chudnofsky, Rana; Malloy, Laura; Hasheminejad, Nicole; Park, Elyse R.

    2012-01-01

    Academic and societal pressures result in U.S. high school students feeling stressed. Stress management and relaxation interventions may help students increase resiliency to stress and overall well-being. The objectives of this study were to examine the feasibility (enrollment, participation and acceptability) and potential effectiveness (changes…

  18. Relaxation Training and Opioid Inhibition of Blood Pressure Response to Stress.

    ERIC Educational Resources Information Center

    McCubbin, James A.; And Others

    1996-01-01

    Sought to determine the role of endogenous opioid mechanisms in the circulatory effects of relaxation training. Subjects were 32 young men with mildly elevated casual arterial pressure. Assessed opioid mechanisms by examining the effects of opioid receptor blockade with naltrexone on acute cardiovascular reactivity to laboratory stress before and…

  19. Chronic administration of imipramine but not agomelatine and moclobemide affects the nitrergic relaxation of rabbit corpus cavernosum smooth muscle.

    PubMed

    Gocmez, Semil Selcen; Utkan, Tijen; Gacar, Nejat

    2013-08-15

    Sexual dysfunction is a common and underestimated effect of antidepressants. However, the mechanism by which these drugs cause erectile dysfunction is unclear. We investigated the reactivity of the corpus cavernosum of rabbits that were treated with either chronic imipramine, which is a tricyclic agent; agomelatine, which is a melatonergic agonist and serotonin 5HT(2c) antagonist; or moclobemide, which is a reversible inhibitor of monoamine-oxidase A. Twenty rabbits were randomly divided into four groups: the control group (n=5), the imipramine-treated group (n=5), which received i.p. injections of 10 mg/kg/day of imipramine, the moclobemide-treated group (n=5), which received i.p. injections of 20 mg/kg/day of moclobemide, and the agomelatine-treated group (n=5), which was orally administered 10 mg/kg/day of agomelatine. The reactivities of corpus cavernosum tissue obtained from the antidepressant-treated and the control groups were studied in organ chambers after the animals were subjected to 21 days of drug administration. The acetylcholine-induced endothelium-dependent and the electrical field stimulation (EFS)-induced neurogenic relaxation of the corpus cavernosum of the imipramine-treated group was significantly decreased compared with the control group. However, neither the acetylcholine- nor EFS-induced relaxation was changed in the moclobemide- or agomelatine-treated groups. There were no change in the relaxant response to the nitric oxide (NO) donor sodium nitroprusside and contractile response to KCl between the groups. This study suggests that chronic imipramine treatment but not agomelatine and moclobemide treatments causes significant functional changes in the penile erectile tissue of rabbits and that these changes may contribute to the development of impotence.

  20. Silicic acid in drinking water prevents age-related alterations in the endothelium-dependent vascular relaxation modulating eNOS and AQP1 expression in experimental mice: an immunohistochemical study.

    PubMed

    Buffoli, Barbara; Foglio, Eleonora; Borsani, Elisa; Exley, Christopher; Rezzani, Rita; Rodella, Luigi Fabrizio

    2013-06-01

    The maintenance of endothelial integrity is of great importance in coping with age-related vascular alterations. Endothelium-derived nitric oxide is one of the various vasoactive substances able to regulate vascular tone and homeostasis, and whose decrease is known to be related with senescence in endothelial cells. There are reports on the efficacy of silicon, especially as silicic acid, in protecting vascular integrity during age-related vascular diseases. The aim of this study was to evaluate the ability of supplementation of silicic acid in drinking water in the maintenance of vascular health in a mouse model of early physiological aging. In particular, we evaluated the relationship between Si supplementation and endothelial nitric oxide synthase (eNOS) expression, taking into account also the aquaporin-1 (AQP-1) isoform that, as recently reported, seems to be involved in nitric oxide transport across cell membranes. Our results showed that silicic acid supplementation increased both eNOS and AQP-1 expression, suggesting that silicic acid modulation of endothelial nitric oxide synthase and aquaporin-1 could represent a potential strategy against age-related vascular senescence. Copyright © 2012 Elsevier GmbH. All rights reserved.

  1. Effects of a relaxation training programme on immediate and prolonged stress responses in women with preterm labour.

    PubMed

    Chuang, Li-Lan; Lin, Li-Chan; Cheng, Po-Jen; Chen, Chung-Hey; Wu, Shiao-Chi; Chang, Chuan-Lin

    2012-01-01

    This paper is a report of an experimental study of the effects of relaxation-training programme on immediate and prolonged stress responses in women with preterm labour. Hospitalized pregnant women with preterm labour experience developmental and situational stress. However, few studies have been performed on stress management in such women. An experimental pretest and repeated post-test design was used to compare the outcomes for two groups in northern Taiwan from December 2008, to May 2010. A total of 129 women were randomly assigned to an experimental (n = 68) or control (n = 61) group. The experimental group participants were instructed to listen daily to a 13-minute relaxation programme. Measurements involved the stress visual analogue scale, finger temperatures, State Trait Anxiety Inventory, Perceived Stress Scale and Pregnancy-related Anxiety. Two-way analysis of variance and hierarchical linear modelling were used to analyse the group differences. Compared with those in the control group, participants in the experimental group showed immediate improvements in the stress visual analogue scale scores and finger temperatures. The State Trait Anxiety Inventory-State subscale score for the experimental group was significantly lower than that for the control group (P = 0·03). However, no statistically significant differences for the Perceived Stress Scale and Pregnancy-related Anxiety scores were found between the experimental group and the control group. The relaxation-training programme could improve the stress responses of women with preterm labour. © 2011 The Authors. Journal of Advanced Nursing © 2011 Blackwell Publishing Ltd.

  2. Possible involvement of ATP-sensitive K+ channels in the relaxant response of dog middle cerebral artery to cromakalim

    SciTech Connect

    Masuzawa, K.; Asano, M.; Matsuda, T.; Imaizumi, Y.; Watanabe, M. )

    1990-11-01

    To determine the functions of ATP-sensitive K+ (KATP) channels in cerebral arterial smooth muscle, the effects of cromakalim, an opener of these channels, on tension and 86Rb efflux were investigated in endothelium-removed strips of dog middle cerebral arteries (MCAs). Cromakalim relaxed the strips that were precontracted with 20.9 mM K+ with a small maximum response. The relaxant responses to cromakalim were competitively antagonized by glibenclamide, a blocker of KATP channels. In strips precontracted with 65.9 mM K+, cromakalim failed to relax the strips. The addition of cromakalim to a resting strip caused a dose-dependent relaxation. In the resting strips of MCAs preloaded with 86Rb, cromakalim did not increase the 86Rb efflux. With 42K as the tracer ion, cromakalim still had no effect on the efflux from the resting strips. On the other hand, cromakalim increased the 86Rb and 42K efflux from the strips of dog coronary arteries (CAs). In 20.9 mM K(+)-contracted strips of MCAs, cromakalim significantly decreased the 86Rb efflux. However, after the inactivation of Ca(++)-activated K+ channels by the addition of 1 x 10(-7) M nifedipine to the 20.9 mM K(+)-contracted strips of MCAs, cromakalim produced a small but significant increase in the 86Rb efflux. Similarly, when the resting strips of MCAs were placed in the Ca(++)-free 12 mM-Mg(+)+ solution, cromakalim increased the 86Rb efflux. In 65.9 mM K(+)-contracted strips, cromakalim increased the 86Rb efflux from both arteries. However, the extent of the increase in 86Rb efflux was significantly smaller in the MCA than in the CA.

  3. Effect of nanofiller aspect ratio on the stress relaxation and creep response of toughened pom composites

    NASA Astrophysics Data System (ADS)

    Siengchin, S.; Sinpayakun, P.; Suttiruengwong, S.; Asawapirom, U.

    2010-09-01

    Ternary composites composed of polyoxymethylene (POM), polyurethane (PU), and sodium fluorohectorite (FH) or sodium bentonite (BN) were produced by the melt compounding masterbatch (MB) technique. The related MB was produced by mixing the PU latex with water-swellable FH or BN. The dispersion of the nanofillers in the composites was studied by X-ray diffraction techniques. The crystallization of the POM-based systems was inspected by polarized optical microscopy (PLM). The stress relaxation and creep properties of the composites were determined in short-time stress relaxation and creep tests (creep at various temperatures), respectively. The POM/PU/FH composites produced by the MB technique outperformed the POM/PU blend and the POM/PU/BN system in respect to most of the stress relaxation and creep characteristics. This fact was attributed to the higher aspect ratio of FH compared with that of BN. The master curves (creep compliance vs. time) constructed by employing the time-temperature superposition principle showed that the Findley power law was fully applicable to the experimental results obtained.

  4. Co-axial bioassay of a smooth muscle relaxant factor released from guinea-pig tracheal epithelium.

    PubMed

    Fernandes, L B; Paterson, J W; Goldie, R G

    1989-01-01

    1. The ability of guinea-pig trachea to release an epithelium-derived relaxant factor (EpDRF) was assessed in a co-axial bioassay system. 2. Histamine (100 microM) and methacholine (25 microM) caused endothelium-dependent relaxation of rat isolated aorta, presumably via the release of endothelium-derived relaxant factor (EDRF). In contrast, endothelium-denuded rat aorta did not relax in response to these agents. 3. EDRF release was detected in response to methacholine in a co-axial bioassay system, consisting of intact rabbit aorta tube (EDRF donor) and endothelium-denuded rat aorta strip (assay preparation). These results indicated the transfer of EDRF from a donor to an assay preparation, thereby validating the co-axial bioassay method. 4. Substitution of endothelium-intact rabbit aorta tube by epithelium-intact guinea-pig tracheal tube tissue in co-axial assemblies, still allowed the assay preparation to relax in response to histamine or methacholine. Removal of the intact tracheal tube from the system, or removal of the epithelium from the donor tracheal tube in co-axial preparations, abolished such relaxant responses. These observations are consistent with histamine- or methacholine-induced release of an epithelium-derived relaxant factor (EpDRF) from the trachea. 5. In the co-axial assembly comprising intact guinea-pig trachea and endothelium-denuded rat aorta, histamine and methacholine produced concentration-dependent, EpDRF-induced aortic relaxation. Mean concentrations of histamine and methacholine producing 50% of the maximum relaxation (EC50) were 39.8 microM and 2.7 microM respectively. Histamine-induced relaxation was inhibited in the presence of mepyramine (2 microM) and responses to methacholine were inhibited by atropine (0.1 microM). 6. Methylene blue (50 microM) had no effect on such relaxant responses, indicating that EpDRF does not activate guanylate cyclase. Furthermore, the cyclo-oxygenase inhibitor indomethacin (5 microM), the cyclo

  5. Strange metal from Gutzwiller correlations in infinite dimensions: Transverse transport, optical response, and rise of two relaxation rates

    NASA Astrophysics Data System (ADS)

    Ding, Wenxin; Žitko, Rok; Shastry, B. Sriram

    2017-09-01

    Using two approaches to strongly correlated systems, the extremely correlated Fermi liquid theory and the dynamical mean field theory, we compute the transverse transport coefficients, namely, the Hall constants RH and Hall angles θH, and the longitudinal and transverse optical response of the U =∞ Hubbard model in the limit of infinite dimensions. We focus on two successive low-temperature regimes, the Gutzwiller-correlated Fermi liquid (GCFL) and the Gutzwiller-correlated strange metal (GCSM). We find that the Hall angle cotθH is proportional to T2 in the GCFL regime, while upon warming into the GCSM regime it first passes through a downward bend and then continues as T2. Equivalently, RH is weakly temperature dependent in the GCFL regime, but becomes strongly temperature dependent in the GCSM regime. Drude peaks are found for both the longitudinal optical conductivity σx x(ω ) and the optical Hall angles tanθH(ω ) below certain characteristic energy scales. By comparing the relaxation rates extracted from fitting to the Drude formula, we find that in the GCFL regime there is a single relaxation rate controlling both longitudinal and transverse transport, while in the GCSM regime two different relaxation rates emerge. We trace the origin of this behavior to the dynamical particle-hole asymmetry of the Dyson self-energy, arguably a generic feature of doped Mott insulators.

  6. Disulfide-activated protein kinase G Iα regulates cardiac diastolic relaxation and fine-tunes the Frank-Starling response.

    PubMed

    Scotcher, Jenna; Prysyazhna, Oleksandra; Boguslavskyi, Andrii; Kistamas, Kornel; Hadgraft, Natasha; Martin, Eva D; Worthington, Jenny; Rudyk, Olena; Rodriguez Cutillas, Pedro; Cuello, Friederike; Shattock, Michael J; Marber, Michael S; Conte, Maria R; Greenstein, Adam; Greensmith, David J; Venetucci, Luigi; Timms, John F; Eaton, Philip

    2016-10-26

    The Frank-Starling mechanism allows the amount of blood entering the heart from the veins to be precisely matched with the amount pumped out to the arterial circulation. As the heart fills with blood during diastole, the myocardium is stretched and oxidants are produced. Here we show that protein kinase G Iα (PKGIα) is oxidant-activated during stretch and this form of the kinase selectively phosphorylates cardiac phospholamban Ser16-a site important for diastolic relaxation. We find that hearts of Cys42Ser PKGIα knock-in (KI) mice, which are resistant to PKGIα oxidation, have diastolic dysfunction and a diminished ability to couple ventricular filling with cardiac output on a beat-to-beat basis. Intracellular calcium dynamics of ventricular myocytes isolated from KI hearts are altered in a manner consistent with impaired relaxation and contractile function. We conclude that oxidation of PKGIα during myocardial stretch is crucial for diastolic relaxation and fine-tunes the Frank-Starling response.

  7. Disulfide-activated protein kinase G Iα regulates cardiac diastolic relaxation and fine-tunes the Frank–Starling response

    PubMed Central

    Scotcher, Jenna; Prysyazhna, Oleksandra; Boguslavskyi, Andrii; Kistamas, Kornel; Hadgraft, Natasha; Martin, Eva D.; Worthington, Jenny; Rudyk, Olena; Rodriguez Cutillas, Pedro; Cuello, Friederike; Shattock, Michael J.; Marber, Michael S.; Conte, Maria R.; Greenstein, Adam; Greensmith, David J.; Venetucci, Luigi; Timms, John F.; Eaton, Philip

    2016-01-01

    The Frank–Starling mechanism allows the amount of blood entering the heart from the veins to be precisely matched with the amount pumped out to the arterial circulation. As the heart fills with blood during diastole, the myocardium is stretched and oxidants are produced. Here we show that protein kinase G Iα (PKGIα) is oxidant-activated during stretch and this form of the kinase selectively phosphorylates cardiac phospholamban Ser16—a site important for diastolic relaxation. We find that hearts of Cys42Ser PKGIα knock-in (KI) mice, which are resistant to PKGIα oxidation, have diastolic dysfunction and a diminished ability to couple ventricular filling with cardiac output on a beat-to-beat basis. Intracellular calcium dynamics of ventricular myocytes isolated from KI hearts are altered in a manner consistent with impaired relaxation and contractile function. We conclude that oxidation of PKGIα during myocardial stretch is crucial for diastolic relaxation and fine-tunes the Frank–Starling response. PMID:27782102

  8. Early changes in vascular reactivity in response to 56Fe irradiation in ApoE-/- mice

    NASA Astrophysics Data System (ADS)

    White, C. Roger; Yu, Tao; Gupta, Kiran; Babitz, Stephen K.; Black, Leland L.; Kabarowski, Janusz H.; Kucik, Dennis F.

    2015-03-01

    Epidemiological studies have established that radiation from a number of terrestrial sources increases the risk of atherosclerosis. The accelerated heavy ions in the galacto-cosmic radiation (GCR) that astronauts will encounter on in space, however, interact very differently with tissues than most types of terrestrial radiation, so the health consequences of exposure on deep-space missions are not clear. We demonstrated earlier that 56Fe, an important component of cosmic radiation, accelerates atherosclerotic plaque development. In the present study, we examined an earlier, pro-atherogenic event that might be predictive of later atherosclerotic disease. Decreased endothelium-dependent vasodilation is a prominent manifestation of vascular dysfunction that is thought to predispose humans to the development of structural vascular changes that precede the development of atherosclerotic plaques. To test the effect of heavy-ion radiation on endothelium-dependent vasodilation, we used the same ApoE-/- mouse model in which we previously demonstrated the pro-atherogenic effect of 56Fe on plaque development. Ten week old male ApoE mice (an age at which there is little atherosclerotic plaque in the descending aorta) were exposed to 2.6 Gy 56Fe. The mice were then fed a normal diet and housed under standard conditions. At 4-5 weeks post-irradiation, aortic rings were isolated and endothelial-dependent relaxation was measured. Relaxation in response to acetylcholine was significantly impaired in irradiated mice compared to age-matched, un-irradiated mice. This decrease in vascular reactivity following 56Fe irradiation occurred eight weeks prior to the development of statistically significant exacerbation of aortic plaque formation and may contribute to the formation of later atherosclerotic lesions.

  9. A comparison of the effect of attention training and relaxation on responses to pain.

    PubMed

    Sharpe, L; Nicholson Perry, K; Rogers, P; Dear, B F; Nicholas, M K; Refshauge, K

    2010-09-01

    This study aimed to investigate the efficacy of an attention training technique (ATT) on pain ratings, threshold and tolerance during the cold pressor task. One hundred and three undergraduate students were randomly assigned to receive either threat-alleviating or threat-inducing information about the task. Participants were then re-randomized to receive either ATT or progressive muscle relaxation (PMR). Hence, the present study had a 2 (threat expectancy: high vs. low)x2 (training: ATT vs. PMR) design. Analyses confirmed that the threat manipulation was effective in increasing the harm associated with the task. ATT resulted in a relative reduction in hypervigilance to sensory pain words compared to PMR. ATT was also associated with a lower degree of focus on internal sensations, but not mindfulness or difficulty disengaging from pain words. Results showed that, relative to relaxation training, those receiving ATT reported pain less quickly than those receiving relaxation, although there were no differences between the training groups for tolerance or pain ratings. These results show that ATT changes the cognitive processes of internal/external focus and hypervigilance towards sensory pain words, but not difficulty disengaging or mindfulness. Although ATT changed threshold, the fact that neither pain ratings nor tolerance was affected suggests that a single, brief session of ATT may not be sufficient to affect broader change. Nonetheless, this study shows that ATT can change cognitive processes thought to be associated with heightened perception of pain and that this changes how quickly pain is registered and is therefore worthy of further investigation. Crown Copyright (c) 2010. Published by Elsevier B.V. All rights reserved.

  10. Enhancement effects of nicotine on neurogenic relaxation responses in the corpus cavernosum in rabbits: the role of nicotinic acetylcholine receptor subtypes.

    PubMed

    Ozturk Fincan, Gokce Sevim; Vural, Ismail Mert; Ercan, Zeynep Sevim; Sarioglu, Yusuf

    2010-02-10

    Nicotine acts as an agonist of nicotinic acetylcholine receptors, which belong to a superfamily of neurotransmitter-gated ion channels. We previously demonstrated that nicotine increases the electrical field stimulation (EFS)-evoked nitrergic relaxation responses via activation of nicotinic acetylcholine receptors. The aim of the present study is to investigate the subtypes of nicotinic acetylcholine receptors in rabbit corpus cavernosum. EFS-evoked relaxation responses were recorded from corpus cavernosum strips obtained from rabbits with an isometric force displacement transducers. Effects of nicotine on EFS-evoked relaxations were examined in pre-contracted tissues. Then the effect of nicotine on the EFS-evoked relaxations was examined in the presence of hexamethonium, dihydro-beta-erythroidine, mecamylamine or alpha-bungarotoxin. In our study, nicotine (3 x 10(-5), 10(-4)) transiently increased nitrergic relaxations induced by EFS in the rabbit isolated corpus cavernosum. While hexamethonium and mecamylamine near totally inhibited or abolished the neurorelaxation response to nicotine (3 x 10(-5)) on EFS, dihydro-beta-erythroidine and alpha-bungarotoxin partially inhibited these responses. These findings demonstrated that the alpha3-beta4, alpha4-beta2 and alpha7 subunits of nicotinic acetylcholine receptors play role on the nicotine-induced augmentation in EFS-evoked relaxation responses in rabbit corpus cavernosum. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  11. Effectiveness of the Relaxation Response-Based Group Intervention for Treating Depressed Chinese American Immigrants: A Pilot Study

    PubMed Central

    Yeung, Albert; Slipp, Lauren E.; Niles, Halsey; Jacquart, Jolene; Chow, Choi-Ling; Fava, Maurizio; Denninger, John W.; Benson, Herbert; Fricchione, Gregory L.

    2014-01-01

    Background: This study examined the feasibility, safety and efficacy of an 8-week Relaxation Response (RR)-based group. Methods: Twenty-two depressed Chinese American immigrants were recruited. Outcomes measures were response and remission rates, the Hamilton Rating Scale for Depression, Clinical Global Impressions Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, and the Multidimensional Scale of Perceived Social Support Scale. Results: Participants (N = 22) were 82% female, mean age was 53 (±12). After intervention, completers (N = 15) showed a 40% response rate and a 27% remission rate, and statistically significant improvement in most outcome measures. Discussion: The RR-based group is feasible and safe in treating Chinese American immigrants with depression. PMID:25198683

  12. Effect of dietary salt loading and high-calcium diet on vascular smooth muscle responses and endothelium function in rats.

    PubMed

    Adegunloye, B J; Sofola, O A

    1997-11-01

    1. The present study examined the effects of concurrent manipulation of dietary calcium and salt on contractile responses of vascular smooth muscle (VSM) and endothelial function of aortic rings from Sprague-Dawley rats. 2. Salt loading enhanced the contractile response of the aortic rings to noradrenaline (NA), an effect that was blunted by a high calcium intake. 3. Removal of the endothelium and incubation of aortic rings in physiological salt solution containing methylene blue increased the sensitivity of the rings to NA. 4. The increase in the sensitivity of aortic rings induced by endothelium removal was more pronounced in aortic rings from salt-loaded rats. 5. Acetylcholine caused similar degrees of relaxation in all experimental groups, but the relaxation to histamine was smaller (P < 0.05) in salt-loaded rats than in other groups of rats; however, after removal of the endothelium, the contractile response to histamine was higher in salt-loaded rats. 6. The results indicate that the hypersensitivity of isolated aortic rings to agonists, as observed in salt-loaded rats, is due to altered responses of the VSM and not as a result of changes in the endothelium. In addition, salt loading tends to increase the synthesis of endothelium-dependent relaxing factor. The ability of salt loading to enhance the contractile responses of VSM to agonists can be prevented by supplementing the diet with high calcium.

  13. Whole blood viscosity and erythrocyte deformability are related to endothelium-dependent vasodilation and coronary risk in the elderly. The prospective investigation of the vasculature in Uppsala seniors (PIVUS) study.

    PubMed

    Sandhagen, Bo; Lind, Lars

    2012-01-01

    It has previously been shown that a high hemoglobin value, a major determinant of whole blood viscosity (WBV), predicts cardiovascular events. One putative mechanism might be an impaired endothelial function. Erythrocyte deformability is another rheologic feature of the erythrocyte being of importance for the flow properties of the blood, especially in the capillaries. The present study evaluates the relationships between blood viscosity, erythrocyte deformability assessed as erythrocyte fluidity (EF), coronary risk and endothelial vasodilatory function. In the population-based PIVUS study (1016 subjects aged 70); endothelium-dependent vasodilation (EDV) was evaluated by the invasive forearm technique with acetylcholine given in the brachial artery and the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD). WBV, plasma viscosity (PV) and EF were measured in a random sample of 573 subjects. WBV and PV were positively and EF negatively related to Framingham risk score. EDV was inversely related to both whole blood and plasma viscosity. FMD was not related to any rheologic variable. In multiple regression analyses WBV and EF were significantly related to EDV independently of gender, hypertension, smoking, hypercholesterolemia, obesity and diabetes. Acetylcholine-induced vasodilation in the forearm, but not FMD, was negatively related to whole blood viscosity and positively related to EF independently of traditional risk factors in elderly subjects, indicating a pathophysiological link between impaired hemorheology and coronary risk.

  14. Structure-redox-relaxivity relationships for redox responsive manganese-based magnetic resonance imaging probes.

    PubMed

    Gale, Eric M; Mukherjee, Shreya; Liu, Cynthia; Loving, Galen S; Caravan, Peter

    2014-10-06

    A library of 10 Mn-containing complexes capable of switching reversibly between the Mn(II) and Mn(III) oxidation states was prepared and evaluated for potential usage as MRI reporters of tissue redox activity. We synthesized N-(2-hydroxybenzyl)-N,N',N'-ethylenediaminetriacetic acid (HBET) and N-(2-hydroxybenzyl-N,N',N'-trans-1,2-cyclohexylenediaminetriacetic acid (CyHBET) ligands functionalized (-H, -OMe, -NO2) at the 5-position of the aromatic ring. The Mn(II) complexes of all ligands and the Mn(III) complexes of the 5-H and 5-NO2 functionalized ligands were synthesized and isolated, but the Mn(III) complexes with the 5-OMe functionalized ligands were unstable. (1)H relaxivity of the 10 isolable complexes was measured at pH 7.4 and 37 °C, 1.4 T. Thermodynamic stability, pH-dependent complex speciation, hydration state, water exchange kinetics of the Mn(II) complexes, and pseudo-first order reduction kinetics of the Mn(III) complexes were studied using a combination of pH-potentiometry, UV-vis spectroscopy, and (1)H and (17)O NMR measurements. The effects of ligand structural and electronic modifications on the Mn(II/III) redox couple were studied by cyclic voltammetry. The Mn(II) complexes are potent relaxation agents as compared to the corresponding Mn(III) species with [Mn(II)(CyHBET)(H2O)](2-) exhibiting a 7.5-fold higher relaxivity (3.3 mM(-1) s(-1)) than the oxidized form (0.4 mM(-1) s(-1)). At pH 7.4, Mn(II) exists as a mixture of fully deprotonated (ML) and monoprotonated (HML) complexes and Mn(II) complex stability decreases as the ligands become more electron-releasing (pMn for 10 μM [Mn(II)(CyHBET-R')(H2O)](2-) decreases from 7.6 to 6.2 as R' goes from -NO2 to -OMe, respectively). HML speciation increases as the electron-releasing nature of the phenolato-O donor increases. The presence of a water coligand is maintained upon conversion from HML to ML, but the water exchange rate of ML is faster by up to 2 orders of magnitude (k(ex)(310) for H

  15. Relaxation oscillator-realized artificial electronic neurons, their responses, and noise

    NASA Astrophysics Data System (ADS)

    Lim, Hyungkwang; Ahn, Hyung-Woo; Kornijcuk, Vladimir; Kim, Guhyun; Seok, Jun Yeong; Kim, Inho; Hwang, Cheol Seong; Jeong, Doo Seok

    2016-05-01

    A proof-of-concept relaxation oscillator-based leaky integrate-and-fire (ROLIF) neuron circuit is realized by using an amorphous chalcogenide-based threshold switch and non-ideal operational amplifier (op-amp). The proposed ROLIF neuron offers biologically plausible features such as analog-type encoding, signal amplification, unidirectional synaptic transmission, and Poisson noise. The synaptic transmission between pre- and postsynaptic neurons is achieved through a passive synapse (simple resistor). The synaptic resistor coupled to the non-ideal op-amp realizes excitatory postsynaptic potential (EPSP) evolution that evokes postsynaptic neuron spiking. In an attempt to generalize our proposed model, we theoretically examine ROLIF neuron circuits adopting different non-ideal op-amps having different gains and slew rates. The simulation results indicate the importance of gain in postsynaptic neuron spiking, irrespective of the slew rate (as long as the rate exceeds a particular value), providing the basis for the ROLIF neuron circuit design. Eventually, the behavior of a postsynaptic neuron in connection to multiple presynaptic neurons via synapses is highlighted in terms of EPSP evolution amid simultaneously incident asynchronous presynaptic spikes, which in fact reveals an important role of the random noise in spatial integration.A proof-of-concept relaxation oscillator-based leaky integrate-and-fire (ROLIF) neuron circuit is realized by using an amorphous chalcogenide-based threshold switch and non-ideal operational amplifier (op-amp). The proposed ROLIF neuron offers biologically plausible features such as analog-type encoding, signal amplification, unidirectional synaptic transmission, and Poisson noise. The synaptic transmission between pre- and postsynaptic neurons is achieved through a passive synapse (simple resistor). The synaptic resistor coupled to the non-ideal op-amp realizes excitatory postsynaptic potential (EPSP) evolution that evokes postsynaptic

  16. A comparison of in vitro relaxant responses to ipratropium bromide, β-adrenoceptor agonists and theophylline in feline bronchial smooth muscle.

    PubMed

    Leemans, Jérôme; Kirschvink, Nathalie; Gustin, Pascal

    2012-07-01

    This study compares the potency and efficacy of different relaxant drugs including anticholinergic, β-adrenergic and methylxanthine agents on acetylcholine-contracted feline bronchi, and investigates the influence of the initial muscarinic-induced tone on bronchodilator response. Feline bronchi were removed from euthanased client-owned cats and were contracted with acetylcholine to cause either 40% or 80% of the acetylcholine maximal contraction. The efficacy and potency of bronchodilating drugs were obtained from cumulative dose-response curves with efficacy (E(max)) as the maximal relaxant response and potency (-logEC(50)) as the logarithm of the concentration of drug inducing 50% of maximal relaxation. Under low contractile tone (40%), all bronchodilators relaxed feline bronchi in a concentration-dependent manner with the following rank order of potency: formoterol>ipratropium bromide>fenoterol>isoprenaline>salbutamol≥salmeterol>theophylline. E(max) values ranged from 80% to 100% depending on the tested drug. Constriction of feline bronchi with high-dose acetylcholine (80%) caused a rightward and downward shift of the β(2)-mimetic dose-response curves. Significant decreases in -logEC(50) and E(max) values were reported for salbutamol, formoterol and salmeterol. This study provides evidence that existing classes of bronchodilators produce effective relaxation of acetylcholine-contracted feline bronchi and that airway responsiveness to β(2)-stimulants is dependent on the magnitude of the initial muscarinic-induced tone. The clinical relevance of these in vitro findings has yet to be explored in clinical trials.

  17. Chuanxiongzine relaxes isolated corpus cavernosum strips and raises intracavernous pressure in rabbits

    PubMed Central

    Xiao, H-J; Wang, T; Chen, J; Fan, L-C; Yin, C-P; Liu, J-H; Gao, X

    2009-01-01

    It has been shown that there are many Chinese traditional herbals that can enhance sexual activity. Chuanxiongzine is a vasoactive ingredient that has been isolated and purified from Ligusticum chuanxiong Hort. In previous studies, it has been found that chuanxiongzine was effective in relaxing rabbit corpus cavernosum smooth muscle. We determined the effects of chuanxiongzine on relaxation of isolated corpus cavernosum strips in vitro and on increase of intracavernous pressure (ICP) in vivo in rabbits. Chuanxiongzine caused a concentration-dependent relaxation of phenylephrine precontracted isolated corpus cavernosum strips (EC50 1.58 × 10−4 mol l−1), which were endothelium independent and NO independent. However, the guanylyl cyclase inhibitor 1-H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one significantly shifted the chuanxiongzine concentration–response relationship to the right. Although there was no significant difference in the level of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) in isolated corpus cavernosum strips treated with chuanxiongzine or vehicle, chuanxiongzine caused a significant rise in the level of cGMP and cAMP in isolated corpus cavernosum strips pretreated with the activator of adenylyl cyclase forskolin and the source of NO sodium nitroprusside. In an in vivo study, chuanxiongzine dose-dependently raised ICP after the intracavernous injection of its cumulative doses (0.5, 1, 2 and 5 mg kg−1). The ICP increased from baseline to 19.1±3.7, 24.8±2.1, 30.2±4.8 and 39.7±6.1 mm Hg, respectively, and the duration of tumescence ranged from 8.5±2.8 to 22.9±7.3 min. Our results show that chuanxiongzine can relax isolated corpus cavernosum strips of rabbits in vitro and increase ICP of rabbits in vivo, which is neither endothelium dependent nor NO dependent, but may be partly mediated by the inhibition of cAMP phosphodiesterase or cGMP phosphodiesterase. PMID:19940852

  18. MT2 receptors mediate the inhibitory effects of melatonin on nitric oxide-induced relaxation of porcine isolated coronary arteries.

    PubMed

    Tunstall, Radhika R; Shukla, Praveen; Grazul-Bilska, Anna; Sun, Chengwen; O'Rourke, Stephen T

    2011-01-01

    Previous studies from our laboratory demonstrated that melatonin inhibits nitric oxide (NO)-induced relaxation in porcine coronary arteries. The present study was designed to further characterize the mechanisms underlying this inhibitory effect of melatonin. Western immunoblot studies identified the presence of melatonin type 2 (MT(2)) receptors, but not MT(1) or MT(3) receptors, in porcine coronary arteries. Immunohistochemical analysis revealed that MT(2) receptors colocalized with α-actin in the smooth muscle cell layer. In coronary arterial rings suspended in organ chambers for isometric tension recording, melatonin (10(-7) M) inhibited relaxations induced by the exogenous NO donor sodium nitroprusside (SNP; 10(-9) to 10(-5) M) and by the α(2)-adrenoceptor agonist 5-bromo-6-[2-imidazolin-2-yl-amino]-quinoxaline (UK14,304; 10(-9) to 10(-5) M), an endothelium-dependent vasodilator. The inhibitory effect of melatonin on SNP- and UK14,304-induced relaxations was abolished in the presence of the selective MT(2) receptor antagonists 4-phenyl-2-propionamidotetralin (4P-PDOT; 10(-7) M) and luzindole (10(-7) M). In contrast to melatonin, the selective MT(3) receptor agonist 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT; 10(-7) M) had no effect on the concentration-response curves to either SNP or UK14,304. Melatonin (10(-7) M) had no effect on coronary artery relaxation induced by 8-bromoguanosine 3',5'-cyclic monophosphate, but it significantly attenuated the increase in intracellular cyclic GMP levels in response to SNP (10(-5) M). This effect of melatonin was abolished in the presence of 4P-PDOT (10(-7) M). Taken together, these data support the view that melatonin acts on MT(2) receptors in coronary vascular smooth muscle cells to inhibit NO-induced increases in cyclic GMP and coronary arterial relaxation, thus demonstrating a novel function for MT(2) receptors in the vasculature.

  19. Contribution of material properties of cellular components on the viscoelastic, stress-relaxation response of a cell during AFM indentation

    NASA Astrophysics Data System (ADS)

    Unnikrishnan, Ginu U.; Unnikrishnan, Vinu U.; Reddy, J. N.

    2016-05-01

    The close relationship between the mechanical properties of biological cells, namely, elasticity, viscosity, and the state of its disease condition has been widely investigated using atomic force microscopy (AFM). In this study, computational simulation of the AFM indentation is carried out using a finite element (FE) model of an adherent cell. A parametric evaluation of the material properties of the cellular components on the viscoelastic, stress-relaxation response during AFM indentation is performed. In addition, the loading rate, the size of the nucleus, and the geometry of the cell are varied. From the present study, it is found that when comparing the material properties derived from experimental force-deflection curves, the influence of loading rates should be accommodated. It also provides a framework that can quantify the variation of the mechanical property with various stages of malignancy of the cancer cell, a potential procedure for cancer diagnosis.

  20. A Comparison of Relaxation Strategies.

    ERIC Educational Resources Information Center

    Matthews, Doris B.

    Some researchers argue that all relaxation techniques produce a single relaxation response while others support a specific-effects hypothesis which suggests that progressive relaxation affects the musculoskeletal system and that guided imagery affects cognitive changes. Autogenics is considered a technique which is both somatic and cognitive. This…

  1. Functional interactions in smooth muscle: kinetic characterization of the relaxation and desensitization responses to a beta adrenergic agonist in the rabbit aorta.

    PubMed

    Keitz, S A; Osman, R; Clarke, W P; Goldfarb, J; Maayani, S

    1990-11-01

    Vascular smooth muscle tone is continuously modulated in vivo by the functional interaction of a variety of vasoconstrictor and vasodilator stimuli. Endogenous substances such as epinephrine simultaneously activate alpha adrenergic receptors that elicit muscle contraction and beta adrenergic receptors that relax the muscle. This study characterizes the beta adrenergic response in the isolated rabbit aorta precontracted with 1 microM phenylephrine. The beta adrenergic agonist isoproterenol (0.03-10 microM) produces a biphasic response that is composed of a rapid relaxation followed by a slower regaining of tension, which is identified as desensitization. An exploratory kinetic model that describes both the relaxation and the desensitization as first-order processes provides a good fit to the experimental data. The parameters used to describe the isoproterenol response are: 1) the observed rate constant for relaxation and its magnitude (krel and R, respectively), 2) the observed rate constant for desensitization and its magnitude (kdes and D, respectively) and 3) the observed delay in the onset of the desensitization response (td). Both the krel and the fractional relaxation were dependent on concentration of isoproterenol in a saturable manner (EC50 = 0.017 and 0.067 microM, respectively). No concentration dependence was observed for kdes, fractional desensitization and td (the average values +/- S.E.M. of these parameters are (4.7 +/- 0.2). 10(-3) sec-1, 0.83 +/- 0.02 and 191 +/- 6 sec, respectively). This work demonstrates that a kinetic approach is necessary to characterize the desensitization response and is also very useful in characterizing the kinetic and steady-state parameters of the relaxation response.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Relaxed heaps

    SciTech Connect

    Driscoll, J.R. ); Gabow, H.N.; Shrairman, R. ); Tarjan, R.E. )

    1988-11-01

    The relaxed heap is a priority queue data structure that achieves the same amortized time bounds as the Fibonacci heap - a sequence of m decrease key and n delete min operations takes time O(m + n log n). A variant of relaxed heaps achieves similar bounds in the worst case - O(1) time for decrease key and O(log n) for delete min. Relaxed heaps give a processor-efficient parallel implementation of Dijkstra's shortest path algorithm, and hence other algorithms in network optimization. A relaxed heap is a type of binomial queue that allows heap order to be violated.

  3. Propofol increases vascular relaxation in aging rats chronically treated with the angiotensin-converting enzyme inhibitor captopril.

    PubMed

    Gragasin, Ferrante S; Bourque, Stephane L; Davidge, Sandra T

    2013-04-01

    = 0.22). l-NAME-dependent inhibition of MCh relaxation, however, was greater in arteries from control compared with captopril-treated rats (P = 0.0077). However, propofol increased the proportion of NO-dependent vasodilation to MCh similarly in both groups. This suggests that other vasodilatory pathways are involved in the differential response to MCh in the presence of propofol in captopril-treated rats. Our results show that mesenteric arterial relaxation in response to propofol, both by direct stimulation and through modulation of endothelium-dependent mechanisms, is, in part, NO-dependent. In captopril-treated rats, propofol further increased arterial relaxation through a non-NO-dependent vasodilating pathway (e.g., endothelium-derived hyperpolarizing factor), which may account for enhanced vasodilation during propofol exposure in patients treated with ACE inhibitors.

  4. Tracheal epithelium cell volume responses to hyperosmolar, isosmolar and hypoosmolar solutions: relation to epithelium-derived relaxing factor (EpDRF) effects

    PubMed Central

    Fedan, Jeffrey S.; Thompson, Janet A.; Ismailoglu, U. Burcin; Jing, Yi

    2013-01-01

    In asthmatic patients, inhalation of hyperosmolar saline or D-mannitol (D-M) elicits bronchoconstriction, but in healthy subjects exercise causes bronchodilation. Hyperventilation causes drying of airway surface liquid (ASL) and increases its osmolarity. Hyperosmolar challenge of airway epithelium releases epithelium-derived relaxing factor (EpDRF), which relaxes the airway smooth muscle. This pathway could be involved in exercise-induced bronchodilation. Little is known of ASL hyperosmolarity effects on epithelial function. We investigated the effects of osmolar challenge maneuvers on dispersed and adherent guinea-pig tracheal epithelial cells to examine the hypothesis that EpDRF-mediated relaxation is associated with epithelial cell shrinkage. Enzymatically-dispersed cells shrank when challenged with ≥10 mOsM added D-M, urea or NaCl with a concentration-dependence that mimics relaxation of the of isolated perfused tracheas (IPT). Cells shrank when incubated in isosmolar N-methyl-D-glucamine (NMDG) chloride, Na gluconate (Glu), NMDG-Glu, K-Glu and K2SO4, and swelled in isosmolar KBr and KCl. However, isosmolar challenge is not a strong stimulus of relaxation in IPTs. In previous studies amiloride and 4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid (DIDS) inhibited relaxation of IPT to hyperosmolar challenge, but had little effect on shrinkage of dispersed cells. Confocal microscopy in tracheal segments showed that adherent epithelium is refractory to low hyperosmolar concentrations that induce dispersed cell shrinkage and relaxation of IPT. Except for gadolinium and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), actin and microtubule inhibitors and membrane permeabilizing agents did not affect on ion transport by adherent epithelium or shrinkage responses of dispersed cells. Our studies dissociate relaxation of IPT from cell shrinkage after hyperosmolar challenge of airway epithelium. PMID:24130533

  5. Relative roles of nitric oxide and cyclo-oxygenase and lipoxygenase products of arachidonic acid in the contractile responses of rat renal arcuate arteries.

    PubMed Central

    Wu, X. C.; Richards, N. T.; Michael, J.; Johns, E.

    1994-01-01

    1. We have examined the effects of inhibition of nitric oxide synthase, cyclo-oxygenase and lipoxygenase on the responses of renal arcuate arteries of Wistar rats, with and without endothelium, to noradrenaline, potassium chloride, endothelin-1, acetylcholine and sodium nitroprusside. 2. Noradrenaline, potassium chloride and endothelin-1 caused concentration-dependent contraction of the vessels. Indomethacin (14 microM) attenuated the contractile response to noradrenaline and to potassium chloride. The inhibitory effect of indomethacin persisted following endothelial removal. 3. Acetylcholine produced concentration-dependent relaxation of the vessels which was potentiated by indomethacin (14 microM). 4. NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) did not affect the contractile response to either noradrenaline or potassium chloride but abolished relaxation to acetylcholine. In addition, L-NAME abolished the affects of indomethacin on acetylcholine-induced relaxation and noradrenaline- and potassium chloride-induced contraction. 5. BWC755C attenuated noradrenaline and potassium chloride-induced contraction. This effect persisted in the presence of indomethacin. 6. In vessels pretreated with CHAPS, BW755C inhibited both noradrenaline and potassium chloride-induced contraction. In these vessels BW755C had no additional inhibitory effect to indomethacin on noradrenaline- and potassium-induced contraction. 7. Inhibition of nitric oxide synthase with L-NAME (100 microM) attenuated the effect of BW755C on noradrenaline- and potassium-induced contraction. 8. BW755C alone did not affect endothelium-dependent relaxation as assessed by the response to acetylcholine. However, in the presence of indomethacin, BW755C inhibited acetylcholine-induced relaxation. 9. BW755C did not affect endothelium-independent relaxation as assessed by the response to sodium nitroprusside in vessels with or without endothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8075854

  6. Physiological Predictors of Response to Exposure, Relaxation, and Rescripting Therapy for Chronic Nightmares in a Randomized Clinical Trial

    PubMed Central

    Davis, Joanne L.; Rhudy, Jamie L.; Pruiksma, Kristi E.; Byrd, Patricia; Williams, Amy E.; McCabe, Klanci M.; Bartley, Emily J.

    2011-01-01

    Study Objectives: Evidence supports the use of cognitive behavioral therapies for nightmares in trauma-exposed individuals. This randomized clinical trial replicated a study of exposure, relaxation, and rescripting therapy(ERRT) and extended prior research by including broad measures of mental health difficulties, self-reported physical health problems, and quality of life. Additionally, physiological correlates of treatment-related change assessed from a script-driven imagery paradigm were examined. Methods: Forty-seven individuals were randomized to treatment or waitlist control. Results: The treatment group demonstrated improvements relative to the control group at the one-week post-treatment assessment. At the 6-month follow-up assessment, significant improvements were found for frequency and severity of nightmares, posttraumatic stress disorder symptoms, depression, sleep quality and quantity, physical health symptoms, anger, dissociation, and tension reduction behaviors. Participants also reported improved quality of life. Treatment-related decreases in heart rate to nightmare imagery were correlated with improvements in sleep quality and quantity; treatment-related decreases in skin conductance to nightmare imagery were correlated with improvements in nightmare severity, posttraumatic stress disorder symptom severity, sleep quality, and fear of sleep; and treatment-related decreases in corrugator activity to nightmare imagery were correlated with improved physical health. Conclusions: Findings provide additional support for the use of ERRT in treating nightmares and related difficulties and improving sleep. Citation: Davis JL; Rhudy JL; Pruiksma KE; Byrd P; Williams AE; McCabe KM; Bartley EJ. Physiological predictors of response to exposure, relaxation, and rescripting therapy for chronic nightmares in a randomized clinical trial. J Clin Sleep Med 2011;7(6):622-631. PMID:22171201

  7. Normal tissue quantitative T1 and T2* MRI relaxation time responses to hypercapnic and hyperoxic gases.

    PubMed

    Winter, Jeff D; Estrada, Marvin; Cheng, Hai-Ling Margaret

    2011-09-01

    Longitudinal (T(1)) and effective transverse (T(2)*) magnetic resonance (MR) relaxation times provide noninvasive measures of tissue oxygenation. The objective for this study was to quantify independent effects of inhaled O(2) and CO(2) on normal tissue T(1) and T(2)* in rabbit liver, kidney, and paraspinal muscle. Three gas challenges (100% O(2), 10% CO(2) [balance air], and carbogen [90% O(2) + 10% CO(2)]) were delivered to the rabbits in random order to isolate the effects of inspired O(2) and CO(2). During each challenge, quantitative T(1) and T(2)* maps were collected on a 1.5 Tesla MR imaging. Mean changes in T(1) (ΔT(1)) and T(2)* (ΔT(2)*) were calculated from regions of interest in each organ. Greatest ΔT(1) and ΔT(2)* changes were observed in liver for 10% CO(2) and in kidney for 100% O(2). ΔT(1) and ΔT(2)* generally followed predicted patterns when transitioning from air breathing: lower T(1)/higher T(2)* with inspired O(2), higher T(1)/lower T(2)* with inspired CO(2), and variable T(1)/T(2)* changes in the presence of both (ie, carbogen). New observations also emerged: 1) between-gas-challenge transitions revealed the greatest significance in ΔT(2)* for the liver and kidney resulting from the isolation of independent O(2) and CO(2) effects; 2) ΔT(2)* provided the best sensitivity and detected both tissue oxygenation and blood volume modulation; and 3) ΔT(1) sensitivity was restricted mainly to tissue oxygenation in the absence of counteracting vasodilatation. Robust use of MR relaxation times as noninvasive biomarkers requires an understanding of their relative sensitivity to organ-specific physiological responses. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

  8. Mas receptor overexpression increased Ang-(1-7) relaxation response in renovascular hypertensive rat carotid.

    PubMed

    Olivon, V C; Aires, R D; Santiago, L B; Ramalho, L Z N; Cortes, S F; Lemos, V S

    2015-09-01

    Renin-angiotensin system (RAS) is an important factor in the pathophysiology of hypertension. Mas receptor, Angiotensin-(1-7) [Ang-(1-7)]-activated receptor, is an important RAS component and exerts protective effects in the vasculature. Ang-(1-7) vascular effects and Mas receptor expression in carotid from renovascular hypertensive (2K-1C) rats is not clear. In the present study we investigated Mas receptor vasodilator response activated by Ang-(1-7) in the carotid rings from sham and 2K-1C rats. Changes in isometric tension were recorded on organ chamber. Mas receptors expression was investigated in carotid by Western blot. Nitric oxide production was evaluated by 2,3-diaminonaphthalene (DAN) and eNOS expression and activity by immunofluoresce and western blot, respectively. Ang-(1-7) induced concentration-dependent vasodilator effect in carotid rings from sham and 2K-1C, which the hypertension increased vasodilatation response. In the 2K-1C carotid rings, A-779 (Mas receptor antagonist) reduced but not abolish the vasodilator effect of Ang-(1-7). Corroborating, Mas receptor protein expression was significantly increased in the 2K-1C rats. L-NAME and ibuprofen decreased Ang-(1-7) vasodilator response and L-NAME plus ibuprofen practically abolish the remaining vasodilatation response. Nitric oxide production is increased due increased of eNOS expression and pSer(1177) activity. Our results demonstrated that renovascular hypertension increased Mas receptors expression and nitric oxide production in the rats carotid which, consequently increased Ang-(1-7)-vasorelaxant response. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Relaxation effect of abacavir on rat basilar arteries.

    PubMed

    Li, Rachel Wai Sum; Yang, Cui; Chan, Shun Wan; Hoi, Maggie Pui Man; Lee, Simon Ming Yuen; Kwan, Yiu Wa; Leung, George Pak Heng

    2015-01-01

    The use of abacavir has been linked with increased cardiovascular risk in patients with human immunodeficiency virus infection; however, the mechanism involved remains unclear. We hypothesize that abacavir may impair endothelial function. In addition, based on the structural similarity between abacavir and adenosine, we propose that abacavir may affect vascular contractility through endogenous adenosine release or adenosine receptors in blood vessels. The relaxation effect of abacavir on rat basilar arteries was studied using the myograph technique. Cyclic GMP and AMP levels were measured by immunoassay. The effects of abacavir on nucleoside transporters were studied using radiolabeled nucleoside uptake experiments. Ecto-5' nucleotidase activity was determined by measuring the generation of inorganic phosphate using adenosine monophosphate as the substrate. Abacavir induced the relaxation of rat basilar arteries in a concentration-dependent manner. This relaxation was abolished when endothelium was removed. In addition, the relaxation was diminished by the nitric oxide synthase inhibitor, L-NAME, the guanylyl cyclase inhibitor, ODQ, and the protein kinase G inhibitor, KT5820. Abacavir also increased the cGMP level in rat basilar arteries. Abacavir-induced relaxation was also abolished by adenosine A2 receptor blockers. However, abacavir had no effect on ecto-5' nucleotidase and nucleoside transporters. Short-term and long-term treatment of abacavir did not affect acetylcholine-induced relaxation in rat basilar arteries. Abacavir induces acute endothelium-dependent relaxation of rat basilar arteries, probably through the activation of adenosine A2 receptors in endothelial cells, which subsequently leads to the release of nitric oxide, resulting in activation of the cyclic guanosine monophosphate/protein kinase G-dependent pathway in vascular smooth muscle cells. It is speculated that abacavir-induced cardiovascular risk may not be related to endothelial dysfunction

  10. Relaxation Effect of Abacavir on Rat Basilar Arteries

    PubMed Central

    Li, Rachel Wai Sum; Yang, Cui; Chan, Shun Wan; Hoi, Maggie Pui Man; Lee, Simon Ming Yuen; Kwan, Yiu Wa; Leung, George Pak Heng

    2015-01-01

    Background The use of abacavir has been linked with increased cardiovascular risk in patients with human immunodeficiency virus infection; however, the mechanism involved remains unclear. We hypothesize that abacavir may impair endothelial function. In addition, based on the structural similarity between abacavir and adenosine, we propose that abacavir may affect vascular contractility through endogenous adenosine release or adenosine receptors in blood vessels. Methods The relaxation effect of abacavir on rat basilar arteries was studied using the myograph technique. Cyclic GMP and AMP levels were measured by immunoassay. The effects of abacavir on nucleoside transporters were studied using radiolabeled nucleoside uptake experiments. Ecto-5′ nucleotidase activity was determined by measuring the generation of inorganic phosphate using adenosine monophosphate as the substrate. Results Abacavir induced the relaxation of rat basilar arteries in a concentration-dependent manner. This relaxation was abolished when endothelium was removed. In addition, the relaxation was diminished by the nitric oxide synthase inhibitor, L-NAME, the guanylyl cyclase inhibitor, ODQ, and the protein kinase G inhibitor, KT5820. Abacavir also increased the cGMP level in rat basilar arteries. Abacavir-induced relaxation was also abolished by adenosine A2 receptor blockers. However, abacavir had no effect on ecto-5’ nucleotidase and nucleoside transporters. Short-term and long-term treatment of abacavir did not affect acetylcholine-induced relaxation in rat basilar arteries. Conclusion Abacavir induces acute endothelium-dependent relaxation of rat basilar arteries, probably through the activation of adenosine A2 receptors in endothelial cells, which subsequently leads to the release of nitric oxide, resulting in activation of the cyclic guanosine monophosphate/protein kinase G-dependent pathway in vascular smooth muscle cells. It is speculated that abacavir-induced cardiovascular risk may

  11. Microwave responses and general model of nanotetraneedle ZnO: Integration of interface scattering, microcurrent, dielectric relaxation, and microantenna

    NASA Astrophysics Data System (ADS)

    Fang, Xiao-Yong; Cao, Mao-Sheng; Shi, Xiao-Ling; Hou, Zhi-Ling; Song, Wei-Li; Yuan, Jie

    2010-03-01

    Based on the unique geometrical structure of nanotetra-ZnO needle (T-ZnON), we investigate the microwave responses of T-ZnON, including interface scattering, microcurrent attenuation, microantenna radiation, and dielectric relaxation, and build an energy attenuation model. The associated quantitative formula is deduced for calculating the microwave absorption properties of T-ZnON/SiO2 nanocomposite (T-ZnON/SiO2) in the range 8-14 GHz according to the present energy attenuation model. Very good agreement between the calculated and experimental results is obtained in a wide frequency range. The maximum deviation less than 0.5 dB in the range 8-14 GHz is obtained. Using the aforementioned model, we analyze the contribution of microwave responses to the energy attenuation in the frequency range 2-18 GHz, and the results reveal that interface scattering and microcurrent attenuation make the contribution most important. In addition, we calculate the effects of the volume fraction, conductivity, permittivity, needle length of T-ZnON, and thickness of T-ZnON/SiO2 on the reflectivity. The results show that the microwave absorption is evidently dependent on these effect factors, and the optimal microwave absorption band and the strongest microwave absorption peak of T-ZnON/SiO2 would appear when these physical parameters are changed.

  12. Impedance response and dielectric relaxation in co-precipitation derived ferrite (Ni,Zn)Fe2O4 ceramics

    NASA Astrophysics Data System (ADS)

    Chen, D. G.; Tang, X. G.; Liu, Q. X.; Jiang, Y. P.; Ma, C. B.; Li, R.

    2013-06-01

    Dielectric spectra and magnetization hysteresis loops were used to investigate the grain size effect with temperature on the electrical and magnetic response of co-precipitation derived spinel (Ni0.5Zn0.5)Fe2O4 (NZFO) ceramics. Remarkable dielectric relaxation phenomena of non-Debye type have been observed in each NZFO ceramics as confirmed by two kinds of Cole-Cole plots of the 1100 °C sintered samples, mainly due to the electron-hopping mechanism between n-type and p-type carriers and interfacial ion effect when applied an increase of temperature. The high and low response of grain and grain-boundary regions were determined by modeling the impedance experimental results on two equivalent RC circuits taking into account grain deep trap states. By employing the modified Arrhenius equation, activation energy values of different sintering temperatures were calculated and analyzed in combination with oxygen vacancy. In addition, the magnetization of various sintering temperature samples is dominated by cation distribution and surface effect in different particle ranges.

  13. Flexion Relaxation Ratio Not Responsive to Acutely Induced Low Back Pain from a Delayed Onset Muscle Soreness Protocol

    PubMed Central

    Horn, Maggie E.; Bishop, Mark D.

    2013-01-01

    Background. The flexion relaxation ratio (FRR) has been suggested as a measure of muscular performance in patients with low back pain (LBP). The purpose of this study was to investigate whether the FRR was responsive to acute LBP produced from a delayed onset muscle soreness (DOMS) protocol. Methods. Fifty-one pain-free volunteers performed DOMS to induce LBP. Current pain intensity, trunk flexion range of motion (ROM), and passive straight leg raise (SLR) were measured at baseline, 24 and 48 hours after DOMS. Participants were categorized into pain groups based on reported current pain intensity. Changes in FRR, trunk flexion ROM, and SLR ROM were examined using two-way repeated measures analysis of variance. Results. Pain group was not found to have a significant effect on FRR (F1,29 = 0.054, P = 0.818), nor were there any two-way interactions for changes in FRR. The pain group had decreased trunk flexion ROM compared to the minimal pain group (F1,38 = 7.21, P = 0.011), but no decreases in SLR ROM (F1,38 = 3.51, P = 0.057) over time. Interpretation. There were no differences in FRR based on reported pain intensity of LBP from a DOMS protocol. The responsiveness of FRR might be limited in patients with acute onset LBP of muscular origin. PMID:27335879

  14. Relation of improvement in endothelium-dependent flow-mediated vasodilation after rosiglitazone to changes in asymmetric dimethylarginine, endothelin-1, and C-reactive protein in nondiabetic patients with the metabolic syndrome.

    PubMed

    Wang, Tzung-Dau; Chen, Wen-Jone; Cheng, Wern-Cherng; Lin, Jong-Wei; Chen, Ming-Fong; Lee, Yuan-Teh

    2006-10-15

    The mechanisms by which thiazolidinediones exert beneficial effects on the endothelium are still not clear. We examined the effects of rosiglitazone on the plasma markers of metabolic control (glucose, insulin, adiponectin, resistin, and lipid profiles), markers of inflammation (high-sensitivity C-reactive protein [CRP], interleukin-6, soluble CD40 ligand, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1), and markers of vasoreactivity (asymmetric dimethylarginine [ADMA] and endothelin-1) and analyzed the relations between changes in endothelium-dependent flow-mediated dilation of the brachial artery and changes in these markers to elucidate their roles in mediating the vascular protective effects of rosiglitazone. Of 70 nondiabetic patients who met a modified National Cholesterol Education Program definition of the metabolic syndrome, 35 were randomized to receive rosiglitazone (4 mg/day) and 35 to receive placebo for 8 weeks. At study end, treatment with rosiglitazone had significantly reduced plasma insulin (-25%, p = 0.004) and resistin (-16%, p <0.001), increased adiponectin (164%, p <0.001), low-density lipoprotein cholesterol (16%, p = 0.005), and apolipoprotein-B (14%, p = 0.003), and decreased CRP (-30%, p = 0.005), soluble CD40 ligand (-20%, p = 0.014), ADMA (-16%, p <0.001), and endothelin-1 (-11%, p <0.001) concentrations and systolic and diastolic blood pressures. Rosiglitazone treatment significantly improved flow-mediated dilation (p <0.001) and nitroglycerin-induced vasodilation (p = 0.001) of the right brachial artery. On multivariate analysis, changes in ADMA, endothelin-1, and CRP were independent predictors of improved endothelial reactivity with rosiglitazone. In conclusion, we have, for the first time, demonstrated the independent associations between the improvement in flow-mediated dilation and reductions in ADMA, endothelin-1, and CRP after 8 weeks of treatment with rosiglitazone in nondiabetic patients with the

  15. Does psychological testing help to predict the response to acupuncture or massage/relaxation therapy in patients presenting to a general neurology clinic with headache?

    PubMed

    Wylie, K R; Jackson, C; Crawford, P M

    1997-06-01

    Patients with chronic headache were offered treatment by acupuncture or massage with relaxation instead of a change in their prescribed medication. They were randomly allocated to either treatment. There was a significant improvement in pain ratings with both treatment types. Specifically a greater effect was seen in migraine patients treated by massage with relaxation when compared to acupuncture. No psychological factors were found to predict response to either treatment. At the end of the study, 13% of patients were significantly more worried that there may be a more serious cause underlying their headache despite reassurance and an improvement in their headache scores.

  16. Effect of trandolapril on vascular responsiveness in cholesterol-fed rabbit-isolated arteries.

    PubMed

    Sanz, M; Ganado, P; Ruiz, E; Tejerina, T

    2000-06-02

    According to the World Health Organisation, cardiovascular disorders are one of the main causes of morbi/mortality in the western world. The effect of trandolapril (0.3 mg kg(-1) day(-1)), a non-sulphydryl angiotensin-converting enzyme (ACE) inhibitor, on the vascular responsiveness in aorta isolated from hypercholesterolemic rabbits was examined. Three groups of rabbits (n=30) were used: Group 0 (control group); Group 1 (hypercholesterolemic group, 0.5% (wt/wt) cholesterol-enriched diet) and Group 2 (hypercholesterolemic+trandolapril 0.3 mg kg(-1) day(-1)). After 18 weeks of treatment, the rabbits were killed and the thoracic aorta, proximal coronary and mesenteric (5th branch) arteries were isolated, cleaned off and mounted in an organ bath. Trandolapril had no significant effect on plasma cholesterol, high density lipoprotein (HDL) or low density lipoprotein (LDL). Despite the lack of effect of the drug on the above-mentioned parameters, treatment with trandolapril improved endothelium-dependent relaxation induced by acetylcholine in aortic and mesenteric rings from hypercholesterolemic rabbits treated with trandolapril. The relaxation induced by 10(-5) M acetylcholine were 65.0+/-4.0%; 24. 0+/-9.4% (P<0.01, n=10) and 51.3+/-7.0% (P<0.01, n=10) in aortic rings from Groups 0, 1 and 2, respectively, and 50.0+/-12.0%; 10. 1+/-10.0% (P<0.01, n=10); 61.0+/-9.7% (P<0.01, n=10) in small mesenteric rings from Groups 0, 1 and 2, respectively. In addition, trandolapril treatment improved the increase in serotonin-induced contraction in proximal coronary arteries with respect to the hypercholesterolemic group. On the other hand, we did not find any differences among the group in endothelium-independent relaxation induced by sodium nitroprusside. These results provide evidence that trandolapril restores endothelium-dependent relaxation in hypercholesterolemic rabbit-isolated arteries. These data suggest that trandolapril might have beneficial action in the prevention of

  17. Radix angelica elicits both nitric oxide-dependent and calcium influx-mediated relaxation in rat aorta.

    PubMed

    Rhyu, Mee-Ra; Kim, Jung-Hyun; Kim, Eun-Young

    2005-07-01

    This study examined the vascular relaxation produced by Radix Angelica (AG; Dong Quai) and its possible mechanisms in isolated rat aortic rings precontracted with norepinephrine. The butanolic fraction (AgBt) of the crude extract of AG causes gradual endothelium-independent relaxation, which was unaffected by five different potassium channel inhibitors. AgBt attenuated the CaCl2-induced vasoconstriction in high-potassium depolarized medium; this required less than one-tenth the concentration needed to elicit vascular relaxation. An aqueous fraction (AgDw) of the crude extract induced transient acute relaxation, which was virtually abolished by endothelial ablation and pretreatment with L-NNA. L-Arginine fully reversed the action of L-NNA. Methylene blue and atropine significantly attenuated the relaxation, but indomethacin did not. Ferulic acid, the main active component in AG, relaxed both endothelium-intact and -denuded rings, while L-NNA, methylene blue, or atropine did not modify the relaxation. Ferulic acid also did not attenuate the CaCl2-induced contraction in high-potassium depolarized medium. In conclusion, Radix Angelica leads to both endothelium-dependent and -independent relaxation of isolated rat aorta. Increased formation of NO might contribute to the endothelium-mediated relaxation, while inhibition of the calcium influx might be an important mechanism in direct smooth muscle relaxation. A substance other than ferulic acid might create these effects.

  18. Effects of endopeptidase inhibition on the relaxation response of isolated human penile erectile tissue to vasoactive peptides.

    PubMed

    Rahardjo, H E; Reichelt, K; Sonnenberg, J E; Sohn, M; Kuczyk, M A; Ückert, S

    2016-12-01

    Peptides, such as CNP, CGRP and VIP, are involved in the function of male penile erectile tissue. Tissue levels of said peptides are controlled by the endopeptidase enzymes. Theoretically, the inhibition of the degradation of CNP, CGRP and/or VIP should result in an enhancement in penile smooth muscle relaxation. The effects were investigated of CNP or VIP (0.1 nm-1 μm), without and following pre-exposure of the tissue to a threshold concentration of the endopeptidase inhibitor KC 12615 (10 μm, for 20 min), on the reversion of tension induced by means of electrical field stimulation. Drug effects on the production of cyclic AMP/GMP were also evaluated. Neither KC 12615, CNP and VIP nor the combination of CNP plus KC 12615 or VIP plus KC 12615 increased the response of the tissue to EFS. While no effects were observed of a pre-exposure of the tissue to KC 12615 on the production of cyclic AMP in the presence of VIP, an enhancement was registered in the accumulation of cyclic AMP in the presence of CNP plus KC 12615. Further studies are indicated to investigate whether endopeptidase inhibitors might tend to be more effective in tissues affected by a decreased local production of vasoactive peptides. © 2016 Blackwell Verlag GmbH.

  19. Teacher-led relaxation response curriculum in an urban high school: impact on student behavioral health and classroom environment.

    PubMed

    Wilson, H Kent; Scult, Matthew; Wilcher, Marilyn; Chudnofsky, Rana; Malloy, Laura; Drewel, Emily; Riklin, Eric; Saul, Southey; Fricchione, Gregory L; Benson, Herbert; Denninger, John W

    2015-01-01

    Recent data suggest that severe stress during the adolescent period is becoming a problem of epidemic proportions. Elicitation of the relaxation response (RR) has been shown to be effective in treating anxiety, reducing stress, and increasing positive health behaviors. The research team's objective was to assess the impact of an RR-based curriculum, led by teachers, on the psychological status and health management behaviors of high-school students and to determine whether a train-the-trainer model would be feasible in a high-school setting. The research team designed a pilot study. The setting was a Horace Mann charter school within Boston's public school system. Participants were teachers and students at the charter school. The team taught teachers a curriculum that included (1) relaxation strategies, such as breathing and imagery; (2) psychoeducation regarding mind-body pathways; and (3) positive psychology. Teachers implemented this curriculum with students. The research team assessed changes in student outcomes (eg, stress, anxiety, and stress management behaviors) using preintervention/postintervention surveys, including the Perceived Stress Scale (PSS), the State-Trait Anxiety Inventory-Form Y (STAI-Y), the stress management subscale of the Health-promoting Lifestyle Profile II (HPLP-II), the Rosenberg Self-Esteem Scale (RSES), the Locus of Control (LOC) questionnaire, and the Life Orientation Test-Revised (LOTR). Classroom observations using the Classroom Assessment Scoring System (CLASS)-Secondary were also completed to assess changes in classroom environment. Using a Bonferroni correction (P < .007), the study found that students experienced a significant reduction (P < .001) in measures of state-level anxiety on the STAI from pre- to postintervention. The study also found an increase in the use of stress management behaviors at that point. Using a Bonferroni correction (P < .007), the study found that students had significantly less perceived stress (P

  20. Relaxation System

    NASA Technical Reports Server (NTRS)

    1987-01-01

    Environ Corporation's relaxation system is built around a body lounge, a kind of super easy chair that incorporates sensory devices. Computer controlled enclosure provides filtered ionized air to create a feeling of invigoration, enhanced by mood changing aromas. Occupant is also surrounded by multidimensional audio and the lighting is programmed to change colors, patterns, and intensity periodically. These and other sensory stimulators are designed to provide an environment in which the learning process is stimulated, because research has proven that while an individual is in a deep state of relaxation, the mind is more receptive to new information.

  1. Acupuncture and the relaxation response for treating gastrointestinal symptoms in HIV patients on highly active antiretroviral therapy.

    PubMed

    Chang, Bei-Hung; Sommers, Elizabeth

    2011-09-01

    To examine the effect of acupuncture and the relaxation response (RR) for treating gastrointestinal (GI) symptoms in HIV patients who are using highly active antiretroviral therapy (HAART). The authors conducted a 4-arm 2×2 double-blind randomised controlled trial in an acupuncture clinic in the USA. Sham acupuncture and health education were used as the control conditions of real acupuncture and RR elicitation, respectively. Enrolled patients were randomised to real acupuncture+RR (AR), sham acupuncture+RR (SR), real acupuncture+health education (AE) or sham acupuncture+health education (SE) study arm. Participants listened to CDs with RR-eliciting instructions or health education while receiving acupuncture intervention. Interventions were provided twice weekly for 4 weeks and once weekly for another 4 weeks. Participants used daily diaries to record GI symptom severity ratings (0-10). The authors estimated the intervention effect as the changes in symptom rating per intervention session increase using a mixed-effects regression model. A total of 130 people with HIV/AIDS who were on HAART and had persistent GI symptoms were enrolled and 115 started the study intervention. The AR group had greater intervention effects for loose stools symptoms than the other three groups (β=-0.149, -0.151 and -0.144, p value=0.013, 0.013 and 0.018 comparing AR to AE, SR and SE, respectively). The AR group also had significant intervention effects on reducing nausea symptoms when the intervention was given twice per week (β=-0.218, p=0.001). Our trial provided preliminary data demonstrating the potential synergistic effects of acupuncture and RR for treating GI symptoms in HIV patients on HAART.

  2. Nuclear translocation of p19INK4d in response to oxidative DNA damage promotes chromatin relaxation.

    PubMed

    Sonzogni, Silvina V; Ogara, María F; Castillo, Daniela S; Sirkin, Pablo F; Radicella, J Pablo; Cánepa, Eduardo T

    2015-01-01

    DNA is continuously exposed to damaging agents that can lead to changes in the genetic information with adverse consequences. Nonetheless, eukaryotic cells have mechanisms such as the DNA damage response (DDR) to prevent genomic instability. The DNA of eukaryotic cells is packaged into nucleosomes, which fold the genome into highly condensed chromatin, but relatively little is known about the role of chromatin accessibility in DNA repair. p19INK4d, a cyclin-dependent kinase inhibitor, plays an important role in cell cycle regulation and cellular DDR. Extensive data indicate that p19INK4d is a critical factor in the maintenance of genomic integrity and cell survival. p19INK4d is upregulated by various genotoxics, improving the repair efficiency for a variety of DNA lesions. The evidence of p19INK4d translocation into the nucleus and its low sequence specificity in its interaction with DNA prompted us to hypothesize that p19INK4d plays a role at an early stage of cellular DDR. In the present study, we demonstrate that upon oxidative DNA damage, p19INK4d strongly binds to and relaxes chromatin. Furthermore, in vitro accessibility assays show that DNA is more accessible to a restriction enzyme when a chromatinized plasmid is incubated in the presence of a protein extract with high levels of p19INK4d. Nuclear protein extracts from cells overexpressing p19INK4d are better able to repair a chromatinized and damaged plasmid. These observations support the notion that p19INK4d would act as a chromatin accessibility factor that allows the access of the repair machinery to the DNA damage site.

  3. Acupuncture and the relaxation response for treating gastrointestinal symptoms in HIV patients on highly active antiretroviral therapy

    PubMed Central

    Chang, Bei-Hung; Sommers, Elizabeth

    2011-01-01

    Objectives To examine the effect of acupuncture and the relaxation response (RR) for treating gastrointestinal (GI) symptoms in HIV patients who are using highly active antiretroviral therapy (HAART). Methods The authors conducted a 4-arm 2×2 double-blind randomised controlled trial in an acupuncture clinic in the USA. Sham acupuncture and health education were used as the control conditions of real acupuncture and RR elicitation, respectively. Enrolled patients were randomised to real acupuncture+RR (AR), sham acupuncture+RR (SR), real acupuncture+health education (AE) or sham acupuncture+health education (SE) study arm. Participants listened to CDs with RR-eliciting instructions or health education while receiving acupuncture intervention. Interventions were provided twice weekly for 4 weeks and once weekly for another 4 weeks. Participants used daily diaries to record GI symptom severity ratings (0–10). The authors estimated the intervention effect as the changes in symptom rating per intervention session increase using a mixed-effects regression model. Results A total of 130 people with HIV/AIDS who were on HAART and had persistent GI symptoms were enrolled and 115 started the study intervention. The AR group had greater intervention effects for loose stools symptoms than the other three groups (β=−0.149, −0.151 and −0.144, p value=0.013, 0.013 and 0.018 comparing AR to AE, SR and SE, respectively). The AR group also had significant intervention effects on reducing nausea symptoms when the intervention was given twice per week (β=−0.218, p=0.001). Conclusions Our trial provided preliminary data demonstrating the potential synergistic effects of acupuncture and RR for treating GI symptoms in HIV patients on HAART. PMID:21705396

  4. Reduced nitric oxide-mediated relaxation and endothelial nitric oxide synthase expression in the tail arteries of streptozotocin-induced diabetic rats.

    PubMed

    Mokhtar, Siti Safiah; Vanhoutte, Paul M; Leung, Susan Wai Sum; Suppian, Rapeah; Yusof, Mohd Imran; Rasool, Aida Hanum Ghulam

    2016-02-15

    Diabetes is associated with endothelial dysfunction, which is characterized by impaired endothelium-dependent relaxations. The present study aimed to examine the role of nitric oxide (NO), prostacyclin and endothelium-dependent hyperpolarization (EDH), in the relaxation of ventral tail arteries of rats under diabetic conditions. Relaxations of tail arteries of control and diabetic rats were studied in wire myograph. Western blotting and immunostaining were used to determine the presence of proteins. Acetylcholine-induced relaxations were significantly smaller in arteries of diabetic compared to control rats (Rmax; 70.81 ± 2.48% versus 85.05 ± 3.15%). Incubation with the combination of non-selective cyclooxygenase (COX) inhibitor, indomethacin and potassium channel blockers, TRAM 34 and UCL 1684, demonstrated that NO-mediated relaxation was attenuated significantly in diabetic compared to control rats (Rmax; 48.47 ± 5.84% versus 68.39 ± 6.34%). EDH-type (in the presence of indomethacin and NO synthase inhibitor, LNAME) and prostacyclin-mediated (in the presence of LNAME plus TRAM 34 and UCL 1684) relaxations were not significantly reduced in arteries of diabetic compared to control rats [Rmax: (EDH; 17.81 ± 6.74% versus 34.16 ± 4.59%) (prostacyclin; 15.85 ± 3.27% versus 17.23 ± 3.75%)]. Endothelium-independent relaxations to sodium nitroprusside, salbutamol and prostacyclin were comparable in the two types of preparations. Western blotting and immunostaining indicated that diabetes diminished the expression of endothelial NO synthase (eNOS), while increasing those of COX-1 and COX-2. Thus, since acetylcholine-induced NO-mediated relaxation was impaired in diabetes because of reduced eNOS protein expression, pharmacological intervention improving NO bioavailability could be useful in the management of diabetic endothelial dysfunction.

  5. Relaxation Techniques.

    DTIC Science & Technology

    1985-04-01

    FUNDING/SPONSORING 18b. OFFICE SYMBOL 9. PROCUREMENT INSTRUMENT IDENTIFICATION NUMBER ORGANIZATION (If applicable) 8c ADDRESS f( t’, State and ZIP Code) 10...inhaling and exhaling to promote a feeling of relaxation that is used in yoga, LaMaze childbirth, and hypnosis . The sccond is progressive muscle

  6. Gender differences in adolescents' responses to themes of relaxation in cigarette advertising: Relationship to intentions to smoke.

    PubMed

    Dirocco, Danae N; Shadel, William G

    2007-02-01

    Studies have shown that increased exposure to cigarette advertising increases adolescents' risk of smoking and moreover, that gender may play an important role in moderating how cigarette advertisements are viewed and processed. However, information about the particular features of cigarette advertising that interact with gender to promote smoking among adolescents is scarce. The purpose of this study was to examine if gender moderates the degree to which the relaxation valence (i.e., degree to which relaxing themes are emphasized) of cigarette advertisements is related to smoking intentions in a sample of never smoking adolescents. Regardless of brand type (of the seven brands studied), cigarette advertisements that displayed highly relaxing images were associated with increased intentions to smoke among female adolescents only. These results have implications for understanding what features of cigarette advertisements have the most influence among different groups of adolescents.

  7. Cinnamaldehyde and cinnamaldehyde-containing micelles induce relaxation of isolated porcine coronary arteries: role of nitric oxide and calcium

    PubMed Central

    Raffai, Gábor; Kim, Byungkuk; Park, Sanga; Khang, Gilson; Lee, Dongwon; Vanhoutte, Paul M

    2014-01-01

    Background and purpose Cinnamaldehyde, a major component of cinnamon, induces the generation of reactive oxygen species and exerts vasodilator and anticancer effects, but its short half-life limits its clinical use. The present experiments were designed to compare the acute relaxing properties of cinnamaldehyde with those of self-assembling polymer micelles either loaded with cinnamaldehyde or consisting of a polymeric prodrug [poly(cinnamaldehyde)] that incorporates the compound in its backbone. Methods Rings of porcine coronary arteries were contracted with the thromboxane A2 receptor agonist U46619 or 40 mM KCl, and changes in isometric tension were recorded. Results Cinnamaldehyde induced concentration-dependent but endothelium-independent, nitric oxide synthase (NOS)-independent, cyclooxygenase-independent, soluble guanylyl cyclase (sGC)-independent, calcium-activated potassium-independent, and TRPA1 channel-independent relaxations. Cinnamaldehyde also inhibited the contractions induced by 40 mM KCl Ca2+ reintroduction in 40 mM KCl Ca2+-free solution or by the Ca2+ channel opener Bay K8644. Cinnamaldehyde-loaded control micelles induced complete, partly endothelium-dependent relaxations sensitive to catalase and inhibitors of NOS or sGC, but not cyclooxygenase or TRPA1, channels. Cinnamaldehyde-loaded micelles also inhibited contractions induced by 40 mM KCl Ca2+ reintroduction or Bay K8644. Poly(cinnamaldehyde) micelles induced only partial, endothelium-dependent relaxations that were reduced by inhibitors of NOS or sGC and by catalase and the antioxidant tiron, but not by indomethacin or TRPA1 channel blockers. Conclusion The present findings demonstrate that cinnamaldehyde-loaded and poly(cinnamaldehyde) micelles possess vasodilator properties, but that the mechanism underlying the relaxation that they cause differs from that of cinnamaldehyde, and thus could be used both to relieve coronary vasospasm and for therapeutic drug delivery. PMID:24904214

  8. A High Frequency Response Relaxed Eddy Accumulation Flux Measurement System for Sampling Short-Lived Biogenic Volatile Organic Compounds

    EPA Science Inventory

    A second-generation relaxed eddy accumulation system was built and tested with the capability to measure vertical biogenic volatile organic compound (VOC) fluxes at levels as low as 10 µg C m−2 hr−1. The system features a continuous, integrated gas-phase ozo...

  9. A High Frequency Response Relaxed Eddy Accumulation Flux Measurement System for Sampling Short-Lived Biogenic Volatile Organic Compounds

    EPA Science Inventory

    A second-generation relaxed eddy accumulation system was built and tested with the capability to measure vertical biogenic volatile organic compound (VOC) fluxes at levels as low as 10 µg C m−2 hr−1. The system features a continuous, integrated gas-phase ozo...

  10. The Use of Silica Coated MnO Nanoparticles to Control MRI Relaxivity in Response to Specific Physiological Changes

    PubMed Central

    Lee, Yi-Cheng; Chen, Der-Yow; Dodd, Stephen J.; Bouraoud, Nadia; Koretsky, Alan P.; Krishnan, Kannan M.

    2012-01-01

    MnO nanoparticles have been tested to engineer a delayed increase in MRI T1 relaxivity caused by cellular uptake via endocytosis into acidic compartments. Various coatings on core-shell structured MnO nanoparticles were tested for those that had the lowest T1 relaxivity at pH 7.4, a pH where MnO does not dissolve into Mn2+ ions. The rate of dissolution and release of Mn2+ of the different coated MnO particles as well as changes in T1 relaxivity were measured at pH 5, a pH routinely obtained in the endosomal-lysosomal pathway. Of a number of coatings, silica coated MnO (MnO@SiO2) had the lowest relaxivity at pH 7.4 (0.29 mM−1sec−1). About one third of the MnO dissolved within 20 min and the T1 relaxivity increased to that of free Mn2+ (6.10 mM−1sec−1) after three days at pH 5. MRI of MnO@SiO2 particles injected into the rat brain showed time-dependent signal changes consistent with the in vitro rates. Thalamocortical tract-tracing could be observed due to the released Mn2+. Intravenous infusion of MnO@SiO2 particles showed little enhancement in any tissue except gallbladder. The gallbladder enhancement was interpreted to be due to endocytosis by liver cells and excretion of Mn2+ ions into the gallbladder. The MnO@SiO2 core-shell nanoparticles show the best potential for delaying the release of MRI contrast until endocytosis into low pH compartments activate MRI contrast. The delayed enhancement may have benefits for targeting MRI contrast to specific cells and surface receptors that are known to be recycled by endocytosis. PMID:22341582

  11. Electrooptical and Response/Relaxation Properties of Liquid Crystal Cells in In-plane Switching Mode with Polyvinylcinnamate Photoinduced Alignment Layer

    NASA Astrophysics Data System (ADS)

    Zhou, Ying; Sato, Susumu

    1998-08-01

    Using polyvinylcinnamate (PVCi) photoinduced alignment layers and rubbed polyvinylalcohol (PVA) alignment layers, we produced PVCi-PVA and PVA-PVA in-plane switching (IPS) cells. Transmission properties of the two kinds of IPS-mode cells show that it is possible to decrease the driving voltage for the IPS-mode cell with a weak anchoring alignment surface. The response times of the PVCi-PVA cells are almost the same as those of the PVA-PVA cells, however, the measurement results of the relaxation times for the PVCi-PVA cells indicate that they depend on the time of the voltage applied, and the relaxation times increase with the increase of the applying time. Furthermore, we investigate the decline effect of the twist angle of a PVCi-PVA cell with time after a voltage has been applied for a very long time and then removed.

  12. Comparison of relaxation responses of cavernous and trigonal smooth muscles from rabbits by alpha1-adrenoceptor antagonists; prazosin, terazosin, doxazosin, and tamsulosin.

    PubMed Central

    Seo, K. K.; Lee, M. Y.; Lim, S. W.; Kim, S. C.

    1999-01-01

    Alpha1a-adrenergic receptor (AR) primarily mediates the contraction of the prostatic and cavernous smooth muscles. Among clinically available alpha1-AR antagonists for the medical management of benign prostatic hyperplasia (BPH), tamsulosin has a modest selectivity for alpha1A- and alpha1D- over alpha1B-ARs. To compare the effects of various alpha1-AR antagonists on relaxation responses of cavernous and trigonal smooth muscles, isometric tension studies with relatively selective (tamsulosin) and non-selective (prazosin, doxazosin, and terazosin) alpha1A-AR antagonists, were conducted in the cavernous and trigonal muscle strips of rabbits (n=10 each). Tamsulosin had the strongest inhibitory effect on contraction of trigonal smooth muscle among the various alpha1-AR antagonists, and the inhibitory activities of prazosin, doxazosin, and terazosin were not statistically different. All alpha1-AR antagonists caused concentration-dependent relaxation of the cavernous muscle strips. Tamsulosin was shown to have greater potency than prazosin (more than 100-fold), doxazosin (more than 1000-fold), and terazosin (more than 1000-fold), in relaxation of cavernous smooth muscle. In conclusion, tamsulosin might be the most effective drug among the four commonly used alpha1-AR antagonists for the medical management of BPH. Tamsulosin might be a potential substitute for phentolamine in combination with vasoactive agents as an intracavernous injection therapy for patients with erectile dysfunction. PMID:10102527

  13. COX-2-Derived Prostanoids and Oxidative Stress Additionally Reduce Endothelium-Mediated Relaxation in Old Type 2 Diabetic Rats

    PubMed Central

    Vessières, Emilie; Guihot, Anne-Laure; Toutain, Bertrand; Maquigneau, Maud; Fassot, Céline; Loufrani, Laurent; Henrion, Daniel

    2013-01-01

    Endothelial dysfunction in resistance arteries alters end organ perfusion in type 2 diabetes. Superoxides and cyclooxygenase-2 (COX-2) derivatives have been shown separately to alter endothelium-mediated relaxation in aging and diabetes but their role in the alteration of vascular tone in old diabetic subjects is not clear, especially in resistance arteries. Consequently, we investigated the role of superoxide and COX-2-derivatives on endothelium-dependent relaxation in 3 and 12 month-old Zucker diabetic fatty (ZDF) and lean (LZ) rats. Mesenteric resistance arteries were isolated and vascular tone was investigated using wire-myography. Endothelium (acetylcholine)-dependent relaxation was lower in ZDF than in LZ rats (60 versus 84% maximal relaxation in young rats and 41 versus 69% in old rats). Blocking NO production with L-NAME was less efficient in old than in young rats. L-NAME had no effect in old ZDF rats although eNOS expression level in old ZDF rats was similar to that in old LZ rats. Superoxide level and NADPH-oxidase subunits (p67phox and gp91phox) expression level were greater in ZDF than in LZ rats and were further increased by aging in ZDF rats. In young ZDF rats reducing superoxide level with tempol restored acetylcholine-dependent relaxation to the level of LZ rats. In old ZDF rats tempol improved acetylcholine-dependent relaxation without increasing it to the level of LZ rats. COX-2 (immunolabelling and Western-blot) was present in arteries of ZDF rats and absent in LZ rats. In old ZDF rats arterial COX-2 level was higher than in young ZDF rats. COX-2 blockade with NS398 restored in part acetylcholine-dependent relaxation in arteries of old ZDF rats and the combination of tempol and NS398 fully restored relaxation in control (LZ rats) level. Accordingly, superoxide production and COX-2 derivatives together reduced endothelium-dependent relaxation in old ZDF rats whereas superoxides alone attenuated relaxation in young ZDF or old LZ rats. PMID

  14. Active myocyte shortening during the 'isovolumetric relaxation' phase of diastole is responsible for ventricular suction; 'systolic ventricular filling'.

    PubMed

    Buckberg, Gerald D; Castellá, Manuel; Gharib, Morteza; Saleh, Saleh

    2006-04-01

    To study the 'isovolumetric relaxation' phase of rapid ventricular filling by analysis of the shortening of cardiac muscle in the endocardial and epicardial segments of the left ventricle in the dual helical model of the ventricular band, described by Torrent-Guasp. In 10 pigs (27-82 kg), temporal shortening by sonomicrometer crystals was recorded while recording ECG, and measuring intraventricular pressure and dP/dt with Millar pressure transducers. The following sequence was observed; shortening began in descending or endocardial segment, and 82+/-23 ms later it was initiated in the epicardial or ascending segment of the band. The descending segment stops shortening during the rapid filling phase of fast descent of ventricular pressure, but the ascending segment shortening continues for 92+/-33 ms, so that active shortening continues during the period of isovolumetric relaxation. During the rapid filling phase, dopamine decreased the interval between completion of endocardial and termination of epicardial contraction from 92+/-20 to 33+/-8 ms. Conversely propranolol delayed the start of epicardial shortening from 82+/-23 to 121+/-20 ms, and prolonged the duration of endocardial contraction, causing a closer (21+/-5 ms vs 92+/-20 ms) interval between termination of contraction of endocardial and epicardial fibers. The resultant slope of the rapid descent of the left ventricular pressure curve became prolonged. These time sequences show that ongoing unopposed ascending segment shortening occurs during the phase of rapid fall of ventricular pressure. These active shortening phases respond to positive and negative inotropic stimulation, and indicate the classic concept of 'isovolumetric relaxation', IVR, must be reconsidered, and the new term 'isovolumetric contraction', IVC, or systolic ventricular filing may be used.

  15. Natural relaxation

    NASA Astrophysics Data System (ADS)

    Marzola, Luca; Raidal, Martti

    2016-11-01

    Motivated by natural inflation, we propose a relaxation mechanism consistent with inflationary cosmology that explains the hierarchy between the electroweak scale and Planck scale. This scenario is based on a selection mechanism that identifies the low-scale dynamics as the one that is screened from UV physics. The scenario also predicts the near-criticality and metastability of the Standard Model (SM) vacuum state, explaining the Higgs boson mass observed at the Large Hadron Collider (LHC). Once Majorana right-handed neutrinos are introduced to provide a viable reheating channel, our framework yields a corresponding mass scale that allows for the seesaw mechanism as well as for standard thermal leptogenesis. We argue that considering singlet scalar dark matter extensions of the proposed scenario could solve the vacuum stability problem and discuss how the cosmological constant problem is possibly addressed.

  16. Multi-region relaxed magnetohydrodynamics in plasmas with slowly changing boundaries—Resonant response of a plasma slab

    DOE PAGES

    Dewar, R. L.; Hudson, S. R.; Bhattacharjee, A.; ...

    2017-04-03

    The adiabatic limit of a recently proposed dynamical extension of Taylor relaxation, multi-region relaxed magnetohydrodynamics (MRxMHD), is summarized, with special attention to the appropriate definition of a relative magnetic helicity. The formalism is illustrated using a simple two-region, sheared-magnetic-field model similar to the Hahm-Kulsrud-Taylor (HKT) rippled-boundary slab model. In MRxMHD, a linear Grad-Shafranov equation applies, even at finite ripple amplitude. The adiabatic switching on of boundary ripple excites a shielding current sheet opposing reconnection at a resonant surface. The perturbed magnetic field as a function of ripple amplitude is calculated by invoking the conservation of magnetic helicity in the twomore » regions separated by the current sheet. Here, at low ripple amplitude, "half islands" appear on each side of the current sheet, locking the rotational transform at the resonant value. Beyond a critical amplitude, these islands disappear and the rotational transform develops a discontinuity across the current sheet. Published by AIP Publishing.« less

  17. Multi-region relaxed magnetohydrodynamics in plasmas with slowly changing boundaries—Resonant response of a plasma slab

    NASA Astrophysics Data System (ADS)

    Dewar, R. L.; Hudson, S. R.; Bhattacharjee, A.; Yoshida, Z.

    2017-04-01

    The adiabatic limit of a recently proposed dynamical extension of Taylor relaxation, multi-region relaxed magnetohydrodynamics (MRxMHD), is summarized, with special attention to the appropriate definition of a relative magnetic helicity. The formalism is illustrated using a simple two-region, sheared-magnetic-field model similar to the Hahm-Kulsrud-Taylor (HKT) rippled-boundary slab model. In MRxMHD, a linear Grad-Shafranov equation applies, even at finite ripple amplitude. The adiabatic switching on of boundary ripple excites a shielding current sheet opposing reconnection at a resonant surface. The perturbed magnetic field as a function of ripple amplitude is calculated by invoking the conservation of magnetic helicity in the two regions separated by the current sheet. At low ripple amplitude, "half islands" appear on each side of the current sheet, locking the rotational transform at the resonant value. Beyond a critical amplitude, these islands disappear and the rotational transform develops a discontinuity across the current sheet.

  18. Corticotropin releasing factor in urine--a possible biochemical marker of fibromyalgia. Responses to massage and guided relaxation.

    PubMed

    Lund, Irene; Lundeberg, Thomas; Carleson, Joakim; Sönnerfors, Helene; Uhrlin, Björn; Svensson, Elisabeth

    2006-07-31

    The purpose of this preliminary study was to evaluate the relationship between a possible biochemical marker of stress, 24-h urinary concentrations of Corticotropin Releasing Factor-Like Immunoreactivity (CRF-LI), and ratings of stress-related symptoms like depression and anxiety, as well as to evaluate pain and emotional reactions in patients with fibromyalgia (FM). Another purpose was to study the effects of massage and guided relaxation, with respect to change in the same variables. Urine sampling and ratings were performed before treatments, after and 1 month after completed treatments. Concentrations of CRF-LI was analysed with radioimmnoassay technique. For the assessment of depression, anxiety and pain the CPRS-A questionnaire was used and for rated pain and emotional reactions the NHP questionnaire was used. The 24-h urinary concentration of the CRF-LI was found to be related to depression, mood and inability to take initiative. After treatment the urinary CRF-LI concentrations and the rated levels of pain and emotional reactions were found to have decreased. In conclusion, the 24-h urinary CRF-LI concentration may be used as a biochemical marker of stress-related symptoms such as depression in patients with FM and possibly also other conditions characterized by chronic pain. Therapies such as massage and guided relaxation may be tried for the amelioration of pain and stress but further studies are required.

  19. Simvastatin treatment restores vasoconstriction and the inhibitory effect of LPC on endothelial relaxation via affecting oxidizing metabolism in diabetic rats.

    PubMed

    Ceylan, A; Karasu, C; Aktan, F; Ozansoy, G

    2004-08-01

    Oxidative stress and dyslipidaemia play an important role in the development of diabetes-induced vascular complications. The aim of this study was to examine the reversal effects of simvastatin on some metabolic and oxidative parameters, and vascular functions in diabetic rats. Diabetes was induced by a single injection of streptozotocin (STZ, 45 mg/kg, i.p.). Eight weeks after STZ induction, some of the diabetic and control rats were treated with simvastatin (10 mg/kg rat/d) for 4 weeks. Plasma glucose, triglyceride and total cholesterol concentrations were significantly increased in 12-week diabetic rats. Simvastatin treatment stopped the loss of body weight, completely normalized the increase of plasma lipids and partially reduced the hyperglycaemia in diabetic rats. Increased malondialdehyde levels, catalase and glutathione peroxidase activities were normalised by simvastatin treatment in diabetic aorta. Phenylephrine (PE)-induced contractility in aorta rings was unaffected by diabetes, but was markedly decreased after simvastatin treatment in both control and diabetic rats. Reduction of endothelium-dependent vasorelaxation in diabetes was significantly ameliorated by simvastatin treatment. Incubation of aorta rings with lysophosphatidylcholine, a component of the oxidized LDL, did not significantly affect PE-induced contractions, but reduced endothelium-dependent relaxations more in untreated-diabetic rats than in other experimental groups. The endothelium-independent vasorelaxations were similar in all ring preparations. These results indicate that simvastatin treatment may ameliorate diabetes-induced abnormal vasoconstriction and endothelial dysfunction via affecting general and oxidizing metabolism, nitric oxide disability and intracellular calcium mobilisation.

  20. Non-Debye relaxation in the dielectric response of nematic liquid crystals: Surface and memory effects in the adsorption-desorption process of ionic impurities

    NASA Astrophysics Data System (ADS)

    de Paula, J. L.; Santoro, P. A.; Zola, R. S.; Lenzi, E. K.; Evangelista, L. R.; Ciuchi, F.; Mazzulla, A.; Scaramuzza, N.

    2012-11-01

    We demonstrate theoretically that the presence of ions in insulating materials such as nematic liquid crystals may be responsible for the dielectric spectroscopy behavior observed experimentally. It is shown that, at low frequencies, an essentially non-Debye relaxation process takes place due to surface effects. This is accomplished by investigating the effects of the adsorption-desorption process on the electrical response of an electrolytic cell when the generation and recombination of ions is present. The adsorption-desorption is governed by a non-usual kinetic equation in order to incorporate memory effects related to a non-Debye relaxation and the roughness of the surface. The analysis is carried out by searching for solutions to the drift-diffusion equation that satisfy the Poisson equation relating the effective electric field to the net charge density. We also discuss the effect of the mobility of the ions, i.e., situations with equal and different diffusion coefficients for positive and negative ions, on the impedance and obtain an exact expression for the admittance. The model is compared with experimental results measured for the impedance of a nematic liquid crystal sample and a very good agreement is obtained.

  1. Non-Debye relaxation in the dielectric response of nematic liquid crystals: surface and memory effects in the adsorption-desorption process of ionic impurities.

    PubMed

    de Paula, J L; Santoro, P A; Zola, R S; Lenzi, E K; Evangelista, L R; Ciuchi, F; Mazzulla, A; Scaramuzza, N

    2012-11-01

    We demonstrate theoretically that the presence of ions in insulating materials such as nematic liquid crystals may be responsible for the dielectric spectroscopy behavior observed experimentally. It is shown that, at low frequencies, an essentially non-Debye relaxation process takes place due to surface effects. This is accomplished by investigating the effects of the adsorption-desorption process on the electrical response of an electrolytic cell when the generation and recombination of ions is present. The adsorption-desorption is governed by a non-usual kinetic equation in order to incorporate memory effects related to a non-Debye relaxation and the roughness of the surface. The analysis is carried out by searching for solutions to the drift-diffusion equation that satisfy the Poisson equation relating the effective electric field to the net charge density. We also discuss the effect of the mobility of the ions, i.e., situations with equal and different diffusion coefficients for positive and negative ions, on the impedance and obtain an exact expression for the admittance. The model is compared with experimental results measured for the impedance of a nematic liquid crystal sample and a very good agreement is obtained.

  2. Guinea-pig interpubic joint (symphysis pubica) relaxation at parturition: Underlying cellular processes that resemble an inflammatory response

    PubMed Central

    Rodríguez, Horacio A; Ortega, Hugo H; Ramos, Jorge G; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2003-01-01

    Background At term, cervical ripening in coordination with uterine contractions becomes a prerequisite for a normal vaginal delivery. Currently, cervical ripening is considered to occur independently from uterine contractions. Many evidences suggest that cervical ripening resembles an inflammatory process. Comparatively little attention has been paid to the increased flexibility of the pelvic symphysis that occurs in many species to enable safe delivery. The aim of this study was to investigate whether the guinea-pig interpubic joint relaxation process observed during late pregnancy and parturition resembles an inflammatory process. Methods Samples of pubic symphysis were taken from pregnant guinea-pigs sacrificed along gestation, parturition and postpartum. Serial sections of paraffin-embedded tissues were used to measure the interpubic distance on digitalized images, stained with Giemsa to quantify leukocyte infiltration and to describe the vascular area changes, or studied by the picrosirius-polarization method to evaluate collagen remodeling. P4 and E2 serum levels were measured by a sequential immunometric assay. Results Data showed that the pubic relaxation is associated with an increase in collagen remodeling. In addition, a positive correlation between E2 serum levels and the increase in the interpubic distance was found. On the other hand, a leukocyte infiltration in the interpubic tissue around parturition was described, with the presence of almost all inflammatory cells types. At the same time, histological images show an increase in vascular area (angiogenesis). Eosinophils reached their highest level immediately before parturition; whereas for the neutrophilic and mononuclear infiltration higher values were recorded one day after parturition. Correlation analysis showed that eosinophils and mononuclear cells were positively correlated with E2 levels, but only eosinophilic infiltration was associated with collagen remodeling. Additionally, we observed

  3. A high-frequency response relaxed eddy accumulation flux measurement system for sampling short-lived biogenic volatile organic compounds

    NASA Astrophysics Data System (ADS)

    Arnts, Robert R.; Mowry, Fred L.; Hampton, Gary A.

    2013-05-01

    second-generation relaxed eddy accumulation system was built and tested with the capability to measure vertical biogenic volatile organic compound (VOC) fluxes at levels as low as 10 µg C m-2 hr-1. The system features a continuous, integrated gas-phase ozone removal procedure to allow for the measurement of highly reactive species such as β-caryophyllene and polar terpenoids such as linalool. A two-component internal standard continuously added to the accumulators was used to correct for switching-induced volumetric errors and as a check on VOC losses exceeding accumulator tube adsorption limits. In addition, the internal standards were used to demonstrate that accumulators quickly return to target flow rates at segregation valve switching frequencies up to at least 0.8 Hz. The system was able to measure daytime hourly fluxes of individual biogenic VOC including oxygenated terpenoids, monoterpenes, and sesquiterpenes.

  4. Impaired vasodilator response to organic nitrates in isolated basilar arteries

    PubMed Central

    Martens, Dorothee; Kojda, Georg

    2001-01-01

    The differential responsiveness of various sections and regions in the vascular system to the vasodilator activity of organic nitrates is important for the beneficial antiischaemic effects of these drugs. In this study we examined the vasodilator activity of organic nitrates in cerebral arteries, where vasodilation causes substantial nitrate induced headache. Isolated porcine basilar and coronary arteries were subjected to increasing concentrations of glyceryl trinitrate (GTN), isosorbide-5-nitrate (ISMN) and pentaerythritol tetranitrate (PETN). S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and endothelium-dependent vasodilation was investigated for comparison purpose. The vasodilator potency (halfmaximal effective concentration in −logM) of GTN (4.33±0.1, n=8), ISMN (1.61±0.07, n=7) and PETN (>10 μM, n=7) in basilar arteries was more than 100 fold lower than that of GTN (6.52±0.06, n=12), ISMN (3.66±0.08, n=10) and PETN (6.3±0.13, n=8) observed in coronary arteries. In striking contrast, the vasodilator potency of SNAP (halfmaximal effective concentration in −logM) was almost similar in basilar (7.76±0.05, n=7) and coronary arteries (7.59±0.05, n=9). Likewise, no difference in endothelium dependent relaxation was observed. Denudation of the endothelium resulted in a small increase of the vasodilator potency (halfmaximal effective concentration in −logM) of GTN (4.84±0.09, n=7, P<0.03) in basilar arteries and similar results were obtained in the presence of the NO-synthase inhibitor Nω-nitro-L-arginine (4.59±0.05, n=9, P<0.03). These results suggest that cerebral conductance blood vessels such as porcine basilar arteries seems to have a reduced expression and/or activity of certain cellular enzymatic electron transport systems such as cytochrome P450 enzymes, which are necessary to bioconvert organic nitrates to NO. PMID:11156558

  5. Glycation does not modify bovine serum albumin (BSA)-induced reduction of rat aortic relaxation: the response to glycated and nonglycated BSA is lost in metabolic syndrome.

    PubMed

    Rubio-Ruiz, Maria Esther; Díaz-Díaz, Eulises; Cárdenas-León, Mario; Argüelles-Medina, Rabindranath; Sánchez-Canales, Patricia; Larrea-Gallo, Fernando; Soria-Castro, Elizabeth; Guarner-Lans, Verónica

    2008-07-01

    The effects of nonglycated bovine serum albumin (BSA) and advanced glycosylation end products of BSA (AGE-BSA) on vascular responses of control and metabolic syndrome (MS) rats characterized by hypertriglyceridemia, hypertension, hyperinsulinemia, and insulin resistance were studied. Albumin and in vitro prepared AGE-BSA have vascular effects; however, recent studies indicate that some effects of in vitro prepared AGEs are due to the conditions in which they were generated. We produced AGEs by incubating glucose with BSA for 60 days under sterile conditions in darkness and at 37 degrees C. To develop MS rats, male Wistar animals were given 30% sucrose in drinking water since weanling. Six month old animals were used. Blood pressure, insulin, triglycerides, and serum albumin were increased in MS rats. Contraction of aortic rings elicited with norepinephrine was stronger. There were no effects of nonglycated BSA or AGE-BSA on contractions in control or MS rats; however, both groups responded to L-NAME, an inhibitor of nitric oxide synthesis. Arterial relaxation induced using acetylcholine was smaller in MS rats. Nonglycated BSA and AGE-BSA significantly diminished relaxation in a 35% in the control group but the decrease was similar when using nonglycated BSA and AGE-BSA. This decrease was not present in the MS rats and was not due to increased RAGEs or altered biochemical characteristics of BSA. In conclusion, both BSA and AGE-BSA inhibit vascular relaxation in control artic rings. In MS rats the effect is lost possibly due to alterations in endothelial cells that are a consequence of the illness.

  6. La relaxation en pedagogie (Relaxation in Teaching).

    ERIC Educational Resources Information Center

    Dufeu, Bernard

    1989-01-01

    A discussion of the use of relaxation techniques in the language classroom outlines the reasons for their use and specifies procedures for relaxation either lying down or seated as a prelude to instruction. (MSE)

  7. Cyclooxygenase 2 contributes to bradykinin-induced microvascular responses in peripheral arterioles after cardiopulmonary bypass.

    PubMed

    Feng, Jun; Anderson, Kelsey; Liu, Yuhong; Singh, Arun K; Ehsan, Afshin; Sellke, Frank W

    2017-10-01

    Diabetic patients are associated with impaired peripheral microvascular function after cardiopulmonary bypass (CPB) and cardiac surgery. We hypothesized that upregulation of the inducible cyclooxygenase 2 (COX-2) contributes to altered microvascular reactivity of peripheral arterioles in diabetic patients undergoing CPB and cardiac surgery. Skeletal muscle samples of nondiabetic (ND) patients and patients with diabetes mellitus (DM; n = 8 per group) undergoing cardiac surgery were harvested before and after CPB. The protein expression/localization of COX-2 was assayed by Western blotting and immunohistochemistry. Peripheral arterioles were dissected from the harvested skeletal muscle tissue samples, the isolated arterioles (80-180 μm) were cannulated and pressurized, and changes in diameter were measured with video microscopy. In-vitro relaxation responses of precontracted arterioles were examined in the presence of the endothelium-dependent vasodilator bradykinin (10(-10) to 10(-6)M) and in the presence or absence of the selective COX-2 inhibitor NS398 (10(-5)M). The post-CPB protein levels of the inducible COX-2 were significantly increased compared with pre-CPB values in both the ND and DM groups (P < 0.05), whereas, this increase was higher in DM than that of ND (P < 0.05). In the DM arterioles, not the ND vessels, bradykinin-induced relaxation response was inhibited in the presence of the specific COX-2 inhibitor NS398 at baseline (P < 0.05). After CPB, bradykinin-induced relaxation response of the ND and DM arterioles was inhibited in the presence of the specific COX-2 inhibitor NS398, but this effect was more pronounced in the diabetic patients (P < 0.05). Diabetes and CPB are associated with upregulation in COX-2 expression/activation in human peripheral microvasculature. This alteration may lead to altered peripheral microvascular reactivity in diabetic patients undergoing cardiac surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Breathing and Relaxation

    MedlinePlus

    ... Home Health Insights Stress & Relaxation Breathing and Relaxation Breathing and Relaxation Make an Appointment Ask a Question ... level is often dependent on his or her breathing pattern. Therefore, people with chronic lung conditions may ...

  9. Vascular responsiveness to dimethylaminoethyl methacrylate and its degradation products.

    PubMed

    Abebe, Worku; Maddux, William F; Schuster, George S; Lewis, Jill B

    2003-07-01

    The increasing use of acrylate-based resins in dentistry has raised questions about the biocompatibility of these substances with oral tissues. The focus of the present investigation was to assess the responsiveness of blood vessels to the resin polymerization accelerating agent dimethylaminoethyl methacrylate (DMAEMA) and its degradation products dimethylethanolamine (DME) and methacrylic acid (MAA), using the rat aortic ring preparation as a tissue model. DMAEMA induced concentration-dependent relaxation of norepinephrine (NE)-contracted aortic rings with and without endothelium. N-nitro-L-arginine methyl ester (L-NAME) selectively inhibited the endothelium-dependent relaxation induced by DMAEMA, suggesting the release of nitric oxide from the endothelium by DMAEMA. Both indomethacin and glybenclamide attenuated the vasorelaxation elicited by DMAEMA in the presence as well as in the absence of endothelium, providing evidence for the role of vasorelaxant prostanoid(s) and K(ATP) channel activation in the responses observed. On the other hand, while MAA was without any apparent effect on the rat aorta, DMAEMA at high and DME at relatively low concentrations caused contraction of the tissues with and without endothelium in the absence of NE. The DME-induced contraction was inhibited by indomethacin, suggesting the involvement of contractile arachidonic acid metabolite(s) in the action of DME. This observation was supported by the findings of increased thromboxane A(2) (TXA(2)) production in aortic rings incubated with DME. Taken together, the data suggest that both DMAEMA and its degradation product, DME, are vasoactive, inducing vasorelaxation and contraction by various mechanisms that may involve the release of nitric oxide from the endothelium, the activation of smooth muscle K(ATP) channels, and the generation of vasorelaxant prostanoid(s) and TXA(2). These effects may play a role in tissue homeostasis and certain adverse conditions associated with the use of

  10. Relaxation Assessment with Varied Structured Milieu (RELAX).

    ERIC Educational Resources Information Center

    Cassel, Russell N.; Cassel, Susie L.

    1983-01-01

    Describes Relaxation Assessment with Varied Structured Milieu (RELAX), a clinical program designed to assess the degree to which an individual is able to demonstrate self-control for overall general relaxation. The program is designed for use with the Cassel Biosensors biofeedback equipment. (JAC)

  11. Relaxation Assessment with Varied Structured Milieu (RELAX).

    ERIC Educational Resources Information Center

    Cassel, Russell N.; Cassel, Susie L.

    1983-01-01

    Describes Relaxation Assessment with Varied Structured Milieu (RELAX), a clinical program designed to assess the degree to which an individual is able to demonstrate self-control for overall general relaxation. The program is designed for use with the Cassel Biosensors biofeedback equipment. (JAC)

  12. The Effects of the Relaxation Response on Nurses' Level of Anxiety, Depression, Well-Being, Work-Related Stress, and Confidence to Teach Patients.

    PubMed

    Calder Calisi, Catherine

    2017-07-01

    The purpose of this pilot study was threefold: to teach nurses the Relaxation Response ( RR), a relaxation technique created by Benson; to measure the effects of the RR on nurses' levels of anxiety, depression, well-being, and work-related stress; and to explore nurses' confidence in teaching their patients the RR. A wait-list, randomized-control quantitative study design was used. Nurses in the intervention group were trained on the benefits and the technique of the RR and were then asked to practice the RR over an 8-week period. No statistical significance was found in nurses' reported level of anxiety, depression, well-being, and work-related stress. However, the nurses reported greater confidence in teaching this technique to patients ( p < .001). As a strategy for self-care in the workplace, nurses were receptive to learning the RR and reported confidence in using this strategy for their patients. Larger studies may reveal more significant reductions in workplace stress and anxiety for nurses.

  13. Upregulation of heme oxygenase-1 potentiates EDH-type relaxations in the mesenteric artery of the spontaneously hypertensive rat.

    PubMed

    Li, Zhuoming; Wang, Yu; Man, Ricky Y K; Vanhoutte, Paul M

    2013-11-15

    Heme oxygenase (HO) converts heme to carbon monoxide, bilirubin, and free iron. The present study investigated whether or not HO-1 induction improves vascular relaxations attributable to endothelium-dependent hyperpolarization (EDH). Thirty-six-week-old spontaneously hypertensive rats were treated with the HO-1 inducer hemin, the HO inhibitor zinc protoporphyrin IX (II) (ZnPP), the antioxidant apocynin, or combinations of these compounds. Isolated mesenteric arteries were prepared for measurement of isometric tension, protein presence, and production of reactive oxygen species (ROS). Hemin potentiated acetylcholine-evoked EDH-type relaxations in the presence of N(ω)-nitro-L-arginine methyl ester (l-NAME) and indomethacin, while the combined treatment with ZnPP plus hemin prevented these improvements. The intermediate conductance Ca(2+)-activated K(+) channel (IKCa) blocker TRAM-34 and the Na(+)-K(+)-ATPase blocker ouabain significantly impaired these hemin-potentiated relaxations. NS309-induced TRAM-34- and ouabain-sensitive relaxations were enhanced by hemin. K(+)-induced ouabain-sensitive relaxations and the expression of Na(+)-K(+)-ATPase were increased by hemin. Thus HO-1 induction improves EDH-type relaxations by augmented activation of IKCa and the downstream Na(+)-K(+)-ATPase. Treatment with apocynin showed a similar effect as hemin in impairing ROS production, enhancing K(+)-induced relaxations, and increasing Na(+)-K(+)-ATPase expression, without affecting the expression of HO-1. The effects of hemin and apocynin were not additive. These observations suggest that the effect of HO-1 induction on EDH-type relaxations is possibly due to its antioxidant properties. In vitro treatment with bilirubin, but not carbon monoxide, enhanced EDH-type relaxations and K(+)-induced ouabain-sensitive relaxations, suggesting that the production of bilirubin may be also involved. The present findings reveal that HO-1 may be a potential vascular-specific therapeutic strategy

  14. A Comparative Evaluation of Three Relaxation Training Procedures.

    ERIC Educational Resources Information Center

    Brandon, Jeffrey E.

    Comparison was made between the effectiveness of three relaxation training procedures: (1) Behavioral Relaxation Training, which consisted of training in relaxing specific parts of the body and controlling breathing; (2) Meditation (based on Benson's procedure for eliciting the relaxation response); and (3) Seashore Sounds "Attention Focusing,"…

  15. Systems Cancer Biology and the Controlling Mechanisms for the J-Shaped Cancer Dose Response: Towards Relaxing the LNT Hypothesis.

    PubMed

    Lou, In Chio; Zhao, Yuchao; Wu, Yingjie; Ricci, Paolo F

    2012-01-01

    The hormesis phenomena or J-shaped dose response have been accepted as a common phenomenon regardless of the involved biological model, endpoint measured and chemical class/physical stressor. This paper first introduced a mathematical dose response model based on systems biology approach. It links molecular-level cell cycle checkpoint control information to clonal growth cancer model to predict the possible shapes of the dose response curves of Ionizing Radiation (IR) induced tumor transformation frequency. J-shaped dose response curves have been captured with consideration of cell cycle checkpoint control mechanisms. The simulation results indicate the shape of the dose response curve relates to the behavior of the saddle-node points of the model in the bifurcation diagram. A simplified version of the model in previous work of the authors was used mathematically to analyze behaviors relating to the saddle-node points for the J-shaped dose response curve. It indicates that low-linear energy transfer (LET) is more likely to have a J-shaped dose response curve. This result emphasizes the significance of systems biology approach, which encourages collaboration of multidiscipline of biologists, toxicologists and mathematicians, to illustrate complex cancer-related events, and confirm the biphasic dose-response at low doses.

  16. An analytical study of turbulence responses, including horizontal-tail loads, of a control-configured vehicle with relaxed static stability

    NASA Technical Reports Server (NTRS)

    Perry, B., III

    1976-01-01

    A static stability augmentation system (SSAS) with angle-of-attack, pitch-rate, and forward-speed feedback is used to stabilize control-configured rigid vehicles with relaxed static stability. Airplane configurations include a baseline configuration and two representative control-configured vehicle configurations. The first statically unstable configuration has baseline geometry and an aft center of gravity; the second statically unstable configuration has reduced tail length and area and a forward neutral point. Stability, flying-qualities, and maneuverability requirements are imposed on the airplane-SSAS systems. Turbulence responses of the rigid airframe and tail loads are examined in terms of configuration changes for a given control law and in terms of control law changes for a given configuration.

  17. Heart rate and heart rate variability in panic, social anxiety, obsessive-compulsive, and generalized anxiety disorders at baseline and in response to relaxation and hyperventilation.

    PubMed

    Pittig, Andre; Arch, Joanna J; Lam, Chi W R; Craske, Michelle G

    2013-01-01

    It remains unclear if diminished high frequency heart rate variability (HF-HRV) can be found across anxiety disorders. HF-HRV and heart rate (HR) were examined in panic (PD), generalized anxiety (GAD), social anxiety (SAD), and obsessive-compulsive disorder (OCD) relative to healthy controls at baseline and during anxiety stressors. All disorders evidenced diminished baseline HF-HRV relative to controls. Baseline HRV differences were maintained throughout relaxation. For hyperventilation, PD and GAD demonstrated greater HR than controls. Psychotropic medication did not account for HF-HRV differences except in OCD. Age and sex evidenced multiple main effects. Findings suggest that low baseline HF-HRV represents a common index for inhibitory deficits across PD, GAD, and SAD, which is consistent with the notion of autonomic inflexibility in anxiety disorders. Elevated HR responses to hyperventilation, however, are specific to PD and GAD.

  18. Role of arachidonic acid lipoxygenase metabolites in acetylcholine-induced relaxations of mouse arteries

    PubMed Central

    Goldman, Daniel H.; Aggarwal, Nitin T.; Chawengsub, Yuttana; Falck, J. R.; Campbell, William B.

    2011-01-01

    immunoblot analysis and RT-PCR of the aorta and mesenteric arteries demonstrated protein and mRNA expression of leukocyte-type 12/15-LO. Thus, in mouse resistance arteries, 12/15-LO AA metabolites mediate endothelium-dependent relaxations to ACh and AA. PMID:21193584

  19. Characterization of relaxant mechanism of H2 S in mouse corpus cavernosum.

    PubMed

    Aydinoglu, Fatma; Ogulener, Nuran

    2016-04-01

    The aim of this study was to investigate the mechanism of H2 S-induced relaxation in mouse corpus cavernosal tissue. l-cysteine (10(-6) × 10(-3) mol/L) and exogenous H2 S (NaHS; 10(-6) to 10(-3) mol/L) induced concentration-dependent relaxation. l-cysteine-induced relaxations was reduced by d,l-propargylglycine, a cystathionine gamma lyase (CSE) inhibitor but not influenced by aminooxyacetic acid, a cystathionine beta synthase (CBS) inhibitor. l-cysteine induced relaxations, but not of those of H2 S diminished in endothelium-denuded tissues. N(ω) -nitro-l-arginine (l-NA; 10(-4) mol/L), a nitric oxide synthase inhibitor, and ODQ (10(-4) mol/L), a guanylyl cyclase inhibitor, increased the H2 S-induced relaxation. Zaprinast (5 × 10(-6) mol/L) and sildenafil (10(-6) mol/L), phosphodiesterase inhibitors, inhibited H2 S-induced relaxation. Adenylyl cyclase inhibitors N-ethylmaleimide (2.5 × 10(-5) mol/L) and SQ22536 (10(-4) mol/L) reduced relaxation to H2 S. Also, H2 S-induced relaxation was reduced by KCl (50 mmol/L), 4-aminopyridine (10(-3) mol/L), a Kv inhibitor, glibenclamide (10(-5) mol/L), a KATP inhibitor or barium chloride (10(-5) mol/L), a KIR inhibitor. However, H2 S-induced relaxation was not influenced by apamin (10(-6) mol/L), a SKC a (2+) inhibitor, charybdotoxin (10(-7) mol/L), an IKC a (2+) and BKC a (2+) inhibitor or combination of apamin and charybdotoxin. Nifedipine (10(-6) mol/L), an L-type calcium channel blocker and atropine (10(-6) mol/L), a muscarinic receptor blocker, inhibited H2 S-induced relaxation. However, H2 S-induced relaxation was not influenced by ouabain (10(-4) mol/L), a Na(+) /K(+) -ATPase inhibitor. This study suggests that H2 S endogenously synthesizes from l-cysteine by CSE endothelium-dependent in mouse corpus cavernosum tissue, and exogenous H2 S may cause endothelium-independent relaxations via activation of K channels (KATP channel, KV channels, KIR channels), L-type voltage-gated Ca(2+) channels, adenylyl cyclase

  20. IR theory of weak H-bonds: Davydov coupling, Fermi resonances and direct relaxations. I. Basis equations within the linear response theory

    NASA Astrophysics Data System (ADS)

    Chamma, D.; Henri-Rousseau, O.

    1999-09-01

    Infrared and Raman spectral densities of cyclic H-bonded dimers, such as encountered in carboxylic acids, are obtained in a full quantum mechanical way by introducing relaxation effects towards the surroundings in the model of Wójcik [Mol. Phys. 36 (1978) 1757] which accounts for the possibility of simultaneous Davydov coupling (between the two hydrogen bonds involved in a cyclic dimer) and Fermi coupling (between each hydrogen bond and one or several bending modes). The relaxations of the fast stretching modes of the H-bonds and of the bending modes are assumed to be of direct type, and are taken into account in the spirit of the Green formalism by insertion of imaginary damping parameters in the effective hamiltonians. Then, the spectral density is obtained within the framework of the linear response theory by Fourier transform of the time-dependent autocorrelation function either of the dipole moment operator, in the infrared case, or of the tensor of the polarizabilities in the Raman case. Extension to non-resonant fast stretching and bending modes, and to several Fermi resonances is also performed according to Henri-Rousseau and Chamma [Chem. Phys. 229 (1998) 37]. In the undamped case, the equivalence of the present work is established with the theory of Maréchal and Witkowski [J. Chem. Phys. 48 (1968) 3697] by neglecting the Fermi resonances. Moreover, one-to-one correspondences are also shown with the work of Henri-Rousseau and Chamma [Chem. Phys. 229 (1998) 37] by ignoring Davydov coupling, and with that of Rösch and Ratner [J. Chem. Phys. 61 (1974) 3344] by neglecting both Davydov and Fermi couplings. Finally, the use of the symmetry properties which appear in cyclic dimers when neglecting the Fermi resonances, initially performed by Maréchal and Witkowski [J. Chem. Phys. 48 (1968) 3697], is discussed, showing the equivalence with the results of the non-symmetrized treatment.

  1. Equivalent cross-relaxation rate imaging and diffusion weighted imaging for early prediction of response to bevacizumab-containing treatment in colorectal liver metastases-preliminary study.

    PubMed

    Matsushima, Shigeru; Sato, Takeshi; Nishiofuku, Hideyuki; Sato, Yozo; Murata, Shinichi; Kinosada, Yasutomi; Era, Seiichi; Inaba, Yoshitaka

    To evaluate and compare the usefulness of equivalent cross-relaxation rate (ECR) imaging (ECRI) and diffusion-weighted imaging (DWI) in the early prediction of the response of bevacizumab-containing treatments of colorectal liver metastases. Seven patients received bevacizumab-containing treatments for colorectal liver metastases. Serial magnetic resonance imaging was performed to evaluate responses before and 2 weeks after starting chemotherapy. In the ECRI, we adopted the off-resonance technique for preferential saturation of immobile protons to evaluate the ECR values. A single saturation transfer pulse frequency was used at a frequency of 3.5 ppm downfield from the water resonance. In the DWI, the apparent diffusion coefficient (ADC) value commonly used with two b-values was acquired by using diffusion weightings of 0 and 800 s/mm(2). The region of interest of the metastatic lesions in the liver was separately measured by ECRI and DWI. Tumor response was assessed by response evaluation criteria in solid tumors criteria 8 weeks after starting chemotherapy. In this study, we had four responders and three nonresponders. There was a significant difference in the pretreatment ECR values between the responders and nonresponders (P=.01); there was no significant difference in the ADC values between the two groups. Analysis of the percentage difference between the pretreatment and post-treatment values, termed as percentage change, showed that there were no significant differences in the percentage change of the ADC values between both groups; however, the percentage change in the ECR value was significantly greater for the responders than for the nonresponders (-41.6%±17.1% vs. -12.9%±6.9%, respectively; P=.04). The pretreatment ECR value and percentage change of the ECR value 2 weeks after starting chemotherapy were useful parameters in the early prediction of response to bevacizumab-containing treatment in colorectal liver metastases. Copyright © 2016 Elsevier

  2. On the response of nonlinear viscoelastic materials in creep and stress relaxation experiments in the lubricated squeeze flow setting

    NASA Astrophysics Data System (ADS)

    Řehoř, Martin; Pr&oring; ša, Vít; T&oring; ma, Karel

    2016-10-01

    Rigorous analysis of the response of nonlinear materials to step inputs requires one to simultaneously handle the discontinuity, differentiation, and nonlinearity. This task is however beyond the reach of the standard theories such as the classical theory of distributions and presents a considerable mathematical difficulty. New advanced mathematical tools are necessary to handle the challenge. An elegant and relatively easy-to-use framework capable of accomplishing the task is provided by the Colombeau algebra, which is a generalisation of the classical theory of distributions to the nonlinear setting. We use the Colombeau algebra formalism and derive explicit formulae describing the response of incompressible Maxwell viscoelastic fluid subject to step load/deformation in the lubricated squeeze flow setting.

  3. Hypertension increases contractile responses to hydrogen peroxide in resistance arteries through increased thromboxane A2, Ca2+, and superoxide anion levels.

    PubMed

    García-Redondo, Ana Belén; Briones, Ana María; Beltrán, Amada Elia; Alonso, María Jesús; Simonsen, Ulf; Salaices, Mercedes

    2009-01-01

    This study investigated the mechanisms underlying the response to hydrogen peroxide (H(2)O(2)) in mesenteric resistance arteries from spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto (WKY) rats. Arteries were mounted in microvascular myographs for isometric tension recording and for simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)), superoxide anion (O(2)(.)) production was evaluated by dihydroethidium fluorescence and confocal microscopy, and thromboxane A(2) (TXA(2)) production was evaluated by enzyme immunoassay. H(2)O(2) (1-100 microM) induced biphasic responses characterized by a transient endothelium-dependent contraction followed by relaxation. Simultaneous measurements of tension and Ca(2+) showed a greater effect of H(2)O(2) in arteries from hypertensive than normotensive rats. The cyclooxygenase (cox) inhibitor, indomethacin [1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1-H-indole-3-acetic acid] (1 microM); the COX-1 inhibitor, SC-58560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole] (1 microM); the thromboxane (TXA(2)) synthase inhibitor, furegrelate [5-(3-pyridinylmethyl)-2-benzofurancarboxylic acid, sodium salt] (10 microM); and the TXA(2)/prostaglandin H(2) receptor antagonist, SQ 29,548 ([1S-[1.alpha.,2.alpha.(Z),3.alpha.,4.alpha.

  4. Impedance response and dielectric relaxation in co-precipitation derived ferrite (Ni,Zn)Fe{sub 2}O{sub 4} ceramics

    SciTech Connect

    Chen, D. G.; Tang, X. G.; Liu, Q. X.; Jiang, Y. P.; Ma, C. B.; Li, R.

    2013-06-07

    Dielectric spectra and magnetization hysteresis loops were used to investigate the grain size effect with temperature on the electrical and magnetic response of co-precipitation derived spinel (Ni{sub 0.5}Zn{sub 0.5})Fe{sub 2}O{sub 4} (NZFO) ceramics. Remarkable dielectric relaxation phenomena of non-Debye type have been observed in each NZFO ceramics as confirmed by two kinds of Cole-Cole plots of the 1100 Degree-Sign C sintered samples, mainly due to the electron-hopping mechanism between n-type and p-type carriers and interfacial ion effect when applied an increase of temperature. The high and low response of grain and grain-boundary regions were determined by modeling the impedance experimental results on two equivalent RC circuits taking into account grain deep trap states. By employing the modified Arrhenius equation, activation energy values of different sintering temperatures were calculated and analyzed in combination with oxygen vacancy. In addition, the magnetization of various sintering temperature samples is dominated by cation distribution and surface effect in different particle ranges.

  5. Retinol-binding protein 7 is an endothelium-specific PPARγ cofactor mediating an antioxidant response through adiponectin

    PubMed Central

    Hu, Chunyan; Keen, Henry L.; Lu, Ko-Ting; Liu, Xuebo; Davis, Deborah R.; Ibeawuchi, Stella-Rita C.; Vogel, Silke; Quelle, Frederick W.; Sigmund, Curt D.

    2017-01-01

    Impaired PPARγ activity in endothelial cells causes oxidative stress and endothelial dysfunction which causes a predisposition to hypertension, but the identity of key PPARγ target genes that protect the endothelium remain unclear. Retinol-binding protein 7 (RBP7) is a PPARγ target gene that is essentially endothelium specific. Whereas RBP7-deficient mice exhibit normal endothelial function at baseline, they exhibit severe endothelial dysfunction in response to cardiovascular stressors, including high-fat diet and subpressor angiotensin II. Endothelial dysfunction was not due to differences in weight gain, impaired glucose homeostasis, or hepatosteatosis, but occurred through an oxidative stress–dependent mechanism which can be rescued by scavengers of superoxide. RNA sequencing revealed that RBP7 was required to mediate induction of a subset of PPARγ target genes by rosiglitazone in the endothelium including adiponectin. Adiponectin was selectively induced in the endothelium of control mice by high-fat diet and rosiglitazone, whereas RBP7 deficiency abolished this induction. Adiponectin inhibition caused endothelial dysfunction in control vessels, whereas adiponectin treatment of RBP7-deficient vessels improved endothelium-dependent relaxation and reduced oxidative stress. We conclude that RBP7 is required to mediate the protective effects of PPARγ in the endothelium through adiponectin, and RBP7 is an endothelium-specific PPARγ target and regulator of PPARγ activity. PMID:28352663

  6. Altered flexion-relaxation responses exist during asymmetric trunk flexion movements among persons with unilateral lower-limb amputation.

    PubMed

    Hendershot, Brad D; Nussbaum, Maury A

    2014-02-01

    Repetitive exposures to altered gait and movement following lower-limb amputation (LLA) have been suggested to contribute to observed alterations in passive tissue properties and neuromuscular control in/surrounding the lumbar spine. These alterations, in turn, may affect the synergy between passive and active tissues during trunk movements. Eight males with unilateral LLA and eight non-amputation controls completed quasi-static trunk flexion-extension movements in seven distinct conditions of rotation in the transverse plane: 0° (sagittally-symmetric), ±15°, ±30°, and ±45° (sagittally-asymmetric). Electromyographic (EMG) activity of the bilateral lumbar erector spinae and lumbar kinematics were simultaneously recorded. Peak lumbar flexion and EMG-off angles were determined, along with the difference ("DIFF") between these two angles and the magnitude of peak normalized EMG activities. Persons with unilateral LLA exhibited altered and asymmetric synergies between active and passive trunk tissues during both sagittally-symmetric and -asymmetric trunk flexion movements. Specifically, decreased and asymmetric passive contributions to trunk movements were compensated with increases in the magnitude and duration of active trunk muscle responses. Such alterations in trunk passive and active neuromuscular responses may result from repetitive exposures to abnormal gait and movement subsequent to LLA, and may increase the risk for LBP in this population. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Evidence that NO/cGMP/PKG signalling cascade mediates endothelium dependent inhibition of IP₃R mediated Ca²⁺ oscillations in myocytes and pericytes of ureteric microvascular network in situ.

    PubMed

    Borysova, Lyudmyla; Burdyga, Theodor

    2015-12-01

    In ureteric microvessels the antagonistic relationship between Ca(2+) signalling in endothelium and Ca(2+) oscillations in myocytes and pericytes of arterioles and venules involves nitric oxide (NO), but the underlying mechanisms are not well understood. In the present study we investigated the effects of carbachol and NO donor SNAP on Ca(2+) signalling and vasomotor responses of arterioles and venules in intact urteric microvascular network in situ using confocal microscopy. Vasomotor responses of arterioles and venules induced by AVP correlated with the occurrence of Ca(2+) oscillations in the myocytes and pericytes and were not abolished by the removal of Ca(2+) from extracellular fluid. Carbachol-induced rise of intracellular Ca(2+) in endothelium was accompanied by the termination of the Ca(2+) oscillations in myocytes and pericytes. This carbachol-induced inhibitory effect on Ca(2+) oscillations in myocytes and pericytes was reversed by ODQ, an inhibitor of soluble guanylyl cyclase (sGC) and by Rp-8-pCPT-cGMPS, an inhibitor of protein kinase G (PKG). Ca(2+) oscillations in myocytes and pericytes were also effectively blocked by NO donor SNAP. An Inhibitory effect of SNAP was markedly enhanced by zaprinast, a selective inhibitor of cGMP-specific phosphodiesterase-5, and reversed by sGC inhibitor, ODQ and PKG inhibitor, Rp-8-pCPT-cGMPS. The cGMP analogue and selective PKG activator 8pCPT-cGMP also induced inhibition of the AVP-induced Ca(2+) oscillations in myocytes and pericytes. SNAP had no effects on Ca(2+) oscillations induced by caffeine in distributing arcade arterioles. Consequently, we conclude that NO- mediated inhibition of Ca(2+) oscillations in myocytes and pericytes predominantly recruits the cGMP/PKG dependent pathway. The inhibitory effect of NO/cGMP/PKG cascade is associated with suppressed Ca(2+) release from the SR of myocytes and pericytes selectively via the inositol triphosphate receptor (IP3R) channels. Copyright © 2015 The Authors

  8. Protective Effect and Mechanism of Total Flavones from Rhododendron simsii Planch on Endothelium-Dependent Dilatation and Hyperpolarization in Cerebral Ischemia-Reperfusion and Correlation to Hydrogen Sulphide Release in Rats

    PubMed Central

    Han, Jun; He, Guo-Wei; Chen, Zhi-Wu

    2014-01-01

    We for the first time investigated the effect and mechanism of the total flavones of Rhododendron simsii Planch (TFR), a widely-used Chinese herb for a thousand years, on vasodilatation and hyperpolarization in middle cerebral artery (MCA) of rats subject to global cerebral ischemia-reperfusion (CIR). TFR (11~2700 mg/L) evoked dose-dependent vasodilation and hyperpolarization in MCA of both sham and CIR that were partially inhibited by 30 μM N-nitro-L-arginine-methyl-ester and 10 μM indomethacin and further attenuated by endogenous H2S synthese-CSE inhibitor PPG (100 μM) or Ca2+-activated potassium channel (Kca) inhibitor TEA (1 mM). In whole-cell patch clamp recording, TFR remarkably enhanced the outward current that was inhibited by TEA. CIR increased CSE mRNA expression and the contents of H2S that were further increased by TFR. We conclude that, in MCA of CIR rats, TFR induces non-NO and non-PGI2-mediated effects of vasodilatation and hyperpolarization involving Kca and increases CSE mRNA expression level in endothelial cells and H2S content in the cerebrum. These findings suggest that the response induced by TFR is potentially related to endothelium-derived hyperpolarizing factor mediated by the endogenous H2S and promote the use of TFR in protection of brain from ischemia-reperfusion injury. PMID:25050128

  9. Psychophysiological Effects of Progressive Relaxation in Anxiety Neurotic Patients and of Progressive Relaxation and Alpha Feedback in Nonpatients.

    ERIC Educational Resources Information Center

    Lehrer, Paul M.

    1978-01-01

    Compared physiological effects of progressive relaxation, alpha feedback, and a no-treatment condition. Nonpatients showed more psychophysiological habituation than patients in response to hearing very loud tones and to reaction time tasks. Patients showed greater physiological response to relaxation than nonpatients. After relaxation, autonomic…

  10. Latent Period of Relaxation.

    PubMed

    Kobayashi, M; Irisawa, H

    1961-10-27

    The latent period of relaxation of molluscan myocardium due to anodal current is much longer than that of contraction. Although the rate and the grade of relaxation are intimately related to both the stimulus condition and the muscle tension, the latent period of relaxation remains constant, except when the temperature of the bathing fluid is changed.

  11. Training-Induced Improvement of Response Selection and Error Detection in Aging Assessed by Task Switching: Effects of Cognitive, Physical, and Relaxation Training

    PubMed Central

    Gajewski, Patrick D.; Falkenstein, Michael

    2012-01-01

    Cognitive control functions decline with increasing age. The present study examines if different types of group-based and trainer-guided training effectively enhance performance of older adults in a task switching task, and how this expected enhancement is reflected in changes of cognitive functions, as measured in electrophysiological brain activity (event-related potentials). One hundred forty-one healthy participants aged 65 years and older were randomly assigned to one of four groups: physical training (combined aerobic and strength training), cognitive training (paper–pencil and computer-aided), relaxation and wellness (social control group), and a control group that did not receive any intervention. Training sessions took place twice a week for 90 min for a period of 4 months. The results showed a greater improvement of performance for attendants of the cognitive training group compared to the other groups. This improvement was evident in a reduction of mixing costs in accuracy and intraindividual variability of speed, indexing improved maintenance of multiple task sets in working memory, and an enhanced coherence of neuronal processing. These findings were supported by event-related brain potentials which showed higher amplitudes in a number of potentials associated with response selection (N2), allocation of cognitive resources (P3b), and error detection (Ne). Taken together, our findings suggest neurocognitive plasticity of aging brains which can be stimulated by broad and multilayered cognitive training and assessed in detail by electrophysiological methods. PMID:22593740

  12. Magnetic resonance diffusion and relaxation characterization of water in the unfrozen vein network in polycrystalline ice and its response to microbial metabolic products.

    PubMed

    Brown, Jennifer R; Brox, Timothy I; Vogt, Sarah J; Seymour, Joseph D; Skidmore, Mark L; Codd, Sarah L

    2012-12-01

    Polycrystalline ice, as found in glaciers and the ice sheets of Antarctica, is a low porosity porous media consisting of a complicated and dynamic pore structure of liquid-filled intercrystalline veins within a solid ice matrix. In this work, Nuclear Magnetic Resonance measurements of relaxation rates and molecular diffusion, useful for probing pore structure and transport dynamics in porous systems, were used to physically characterize the unfrozen vein network structure in ice and its response to the presence of metabolic products produced by V3519-10, a cold tolerant microorganism isolated from the Vostok ice core. Recent research has found microorganisms that can remain viable and even metabolically active within icy environments at sub-zero temperatures. One potential mechanism of survival for V3519-10 is secretion of an extracellular ice binding protein that binds to the prism face of ice crystals and inhibits ice recrystallization, a coarsening process resulting in crystal growth with ice aging. Understanding the impact of ice binding activity on the bulk vein network structure in ice is important to modeling of frozen geophysical systems and in development of ice interacting proteins for biotechnology applications, such as cryopreservation of cell lines, and manufacturing processes in food sciences. Here, we present the first observations of recrystallization inhibition in low porosity ice containing V3519-10 extracellular protein extract as measured with Nuclear Magnetic Resonance and Magnetic Resonance Imaging. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Magnetic resonance diffusion and relaxation characterization of water in the unfrozen vein network in polycrystalline ice and its response to microbial metabolic products

    NASA Astrophysics Data System (ADS)

    Brown, Jennifer R.; Brox, Timothy I.; Vogt, Sarah J.; Seymour, Joseph D.; Skidmore, Mark L.; Codd, Sarah L.

    2012-12-01

    Polycrystalline ice, as found in glaciers and the ice sheets of Antarctica, is a low porosity porous media consisting of a complicated and dynamic pore structure of liquid-filled intercrystalline veins within a solid ice matrix. In this work, Nuclear Magnetic Resonance measurements of relaxation rates and molecular diffusion, useful for probing pore structure and transport dynamics in porous systems, were used to physically characterize the unfrozen vein network structure in ice and its response to the presence of metabolic products produced by V3519-10, a cold tolerant microorganism isolated from the Vostok ice core. Recent research has found microorganisms that can remain viable and even metabolically active within icy environments at sub-zero temperatures. One potential mechanism of survival for V3519-10 is secretion of an extracellular ice binding protein that binds to the prism face of ice crystals and inhibits ice recrystallization, a coarsening process resulting in crystal growth with ice aging. Understanding the impact of ice binding activity on the bulk vein network structure in ice is important to modeling of frozen geophysical systems and in development of ice interacting proteins for biotechnology applications, such as cryopreservation of cell lines, and manufacturing processes in food sciences. Here, we present the first observations of recrystallization inhibition in low porosity ice containing V3519-10 extracellular protein extract as measured with Nuclear Magnetic Resonance and Magnetic Resonance Imaging.

  14. Reduced endothelial NO-cGMP-mediated vascular relaxation and hypertension in IL-6-infused pregnant rats.

    PubMed

    Orshal, Julia M; Khalil, Raouf A

    2004-02-01

    Placental ischemia during pregnancy is associated with increased plasma cytokines such as interleukin-6 (IL-6), which may contribute to increased vascular resistance and hypertension of pregnancy. We tested the hypothesis that an increase in plasma IL-6 during pregnancy is associated with impaired endothelium-dependent relaxation, enhanced vascular contraction, and hypertension. Systolic blood pressure was measured in virgin and pregnant Sprague-Dawley rats non-treated or infused with IL-6 (200 ng/kg per day for 5 days). Isometric contraction was measured in isolated aortic strips, and endothelial nitric oxide (NO) synthase (eNOS) was measured in aortic homogenate using Western blots. Blood pressure was greater in IL-6-infused (146+/-3) than in control pregnant rats (117+/-2 mm Hg). In endothelium-intact vascular strips, phenylephrine (Phe) caused greater increase in active stress in IL-6-infused (maximum: 10.6+/-0.6) than in control pregnant rats (maximum: 4.1+/-0.3x10(4) N/m2). Acetylcholine (ACh)-induced relaxation of Phe contraction and vascular eNOS protein and nitrite/nitrate production were less in IL-6-infused than in control pregnant rats. N(omega)-nitro-L-arginine methyl ester (10(-4) mol/L), inhibitor of NOS, or 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (10(-5) mol/L), inhibitor of cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe-induced stress in control but not IL-6-infused pregnant rats. Endothelium removal enhanced Phe-induced stress in control but not in IL-6-infused pregnant rats. The blood pressure and vascular Phe-induced contraction, ACh relaxation, and eNOS protein were not different between control and IL-6-infused virgin rats. Thus, an endothelium-dependent NO-cGMP-mediated relaxation pathway is inhibited in systemic vessels of pregnant rats infused with IL-6. The results support a role for IL-6 as a possible mediator of the increased vascular resistance during hypertension of pregnancy.

  15. Reduced endothelial NO-cGMP vascular relaxation pathway during TNF-alpha-induced hypertension in pregnant rats.

    PubMed

    Davis, Justin R; Giardina, Jena B; Green, Gachavis M; Alexander, Barbara T; Granger, Joey P; Khalil, Raouf A

    2002-02-01

    Placental ischemia during pregnancy is thought to release cytokines such as tumor necrosis factor-alpha (TNF-alpha), which may contribute to the increased vascular resistance associated with pregnancy-induced hypertension. We have reported that a chronic twofold elevation in plasma TNF-alpha increases blood pressure in pregnant but not in virgin rats; however, the vascular mechanisms are unclear. We tested the hypothesis that increasing plasma TNF-alpha during pregnancy impairs endothelium-dependent vascular relaxation and enhances vascular reactivity. Active stress was measured in aortic strips of virgin and late-pregnant Sprague-Dawley rats untreated or infused with TNF-alpha (200 ng x kg(-1) x day(-1) for 5 days) to increase plasma level twofold. Phenylephrine (Phe) increased active stress to a maximum of 4.2 +/- 0.4 x 10(3) and 9.9 +/- 0.7 x 10(3) N/m2 in control pregnant and TNF-alpha-infused pregnant rats, respectively. Removal of the endothelium enhanced Phe-induced stress in control but not in TNF-alpha-infused pregnant rats. In endothelium-intact strips, ACh caused greater relaxation of Phe contraction in control than in TNF-alpha-infused pregnant rats. Basal and ACh-induced nitrite/nitrate production was less in TNF-alpha-infused than in control pregnant rats. Pretreatment of vascular strips with 100 microM N(G)-nitro-L-arginine methyl ester, to inhibit nitric oxide (NO) synthase, or 1 microM 1H-[1,2,4]oxadiazolo[4,3-]quinoxalin-1-one, to inhibit cGMP production in smooth muscle, inhibited ACh-induced relaxation and enhanced Phe-induced stress in control but not in TNF-alpha-infused pregnant rats. Phe contraction and ACh relaxation were not significantly different between control and TNF-alpha-infused virgin rats. Thus an endothelium-dependent NO-cGMP-mediated vascular relaxation pathway is inhibited in late-pregnant rats infused with TNF-alpha. The results support a role for TNF-alpha as one possible mediator of the increased vascular resistance

  16. Differential effects of sodium tungstate and vanadyl sulfate on vascular responsiveness to vasoactive agents and insulin sensitivity in fructose-fed rats.

    PubMed

    Al-Awwadi, Najim; Bichon-Laurent, Florence; Dimo, Théophile; Michel, Alain; Portet, Karine; Cros, Gérard; Poucheret, Patrick

    2004-10-01

    High fructose feeding induces insulin resistance, impaired glucose tolerance, and hypertension in rats and mimics most of the features of the metabolic syndrome X. The effects of a 6-week treatment with the transition metals administered in drinking water, vanadium (VOSO4.5H2O, 0.75 mg/mL) or tungsten (Na2O4W, 2 g/mL), were investigated on the reactivity to norepinephrine (NEPI) or acetylcholine (ACh) of thoracic aorta rings isolated from fructose (60%) or standard chow fed rats. Maximal effect (Emax) and pD2 (-log EC50) values were determined in each case in the presence or absence of endothelium, while the degree of insulin resistance was determined using the euglycemic hyper insulinemic glucose clamp technique. Aortic segments isolated from 6-week fructose-fed animals were characterized by NEPI hyperresponsiveness (increase in Emax) and endothelium-dependent NEPI supersensitivity (increase in pD2) without any change in the reactivity to ACh. Vanadium or tungsten administered in fructose-fed animals prevented both hypertension and NEPI hyperresponsiveness, while vanadium, but not tungsten, reduced NEPI supersensitivity. Vanadium, but not tungsten, increased the relaxing activity of ACh, both in control and fructose-fed animals. Insulin resistance associated with high fructose feeding was reversed by vanadium but not by tungsten treatment. The differential effects of the two transition metals on vascular responsiveness to NEPI or ACh may be explained by their differential effects on insulin sensitivity.

  17. Contribution of Piezo2 to Endothelium-Dependent Pain.

    PubMed

    Ferrari, Luiz F; Bogen, Oliver; Green, Paul; Levine, Jon D

    2015-01-01

    We evaluated the role of a mechanically-gated ion channel, Piezo2, in mechanical stimulation-induced enhancement of hyperalgesia produced by the pronociceptive vasoactive mediator endothelin-1, an innocuous mechanical stimulus-induced enhancement of hyperalgesia that is vascular endothelial cell dependent. We also evaluated its role in a preclinical model of a vascular endothelial cell dependent painful peripheral neuropathy. The local administration of oligodeoxynucleotides antisense to Piezo2 mRNA, at the site of nociceptive testing in the rat's hind paw, but not intrathecally at the central terminal of the nociceptor, prevented innocuous stimulus-induced enhancement of hyperalgesia produced by endothelin-1 (100 ng). The mechanical hyperalgesia induced by oxaliplatin (2 mg/kg. i.v.), which was inhibited by impairing endothelial cell function, was similarly attenuated by local injection of the Piezo2 antisense. Polymerase chain reaction analysis demonstrated for the first time the presence of Piezo2 mRNA in endothelial cells. These results support the hypothesis that Piezo2 is a mechano-transducer in the endothelial cell where it contributes to stimulus-dependent hyperalgesia, and a model of chemotherapy-induced painful peripheral neuropathy. © 2015 Ferrari et al.

  18. Contribution of Piezo2 to endothelium-dependent pain.

    PubMed

    Ferrari, Luiz F; Bogen, Oliver; Green, Paul; Levine, Jon D

    2015-10-24

    We evaluated the role of a mechanically-gated ion channel, Piezo2, in mechanical stimulation-induced enhancement of hyperalgesia produced by the pronociceptive vasoactive mediator endothelin-1, an innocuous mechanical stimulus-induced enhancement of hyperalgesia that is vascular endothelial cell dependent. We also evaluated its role in a preclinical model of a vascular endothelial cell dependent painful peripheral neuropathy. The local administration of oligodeoxynucleotides antisense to Piezo2 mRNA, at the site of nociceptive testing in the rat's hind paw, but not intrathecally at the central terminal of the nociceptor, prevented innocuous stimulus-induced enhancement of hyperalgesia produced by endothelin-1 (100 ng). The mechanical hyperalgesia induced by oxaliplatin (2 mg/kg. i.v.), which was inhibited by impairing endothelial cell function, was similarly attenuated by local injection of the Piezo2 antisense. Polymerase chain reaction analysis demonstrated for the first time the presence of Piezo2 mRNA in endothelial cells. These results support the hypothesis that Piezo2 is a mechano-transducer in the endothelial cell where it contributes to stimulus-dependent hyperalgesia, and a model of chemotherapy-induced painful peripheral neuropathy.

  19. Relaxation Techniques for Trauma.

    PubMed

    Scotland-Coogan, Diane; Davis, Erin

    2016-01-01

    Physiological symptoms of posttraumatic stress disorder (PTSD) manifest as increased arousal and reactivity seen as anger outburst, irritability, reckless behavior with no concern for consequences, hypervigilance, sleep disturbance, and problems with focus (American Psychiatric Association, 2013 ). In seeking the most beneficial treatment for PTSD, consideration must be given to the anxiety response. Relaxation techniques are shown to help address the physiological manifestations of prolonged stress. The techniques addressed by the authors in this article include mindfulness, deep breathing, yoga, and meditation. By utilizing these techniques traditional therapies can be complemented. In addition, those who are averse to the traditional evidence-based practices or for those who have tried traditional therapies without success; these alternative interventions may assist in lessening physiological manifestations of PTSD. Future research studies assessing the benefits of these treatment modalities are warranted to provide empirical evidence to support the efficacy of these treatments.

  20. Reduced activity of SKCa and Na-K ATPase underlies the accelerated impairment of EDH-type relaxations in mesenteric arteries of aging spontaneously hypertensive rats

    PubMed Central

    Kong, Billy W C; Man, Ricky Y K; Gao, Yuansheng; Vanhoutte, Paul M; Leung, Susan W S

    2015-01-01

    Aging is accompanied by endothelial dysfunction due to reduced bioavailability of nitric oxide (NO) and/or reduced endothelium-dependent hyperpolarizations (EDH). This study examines the hypothesis that hypertension aggravates the impairment of EDH-type relaxation due to aging. EDH-type relaxations were studied in superior mesenteric arteries isolated from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats of 12, 36, 60, and 72 weeks of age. EDH-type relaxations in WKY were reduced with aging, and this was associated with an impairment of the function of small-conductance calcium-activated potassium channels (SKCa) and sodium-potassium ATPase (Na-K ATPase). EDH-type relaxation in SHR was smaller than that in WKY arteries, and further reduction occurred with aging. Pharmacological experiments suggested a reduced involvement of SKCa and Na-K ATPase and activation of adenosine monophosphate-activated protein kinase and silent information regulator T1 (sirtuin-1; SIRT1) in mesenteric arteries of 12-week-old SHR. These pharmacological findings suggest that in superior mesenteric arteries of the rat, the reduction in EDH-type relaxation occurs with aging and that such a reduction is exacerbated in hypertension. The latter exacerbation appears to involve proteins associated with the process of cellular senescence and is related to impaired function of SKCa and Na-K ATPase, a phenomenon that is also observed in mesenteric arteries of older normotensive rats. PMID:26171229

  1. Reduced activity of SKC a and Na-K ATPase underlies the accelerated impairment of EDH-type relaxations in mesenteric arteries of aging spontaneously hypertensive rats.

    PubMed

    Kong, Billy W C; Man, Ricky Y K; Gao, Yuansheng; Vanhoutte, Paul M; Leung, Susan W S

    2015-06-01

    Aging is accompanied by endothelial dysfunction due to reduced bioavailability of nitric oxide (NO) and/or reduced endothelium-dependent hyperpolarizations (EDH). This study examines the hypothesis that hypertension aggravates the impairment of EDH-type relaxation due to aging. EDH-type relaxations were studied in superior mesenteric arteries isolated from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats of 12, 36, 60, and 72 weeks of age. EDH-type relaxations in WKY were reduced with aging, and this was associated with an impairment of the function of small-conductance calcium-activated potassium channels (SKC a) and sodium-potassium ATPase (Na-K ATPase). EDH-type relaxation in SHR was smaller than that in WKY arteries, and further reduction occurred with aging. Pharmacological experiments suggested a reduced involvement of SKC a and Na-K ATPase and activation of adenosine monophosphate-activated protein kinase and silent information regulator T1 (sirtuin-1; SIRT1) in mesenteric arteries of 12-week-old SHR. These pharmacological findings suggest that in superior mesenteric arteries of the rat, the reduction in EDH-type relaxation occurs with aging and that such a reduction is exacerbated in hypertension. The latter exacerbation appears to involve proteins associated with the process of cellular senescence and is related to impaired function of SKC a and Na-K ATPase, a phenomenon that is also observed in mesenteric arteries of older normotensive rats.

  2. Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease

    PubMed Central

    Jacquart, Jolene; Scult, Matthew A.; Slipp, Lauren; Riklin, Eric Isaac Kagan; Lepoutre, Veronique; Comosa, Nicole; Norton, Beth-Ann; Dassatti, Allison; Rosenblum, Jessica; Thurler, Andrea H.; Surjanhata, Brian C.; Hasheminejad, Nicole N.; Kagan, Leslee; Slawsby, Ellen; Rao, Sowmya R.; Macklin, Eric A.; Fricchione, Gregory L.; Benson, Herbert; Libermann, Towia A.; Korzenik, Joshua; Denninger, John W.

    2015-01-01

    Introduction Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) can profoundly affect quality of life and are influenced by stress and resiliency. The impact of mind-body interventions (MBIs) on IBS and IBD patients has not previously been examined. Methods Nineteen IBS and 29 IBD patients were enrolled in a 9-week relaxation response based mind-body group intervention (RR-MBI), focusing on elicitation of the RR and cognitive skill building. Symptom questionnaires and inflammatory markers were assessed pre- and post-intervention, and at short-term follow-up. Peripheral blood transcriptome analysis was performed to identify genomic correlates of the RR-MBI. Results Pain Catastrophizing Scale scores improved significantly post-intervention for IBD and at short-term follow-up for IBS and IBD. Trait Anxiety scores, IBS Quality of Life, IBS Symptom Severity Index, and IBD Questionnaire scores improved significantly post-intervention and at short-term follow-up for IBS and IBD, respectively. RR-MBI altered expression of more genes in IBD (1059 genes) than in IBS (119 genes). In IBD, reduced expression of RR-MBI response genes was most significantly linked to inflammatory response, cell growth, proliferation, and oxidative stress-related pathways. In IBS, cell cycle regulation and DNA damage related gene sets were significantly upregulated after RR-MBI. Interactive network analysis of RR-affected pathways identified TNF, AKT and NF-κB as top focus molecules in IBS, while in IBD kinases (e.g. MAPK, P38 MAPK), inflammation (e.g. VEGF-C, NF-κB) and cell cycle and proliferation (e.g. UBC, APP) related genes emerged as top focus molecules. Conclusions In this uncontrolled pilot study, participation in an RR-MBI was associated with improvements in disease-specific measures, trait anxiety, and pain catastrophizing in IBS and IBD patients. Moreover, observed gene expression changes suggest that NF-κB is a target focus molecule in both IBS and IBD—and that

  3. The relaxation response resiliency program (3RP) in patients with neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis: results from a pilot study.

    PubMed

    Vranceanu, Ana-Maria; Merker, Vanessa L; Plotkin, Scott R; Park, Elyse R

    2014-10-01

    NF1, NF2, and Schwannomatosis are incurable tumor suppressor syndromes associated with poor quality of life. The aim of this study was to determine the feasibility, acceptability, and preliminary efficacy of an NF adapted, 8-week group mind body skills based intervention, the relaxation response resiliency program (3RP) aimed at improving resiliency and increasing satisfaction with life. Patients seen at MGH's Neurofibromatosis Clinic were offered participation if they described difficulties coping to a treating physician. Participants completed measures of life satisfaction, resiliency, stress, mood, lifestyle, pain, post-traumatic growth and mindfulness at baseline and after completing the 3RP program. The intervention had relative feasible enrollment rate (48% rate, 32 out of 67 of patients signing the informed consent form). However, out of the 32 patients who signed the informed consent, only 20 started the study (62.5%) and only 16 completed it (50%), suggesting problems with feasibility. The main reason cited for non-participation was burden of travel to the clinic. The intervention was highly acceptable, as evidenced by an 80% completion rate (16/20). Paired t tests showed significant improvement in resiliency, satisfaction with life, depression, stress, anxiety, mindfulness and post traumatic growth, with effect sizes ranging from 0.73-1.33. There was a trend for significance for improvement in somatization and sleepiness (p = 0.06), with effect sizes of 0.54-0.92 respectively. Statistically nonsignificant improvement was observed in all other measures, with effect sizes small to medium. In sum, the 3RP was found to be relatively feasible, highly acceptable and preliminary efficacious in decreasing symptom burden in this population, supporting the need of a randomized controlled trial.

  4. Multiphasic stress relaxation response of freshly isolated and cultured vascular smooth muscle cells measured by quasi-in situ tensile test.

    PubMed

    Nagayama, Kazuaki; Saito, Shunsuke; Matsumoto, Takeo

    2015-01-01

    Vascular smooth muscle cells (SMCs) undergo a phenotypic change from a contractile to a synthetic state under pathological conditions, such as atherogenesis and restenosis. Although the viscoelastic properties of SMCs are of particular interest because of their role in the development of these vascular diseases, the effects of phenotypic changes on their viscoelastic properties are unclear at this stage. We performed the stress relaxation test at constant strain (ε=30%) for the freshly isolated contractile SMCs (FSMCs) and the cultured synthetic SMCs (CSMCs) maintaining in situ cell shape and cytoskeletal integrity. We also investigated the effect of extracellular Ca2+ on their viscoelastic behaviors. FSMCs and CSMCs exhibited multiphasic stress relaxation, which consisted of rapid relaxation, occurring on a time scale of several seconds and several 10 seconds, and slow relaxation occurring on a time scale of 1000 seconds. The estimated elastic modulus of CSMCs was less than one-half that of FSMCs, that was associated with a decreased of amount of actin stress fibers (SFs) during the transition from contractile to synthetic phenotypes. FSMCs showed a conservation of tension with extracellular Ca2+ following rapid stress relaxation. In contrast, CSMCs showed a consecutive decrease in tension independent of Ca2+. This suggests that the decrease in tension in a long time scale may be involved in mechanical remodeling of SFs induced through a Rho-dependent pathway, which is Ca2+-independent and become predominant in the transition from contractile to synthetic phenotypes.

  5. PARAMAGNETIC RELAXATION IN CRYSTALS.

    DTIC Science & Technology

    CRYSTALS, PARAMAGNETIC RESONANCE, RELAXATION TIME , CRYSTAL DEFECTS, QUARTZ, GLASS, STRAIN(MECHANICS), TEMPERATURE, NUCLEAR SPINS, HYDROGEN, CALCIUM COMPOUNDS, FLUORIDES, COLOR CENTERS, PHONONS, OXYGEN.

  6. Adenoviral expression of 15-lipoxygenase-1 in rabbit aortic endothelium: role in arachidonic acid-induced relaxation.

    PubMed

    Aggarwal, Nitin T; Holmes, Blythe B; Cui, Lijie; Viita, Helena; Yla-Herttuala, Seppo; Campbell, William B

    2007-02-01

    Endothelium-dependent vasorelaxation of the rabbit aorta is mediated by either nitric oxide (NO) or arachidonic acid (AA) metabolites from cyclooxygenase (COX) and 15-lipoxygenase (15-LO) pathways. 15-LO-1 metabolites of AA, 11,12,15-trihydroxyeicosatrienoic acid (THETA), and 15-hydroxy-11,12-epoxyeicosatrienoic acid (HEETA) cause concentration-dependent relaxation. We tested the hypothesis that in the 15-LO pathway of AA metabolism, 15-LO-1 is sufficient and is the rate-limiting step in inducing relaxations in rabbit aorta. Aorta and rabbit aortic endothelial cells were treated with adenoviruses containing human 15-LO-1 cDNA (Ad-15-LO-1) or beta-galactosidase (Ad-beta-Gal). Ad-15-LO-1-transduction increased the expression of a 75-kDa protein corresponding to 15-LO-1, detected by immunoblotting with an anti-human15-LO-1 antibody, and increased the production of HEETA and THETA from [(14)C]AA. Immunohistochemical studies on Ad-15-LO-1-transduced rabbit aorta showed the presence of 15-LO-1 in endothelial cells. Ad-15-LO-1-treated aortic rings showed enhanced relaxation to AA (max 31.7 +/- 3.2%) compared with Ad-beta-Gal-treated (max 12.7 +/- 3.2%) or control nontreated rings (max 13.1 +/- 1.6%) (P < 0.01). The relaxations in Ad-15-LO-1-treated aorta were blocked by the 15-LO inhibitor cinnamyl-3,4-dihydroxy-a-cyanocinnamate. Overexpression of 15-LO-1 in the rabbit aortic endothelium is sufficient to increase the production of the vasodilatory HEETA and THETA and enhance the relaxations to AA. This confirms the role of HEETA and THETA as endothelium-derived relaxing factors.

  7. Music assisted progressive muscle relaxation, progressive muscle relaxation, music listening, and silence: a comparison of relaxation techniques.

    PubMed

    Robb, S L

    2000-01-01

    The purpose of this study was to compare the effects of music assisted progressive muscle relaxation (M + PMR), progressive muscle relaxation (PMR), music listening, and silence/suggestion on measures of anxiety and perceived relaxation. The study also examined participant responses to a posttreatment questionnaire to identify relationships between musical and nonmusical elements in relaxation techniques. Sixty university students participated in the study. Fifteen participants were randomly assigned to each treatment condition. Subjects were tested individually using the same relaxation script for M + PMR and PMR conditions. One-way analyses of covariance were computed to compare pre and posttest differences among groups. Results of the ANCOVA revealed no differences among groups for the State Trait Anxiety Inventory (STAI) or the Visual Analog Scale (VAS). Analysis of variance, however, revealed each treatment condition to be equally effective in producing significant changes in anxiety and perceived relaxation from the pre to posttest period. Additionally, mean score differences revealed decreases for all conditions with M + PMR eliciting the greatest amount of change. A content analysis of posttreatment questionnaire items revealed detailed information about each participant's relaxation experience, state of mind, and use of self-generated relaxation techniques.

  8. Enthalpy relaxation and annealing effect in polystyrene.

    PubMed

    Sakatsuji, Waki; Konishi, Takashi; Miyamoto, Yoshihisa

    2013-07-01

    The effects of thermal history on the enthalpy relaxation in polystyrene are studied by differential scanning calorimetry. The temperature dependence of the specific heat in the liquid and the glassy states, that of relaxation time, and the exponent of the Kohlrausch-Williams-Watts function are determined by measurements of the thermal response against sinusoidal temperature variation. A phenomenological model equation previously proposed to interpret the memory effect in the frozen state is applied to the enthalpy relaxation and the evolution of entropy under a given thermal history is calculated. The annealing below the glass transition temperature produces two effects on enthalpy relaxation: the decay of excess entropy with annealing time in the early stage of annealing and the increase in relaxation time due to physical aging in the later stage. The crossover of these effects is reflected in the variation of temperature of the maximum specific heat observed in the heating process after annealing and cooling.

  9. TEACHING NEUROMUSCULAR RELAXATION.

    ERIC Educational Resources Information Center

    NORRIS, JEANNE E.; STEINHAUS, ARTHUR H.

    THIS STUDY ATTEMPTED TO FIND OUT WHETHER (1) THE METHODS FOR ATTAINING NEUROMUSCULAR RELAXATION THAT HAVE PROVED FRUITFUL IN THE ONE-TO-ONE RELATIONSHIP OF THE CLINIC CAN BE SUCCESSFULLY ADAPTED TO THE TEACHER-CLASS RELATIONSHIP OF THE CLASSROOM AND GYMNASIUM, AND (2) NEUROMUSCULAR RELAXATION CAN BE TAUGHT SUCCESSFULLY BY AN APPROPRIATELY TRAINED…

  10. Relaxation of magnetotail plasmas

    NASA Technical Reports Server (NTRS)

    Bhattacharjee, A.

    1987-01-01

    A quasi-thermodynamic model is presented for the relaxation of magnetotail plasmas during substorms, followed by quiet times. It is proposed that the plasma relaxes to a state of low-potential energy subject to a small number of global constraints. The constraints are exactly preserved by all ideal motions and, approximately, by a wide class of motions of the plasma undergoing magnetic reconnection. A variational principle which minimizes the free energy predicts the relaxed state. Exact, two-dimensional solutions of the relaxed state are obtained. A universal feature of the exact solutions is a chain of magnetic islands along the tail axis. Sufficient conditions for the stability of relaxed states are obtained from the second variation of the free-energy functional.

  11. Effects of sulphite supplementation on vascular responsiveness in sulphite oxidase-deficient rats.

    PubMed

    Nacitarhan, Cahit; Kucukatay, Vural; Sadan, Gulay; Ozturk, Oktay Hasan; Agar, Aysel

    2008-03-01

    1. The aim of the present study was to explore the effect of dietary sulphite supplementation on vascular responsiveness in sulphite oxidase (SO)-deficient rats. 2. Male albino rats were divided into four groups, namely control (n = 8), sulphite-treated (n = 8), SO-deficient (n = 8) and sulphite-treated SO-deficient (n = 8) groups. Sulphite oxidase deficiency was induced by administration of a low-molybdenum diet with concurrent addition of 200 p.p.m. tungsten in the form of sodium tungstate in the drinking water for 9 weeks. Sulphite, in the form of sodium metabisulphite (Na(2)O(5)S(2); 25 mg/kg) was given in the drinking water to sulphite-treated and sulphite-treated SO-deficient groups for the last 6 weeks. The vascular responsiveness of isolated aortic rings to acetylcholine (ACh), sodium nitroprusside (SNP) and histamine was investigated in organ baths. 3. The responsiveness of aortic rings to SNP and histamine did not differ significantly between groups. Conversely, there was a significant decrease in ACh-induced relaxation in aortic rings from the sulphite-treated SO-deficient group compared with the control group (pD(2) 6.2 +/- 0.3 and 7.5 +/- 0.1, respectively; P < 0.05). Incubation of aortic rings in the presence of either l-arginine or superoxide dismutase significantly improved the ACh-induced vasorelaxation in sulphite-treated SO-deficient group (pD(2) 7.2 +/- 0.3 and 7.4 +/- 0.3, respectively). 4. The findings of the present study suggest that the increased production of reactive oxygen species and the resultant increment in l-arginine/nitric oxideconsumption may play a role in the reduced endothelium-dependent vasorelaxation in sulphite-treated SO-deficient rats.

  12. Grape-Derived Polyphenols Prevent Doxorubicin-Induced Blunted EDH-Mediated Relaxations in the Rat Mesenteric Artery: Role of ROS and Angiotensin II.

    PubMed

    Idris-Khodja, Noureddine; Di Marco, Paola; Farhat, Mona; Geny, Bernard; Schini-Kerth, Valérie B

    2013-01-01

    This study determined whether doxorubicin, an anticancer agent, impairs endothelium-dependent relaxations mediated by nitric oxide (NO) and endothelium-derived hyperpolarization (EDH) in the mesenteric artery and, if so, the mechanism underlying the protective effect of red wine polyphenols (RWPs), a rich natural source of antioxidants. Male Wistar rats were assigned into 4 groups: control, RWPs, doxorubicin, and doxorubicin + RWPs. Vascular reactivity was assessed in organ chambers; the vascular formation of reactive oxygen species (ROS) using dihydroethidine and the expression levels of small and intermediate conductance calcium-activated potassium channels (SKCa, IKCa) and connexin 40 (Cx40), which are involved in EDH-type relaxations, endothelial NO synthase (eNOS), angiotensin II, and AT1 receptors by immunofluorescence. The doxorubicin treatment impaired EDH-mediated relaxations, whereas those mediated by NO were minimally affected. This effect was associated with reduced expression levels of SKCa, IKCa, and Cx40, increased expression levels of eNOS, angiotensin II, and AT1 receptors, and formation of ROS in mesenteric arteries. RWPs prevented both the doxorubicin-induced blunted EDH-type relaxations and the increased vascular oxidative stress, and they improved the expression levels of target proteins. These findings suggest that polyphenol-rich natural products might be of interest in the management of doxorubicin-induced vascular injury possibly by improving the vascular angiotensin system.

  13. Grape-Derived Polyphenols Prevent Doxorubicin-Induced Blunted EDH-Mediated Relaxations in the Rat Mesenteric Artery: Role of ROS and Angiotensin II

    PubMed Central

    Idris-Khodja, Noureddine; Di Marco, Paola; Farhat, Mona; Geny, Bernard; Schini-Kerth, Valérie B.

    2013-01-01

    This study determined whether doxorubicin, an anticancer agent, impairs endothelium-dependent relaxations mediated by nitric oxide (NO) and endothelium-derived hyperpolarization (EDH) in the mesenteric artery and, if so, the mechanism underlying the protective effect of red wine polyphenols (RWPs), a rich natural source of antioxidants. Male Wistar rats were assigned into 4 groups: control, RWPs, doxorubicin, and doxorubicin + RWPs. Vascular reactivity was assessed in organ chambers; the vascular formation of reactive oxygen species (ROS) using dihydroethidine and the expression levels of small and intermediate conductance calcium-activated potassium channels (SKCa, IKCa) and connexin 40 (Cx40), which are involved in EDH-type relaxations, endothelial NO synthase (eNOS), angiotensin II, and AT1 receptors by immunofluorescence. The doxorubicin treatment impaired EDH-mediated relaxations, whereas those mediated by NO were minimally affected. This effect was associated with reduced expression levels of SKCa, IKCa, and Cx40, increased expression levels of eNOS, angiotensin II, and AT1 receptors, and formation of ROS in mesenteric arteries. RWPs prevented both the doxorubicin-induced blunted EDH-type relaxations and the increased vascular oxidative stress, and they improved the expression levels of target proteins. These findings suggest that polyphenol-rich natural products might be of interest in the management of doxorubicin-induced vascular injury possibly by improving the vascular angiotensin system. PMID:24066014

  14. The procyanidin-induced pseudo laminar shear stress response: a new concept for the reversal of endothelial dysfunction.

    PubMed

    Corder, Roger; Warburton, Richard C; Khan, Noorafza Q; Brown, Ruth E; Wood, Elizabeth G; Lees, Delphine M

    2004-11-01

    Reduced endothelium-dependent vasodilator responses with increased synthesis of ET-1 (endothelin-1) are characteristics of endothelial dysfunction in heart failure and are predictive of mortality. Identification of treatments that correct these abnormalities may have particular benefit for patients who become refractory to current regimens. Hawthorn preparations have a long history in the treatment of heart failure. Therefore we tested their inhibitory effects on ET-1 synthesis by cultured endothelial cells. These actions were compared with that of GSE (grape seed extract), as the vasoactive components of both these herbal remedies are mainly oligomeric flavan-3-ols called procyanidins. This showed extracts of hawthorn and grape seed were equipotent as inhibitors of ET-1 synthesis. GSE also produced a potent endothelium-dependent vasodilator response on preparations of isolated aorta. Suppression of ET-1 synthesis at the same time as induction of endothelium-dependent vasodilation is a similar response to that triggered by laminar shear stress. Based on these results and previous findings, we hypothesize that through their pharmacological properties procyanidins stimulate a pseudo laminar shear stress response in endothelial cells, which helps restore endothelial function and underlies the benefit from treatment with hawthorn extract in heart failure.

  15. Relaxation Techniques for Health

    MedlinePlus

    ... for posttraumatic stress disorder have had inconsistent results. Rheumatoid Arthritis There’s limited evidence that biofeedback or other relaxation ... might be valuable additions to treatment programs for rheumatoid arthritis. Ringing in the Ears (Tinnitus) Only a few ...

  16. Relaxation techniques for stress

    MedlinePlus

    ... problems such as high blood pressure, stomachaches, headaches, anxiety, and depression. Using relaxation techniques can help you feel calm. These exercises can also help you manage stress and ease ...

  17. Arrested Hematopoiesis and Vascular Relaxation Defects in Mice with a Mutation in Dhfr

    PubMed Central

    Thoms, Julie A. I.; Knezevic, Kathy; Liu, Jia Jenny; Glaros, Elias N.; Thai, Thuan; Qiao, Qiao; Campbell, Heather; Packham, Deborah; Huang, Yizhou; Papathanasiou, Peter; Tunningley, Robert; Whittle, Belinda; Yeung, Amanda W. S.; Chandrakanthan, Vashe; Hesson, Luke; Chen, Vivien; Wong, Jason W. H.; Purton, Louise E.; Ward, Robyn L.

    2016-01-01

    Dihydrofolate reductase (DHFR) is a critical enzyme in the folate metabolism pathway and also plays a role in regulating nitric oxide (NO) signaling in endothelial cells. Although both coding and noncoding mutations with phenotypic effects have been identified in the human DHFR gene, no mouse model is currently available to study the consequences of perturbing DHFR in vivo. In order to identify genes involved in definitive hematopoiesis, we performed a forward genetic screen and produced a mouse line, here referred to as Orana, with a point mutation in the Dhfr locus leading to a Thr136Ala substitution in the DHFR protein. Homozygote Orana mice initiate definitive hematopoiesis, but expansion of progenitors in the fetal liver is compromised, and the animals die between embryonic day 13.5 (E13.5) and E14.5. Heterozygote Orana mice survive to adulthood but have tissue-specific alterations in folate abundance and distribution, perturbed stress erythropoiesis, and impaired endothelium-dependent relaxation of the aorta consistent with the role of DHFR in regulating NO signaling. Orana mice provide insight into the dual roles of DHFR and are a useful model for investigating the role of environmental and dietary factors in the context of vascular defects caused by altered NO signaling. PMID:26830229

  18. Spin relaxation in metallic ferromagnets

    NASA Astrophysics Data System (ADS)

    Berger, L.

    2011-02-01

    The Elliott theory of spin relaxation in metals and semiconductors is extended to metallic ferromagnets. Our treatment is based on the two-current model of Fert, Campbell, and Jaoul. The d→s electron-scattering process involved in spin relaxation is the inverse of the s→d process responsible for the anisotropic magnetoresistance (AMR). As a result, spin-relaxation rate 1/τsr and AMR Δρ are given by similar formulas, and are in a constant ratio if scattering is by solute atoms. Our treatment applies to nickel- and cobalt-based alloys which do not have spin-up 3d states at the Fermi level. This category includes many of the technologically important magnetic materials. And we show how to modify the theory to apply it to bcc iron-based alloys. We also treat the case of Permalloy Ni80Fe20 at finite temperature or in thin-film form, where several kinds of scatterers exist. Predicted values of 1/τsr and Δρ are plotted versus resistivity of the sample. These predictions are compared to values of 1/τsr and Δρ derived from ferromagnetic-resonance and AMR experiments in Permalloy.

  19. Stress relaxation in viscous soft spheres.

    PubMed

    Boschan, Julia; Vasudevan, Siddarth A; Boukany, Pouyan E; Somfai, Ellák; Tighe, Brian P

    2017-10-04

    We report the results of molecular dynamics simulations of stress relaxation tests in athermal viscous soft sphere packings close to their unjamming transition. By systematically and simultaneously varying both the amplitude of the applied strain step and the pressure of the initial condition, we access both linear and nonlinear response regimes and control the distance to jamming. Stress relaxation in viscoelastic solids is characterized by a relaxation time τ* that separates short time scales, where viscous loss is substantial, from long time scales, where elastic storage dominates and the response is essentially quasistatic. We identify two distinct plateaus in the strain dependence of the relaxation time, one each in the linear and nonlinear regimes. The height of both plateaus scales as an inverse power law with the distance to jamming. By probing the time evolution of particle velocities during relaxation, we further identify a correlation between mechanical relaxation in the bulk and the degree of non-affinity in the particle velocities on the micro scale.

  20. Responsive, di-metallic lanthanide complexes of a piperazine-bridged bis-macrocyclic ligand: modulation of visible luminescence and proton relaxivity.

    PubMed

    Andrews, Michael; Amoroso, Angelo J; Harding, Lindsay P; Pope, Simon J A

    2010-04-14

    The synthesis of a new functionalised bis-macrocyclic ligand (L1) is described together with the corresponding Ln(III) complexes, Ln(2)- (Ln = Gd(III), Eu(III)). Phosphorescence measurements on Gd(2)- at 77 K allowed the ligand-centred triplet state ((3)pi-pi*) to be estimated at ca. 28500 cm(-1). Steady state and time-resolved measurements confirmed emission from the f-centred excited state ((5)D(0)) for Eu(2)-. (1)H NMRD profiles revealed the longitudinal proton relaxivity (r(1)) of Gd(2)- to be 8.3 mM(-1)s(-1)(30 MHz, 25 degrees C). The interaction of Cu(II) and Hg(II) with the lanthanide complexes was probed using luminescence and relaxivity measurements. Addition of Cu(II) (10 eq.) resulted in quenching of the Eu(III) emission, but no increase in r(1) of the Gd(III) dimer. Addition of Hg(II) (10 eq.) caused changes to the hypersensitive emission bands of Eu(III) together with an increase in r(1) of Gd(2)- to be 10.3 mM(-1)s(-1)(30 MHz, 25 degrees C) suggesting a net increase in hydration at the Gd(III) centres.

  1. A comparison of somatic relaxation and EEG activity in classical progressive relaxation and transcendental meditation.

    PubMed

    Warrenburg, S; Pagano, R R; Woods, M; Hlastala, M

    1980-03-01

    Oxygen consumption, electroencephalogram (EEG), and four other measures of somatic relaxation were monitored in groups of long-term practitioners of classical Jacobson's progressive relaxation (PR) and Transcendental Meditation (TM) and also in a group of novice PR trainees. All subjects (1) practiced relaxation or meditation (treatment), (2) sat with eyes closed (EC control), and (3) read from a travel book during two identical sessions on different days. EEG findings indicated that all three groups remained primarily awake during treatment and EC control and that several subjects in each group displayed rare theta (5-7 Hz) waveforms. All three groups demonstrated similar decrements in somatic activity during treatment and EC control which were generally of small magnitude (e. g., 2-5% in oxygen consumption). These results supported the "relaxation response" model for state changes in somatic relaxation for techniques practiced under low levels of stress but not the claim that the relaxation response produced a hypometabolic state. Despite similar state effects, the long-term PR group manifested lower levels of somatic activity across all conditions compared to both novice PR and long-term TM groups. We concluded that PR causes a generalized trait of somatic relaxation which is manifested in a variety of settings and situations. Two likely explanations for this trait were discussed: (1) PR practitioners are taught to generalize relaxation to daily activities, and/or (2) according to a "multiprocess model," PR is a "somatic technique," which should produce greater somatic relaxation than does TM, a "cognitive technique." Further research is required to elucidate these possibilities.

  2. Suxiao Jiuxin Pill Induces Potent Relaxation and Inhibition on Contraction in Human Artery and the Mechanism

    PubMed Central

    Bai, Xiao-Yan; Zhang, Ping; Yang, Qin; Liu, Xiao-Cheng; Wang, Jun; Tong, Yong-Ling; Xiong, Song-Jin; Liu, Li-Hua; Wang, Lei; He, Guo-Wei

    2014-01-01

    Suxiao Jiuxin Pill, a compound Chinese traditional medicine with main components of tetramethylpyrazine and borneol, is widely used for antiangina treatment in China but its pharmacological effect on human blood vessels is unknown. We investigated the effect and possible mechanism of SJP in the human internal mammary artery (IMA, n = 78) taken from patients undergoing coronary surgery. SJP caused full relaxation in KCl- (99.4 ± 10.5%, n = 6) and U46619- (99.9 ± 5.6%, n = 6) contracted IMA. Pretreatment of IMA with plasma concentrations of SJP (1 mg/mL), calculated from the plasma concentration of its major component borneol, significantly depressed the maximal contraction to KCl (from 35.8 ± 6.0 mN to 12.6 ± 5.6 mN, P = 0.03) and U46619 (from 19.4 ± 2.9 mN to 5.7 ± 2.4 mN, P = 0.007) while SJP at 10 mg/mL abolished the subsequent contraction. Endothelium denudation and inhibition of eNOS significantly altered the SJP-induced relaxation without changes of eNOS expression. We conclude that SJP has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors in human arteries. The vasorelaxation involves both endothelium-dependent and -independent mechanisms. Thus, the effect of SJP on human arteries demonstrated in this study may prove to be particularly important in vasorelaxing therapy in cardiovascular disease. PMID:24808920

  3. Relaxation in quantum glasses

    NASA Astrophysics Data System (ADS)

    Ancona Torres, Carlos E.

    The Ising model in transverse field provides the simplest description of a quantum glass. I study two systems that are realizations of the Ising model in transverse field, LiHoxY1-- xF4 and Rb1-- x(NH4)xH2PO 4. In the spin glass LiHoxY1-- xF4, applying a magnetic field Ht transverse to the Ising direction introduces tunneling between the bare Ising eigenstates. In addition, the coupling between the transverse dipolar interaction and the transverse field introduces entanglement or tunable random fields depending on the concentration. By comparing the classical and quantum transitions in LiHo0.198Y0.802F4 and LiHo 0.167Y0.833F4, I characterize the crossover from random field dominated behavior in the 19.8% sample to entanglement dominated behavior in the 16.7% sample. The quantum transition in the 19.8% sample is dominated by the limit on its correlation length caused by the random fields, while the dominant effect in the 16.7% sample is the enhanced tunneling rate introduced by entanglement. The proton glass Rb1--x(NH 4)xH2PO4 relaxes through tunneling of protons in the hydrogen bonds of the crystal, yielding an effective Ising model in transverse field. Since this field cannot be tuned directly, I combine bulk dielectric susceptibility measurements with neutron Compton scattering measurements of the local tunneling potential in two different concentrations, x = 35% and 72%. I find that tunneling drives the fastest relaxation processes at temperatures as high as 20 K and explicitly calculate the tunneling rate from the tunneling potential of the hydrogen bond. Moreover, the structural mechanism for the glassy relaxation allows a real-space picture of the relaxation dynamics to be correlated to the free energy description of aging. I find that the glassy relaxation is driven by the sequential diffusion of defects called Takagi configurations with a classical to quantum crossover in the relaxation at 3 K. I relate the relaxation rate to the quantum action of tunneling

  4. Vascular endothelial dysfunction associated with elevated serum homocysteine levels in rat adjuvant arthritis: effect of vitamin E administration.

    PubMed

    Can, Cenk; Cinar, Mehtap G; Koşay, Sezen; Evinç, Akgün

    2002-06-14

    We aimed to study the alterations in serum homocysteine levels and endothelium-dependent and -independent vascular relaxant responses in adjuvant-induced arthritis of the rat and to determine the effects of vitamin E administration on these changes. Arthritis was induced by a single intradermal injection of Freund's complete adjuvant into the paw. 26 days after the induction of arthritis, serum homocysteine levels and relaxant responses to acetylcholine and sodiumnitroprusside in thoracic aortas were evaluated. The relaxant responses to acetylcholine were decreased in aortas from arthritic rats, whereas the responses to sodiumnitroprusside were not significantly different when compared to the aortas from control rats. A significant increase was observed in serum homocysteine levels of the arthritic rats in comparison to those of controls. Vitamin E administration (100 mg/kg/day, i.m. for 26 days) to arthritic rats resulted in a significant increase in endothelium-dependent aortic responses to acetylcholine and a significant decrease in serum homocysteine levels with respect to the non-treated arthritic rats. However, in healthy rats, vitamin E treatment significantly decreased the acetylcholine-induced relaxant responses. We conclude that adjuvant-induced arthritis in the rat is associated with increased serum homocysteine levels and this is accompanied by a reduction in endothelium-dependent vascular responses in the thoracic aortas. Vitamin E treatment leads to normalization of the increased serum homocysteine levels and improves the endothelium-dependent relaxant responses in this experimental model.

  5. Interaction between Advanced Glycation End Products Formation and Vascular Responses in Femoral and Coronary Arteries from Exercised Diabetic Rats

    PubMed Central

    Delbin, Maria A.; Davel, Ana Paula C.; Couto, Gisele Kruger; de Araújo, Gustavo G.; Rossoni, Luciana Venturini; Antunes, Edson; Zanesco, Angelina

    2012-01-01

    rats, however, a massive production of AGEs still affecting relaxing responses possibly involving other endothelium-dependent vasodilator agents, mainly in coronary artery. PMID:23285277

  6. Collection Development: Relaxation & Meditation, September 1, 2010

    ERIC Educational Resources Information Center

    Lettus, Dodi

    2010-01-01

    One of the first books to document the relationship between stress and physical and emotional health was "The Relaxation Response" by Herbert Benson, M.D., with Miriam Z. Klipper. Originally published in 1975, the book grew out of Benson's observations as a cardiologist and his research as a fellow at Harvard Medical School. Benson's study of…

  7. Collection Development: Relaxation & Meditation, September 1, 2010

    ERIC Educational Resources Information Center

    Lettus, Dodi

    2010-01-01

    One of the first books to document the relationship between stress and physical and emotional health was "The Relaxation Response" by Herbert Benson, M.D., with Miriam Z. Klipper. Originally published in 1975, the book grew out of Benson's observations as a cardiologist and his research as a fellow at Harvard Medical School. Benson's study of…

  8. Dielectric relaxation and magnetodielectric response in DyMn{sub 0.5}Cr{sub 0.5}O{sub 3}

    SciTech Connect

    Yuan, B.; Yang, J. Zuo, X. Z.; Zhu, X. B.; Dai, J. M.; Song, W. H.; Kan, X. C.; Zu, L.; Sun, Y. P.

    2015-09-28

    We investigate the structural, magnetic, and magnetodielectric properties of DyMn{sub 0.5}Cr{sub 0.5}O{sub 3}. The sample can be indexed with an orthorhombic phase with B site disordered space group Pbnm. The valence state of both Mn and Cr ions are suggested to be +3 based on the results of x-ray photoelectron spectroscopy. Two thermally excited dielectric relaxation at temperatures T{sub N2} < T< 300 K and large magnetodielectric effect (MDC = 20%–30%) due to the disordered arrangement of Mn{sup 3+}/Cr{sup 3+} ions associated with electron hopping between them are observed. The absence of any noticeable magnetoresistance effect (MR < 0.5%) demonstrates that the observed magnetodielectric effect is an intrinsic behavior. These results suggest that DyMn{sub 0.5}Cr{sub 0.5}O{sub 3} is a magnetodielectric compound, whose dielectric properties are dependence of the applied magnetic field, which exhibits such effects near room temperature and holds great promise for future device applications.

  9. Long-Term Psychosomatic Effects of Biofeedback vs. Relaxation Training.

    ERIC Educational Resources Information Center

    Nowlis, David P.; Borzone, Ximena C.

    Differences were compared in the short-term and long-term responses of subjects with headache, insomnia, or hypertension to biofeedback training, relaxation, or a combination of both. Headache sufferers, insomniacs, and hypertensives were randomly assigned in equal numbers to biofeedback, relaxation training or a record-keeping control. Over 2…

  10. Long-Term Psychosomatic Effects of Biofeedback vs. Relaxation Training.

    ERIC Educational Resources Information Center

    Nowlis, David P.; Borzone, Ximena C.

    Differences were compared in the short-term and long-term responses of subjects with headache, insomnia, or hypertension to biofeedback training, relaxation, or a combination of both. Headache sufferers, insomniacs, and hypertensives were randomly assigned in equal numbers to biofeedback, relaxation training or a record-keeping control. Over 2…

  11. Nonlocal and collective relaxation in stellar systems

    NASA Technical Reports Server (NTRS)

    Weinberg, Martin D.

    1993-01-01

    The modal response of stellar systems to fluctuations at large scales is presently investigated by means of analytic theory and n-body simulation; the stochastic excitation of these modes is shown to increase the relaxation rate even for a system which is moderately far from instability. The n-body simulations, when designed to suppress relaxation at small scales, clearly show the effects of large-scale fluctuations. It is predicted that large-scale fluctuations will be largest for such marginally bound systems as forming star clusters and associations.

  12. Relaxation in Physical Education Curricula.

    ERIC Educational Resources Information Center

    Coville, Claudia A.

    1979-01-01

    A theoretical framework for incorporating relaxation instruction in the physical education curriculum is presented based on the assumption that relaxation is a muscular-skeletal skill benefitting general motor skill acquisition. Theoretical principles, a definition of relaxation, and an analysis of stages of skill development are also used in the…

  13. Reduced vascular responses to soluble guanylyl cyclase but increased sensitivity to sildenafil in female rats with type 2 diabetes.

    PubMed

    Goulopoulou, Styliani; Hannan, Johanna L; Matsumoto, Takayuki; Ogbi, Safia; Ergul, Adviye; Webb, R Clinton

    2015-07-15

    Impaired nitric oxide (NO), soluble guanylyl cyclase (sGC), and cyclic guanosine monophosphate (cGMP) signaling (NO-sGC-cGMP) has been implicated in the pathogenesis of diabetic vascular dysfunction. Efforts to directly target this signaling have led to the development of sGC agonists that activate the heme group of sGC (stimulators) or preferentially activate sGC when the heme is oxidized (activators). In this study, we hypothesized that resistance arteries from female rats with spontaneous type 2 diabetes (Goto-Kakizaki rats, GK) would have reduced vasodilatory responses to heme-dependent sGC activation and increased responses to heme-independent sGC activation compared with control rats (Wistar). Endothelium-dependent and -independent relaxation was assessed in isolated segments from mesenteric resistance arteries (MA) mounted in a wire myograph. GK MA had reduced responses to acetylcholine (pEC50: 7.96 ± 0.06 vs. 7.66 ± 0.05, P < 0.05) and sodium nitroprusside (pEC50: 8.34 ± 0.05 vs. 7.77 ± 0.04, P < 0.05). There were no group differences in 8-bromoguanosine cGMP-induced relaxation and protein kinase G1 expression (P > 0.05). GK MA had attenuated responses to BAY 41-2272 (heme-dependent sGC stimulator; pEC50: 7.56 ± 0.05 vs. 6.93 ± 0.06, P < 0.05) and BAY 58-2667 (heme-independent sGC activator; pEC50: 10.82 ± 0.07 vs. 10.27 ± 0.08, P < 0.05) and increased sensitivity to sildenafil [phosphodiesterase 5 (PDE5) inhibitor; pEC50: 7.89 ± 0.14 vs. 8.25 ± 0.13, P < 0.05]. Isolated resistance arteries from female rats of reproductive age that spontaneously develop type 2 diabetes have increased sensitivity to PDE5 inhibition and reduced responsiveness to sGC activators and stimulators. Copyright © 2015 the American Physiological Society.

  14. Relaxation from particle production

    NASA Astrophysics Data System (ADS)

    Hook, Anson; Marques-Tavares, Gustavo

    2016-12-01

    We consider using particle production as a friction force by which to implement a "Relaxion" solution to the electroweak hierarchy problem. Using this approach, we are able to avoid superplanckian field excursions and avoid any conflict with the strong CP problem. The relaxation mechanism can work before, during or after inflation allowing for inflationary dynamics to play an important role or to be completely decoupled.

  15. Relaxation from particle production

    SciTech Connect

    Hook, Anson; Marques-Tavares, Gustavo

    2016-12-20

    Here, we consider using particle production as a friction force by which to implement a “Relaxion” solution to the electroweak hierarchy problem. Using this approach, we are able to avoid superplanckian field excursions and avoid any conflict with the strong CP problem. The relaxation mechanism can work before, during or after inflation allowing for inflationary dynamics to play an important role or to be completely decoupled.

  16. Load relaxation of olivine single crystals

    NASA Astrophysics Data System (ADS)

    Cooper, Reid F.; Stone, Donald S.; Plookphol, Thawatchai

    2016-10-01

    Single crystals of ferromagnesian olivine (San Carlos, AZ, peridot; Fo88-90) have been deformed in both uniaxial creep and load relaxation under conditions of ambient pressure, T = 1500°C and pO2 = 10-10 atm; creep stresses were in the range 40 ≤ σ1 (MPa) ≤ 220. The crystals were oriented such that the applied stress was parallel to [011]c, which promotes single slip on the slowest slip system in olivine, (010)[001]. The creep rates at steady state match well the results of earlier investigators, as does the stress sensitivity (a power law exponent of n = 3.6). Dislocation microstructures, including spatial distribution of low-angle (subgrain) boundaries, additionally confirm previous investigations. Inverted primary creep (an accelerating strain rate with an increase in stress) was observed. Load relaxation, however, produced a singular response—a single hardness curve—regardless of the magnitude of creep stress or total accumulated strain preceding relaxation. The log stress versus log strain rate data from load-relaxation and creep experiments overlap to within experimental error. The load-relaxation behavior is distinctly different than that described for other crystalline solids, where the flow stress is affected strongly by work hardening such that a family of distinct hardness curves is generated, which are related by a scaling function. The response of olivine for the conditions studied, we argue, indicates flow that is rate limited by dislocation glide, reflecting specifically a high intrinsic lattice resistance (Peierls stress).

  17. Insulin relaxes bladder via PI3K/AKT/eNOS pathway activation in mucosa: unfolded protein response-dependent insulin resistance as a cause of obesity-associated overactive bladder

    PubMed Central

    Leiria, Luiz O; Sollon, Carolina; Báu, Fernando R; Mónica, Fabíola Z; D’Ancona, Carlos L; De Nucci, Gilberto; Grant, Andrew D; Anhê, Gabriel F; Antunes, Edson

    2013-01-01

    We aimed to investigate the role of insulin in the bladder and its relevance for the development of overactive bladder (OAB) in insulin-resistant obese mice. Bladders from male individuals who were involved in multiple organ donations were used. C57BL6/J mice were fed with a high-fat diet for 10 weeks to induce insulin-resistant obesity. Concentration–response curves to insulin were performed in human and mouse isolated mucosa-intact and mucosa-denuded bladders. Cystometric study was performed in terminally anaesthetized mice. Western blot was performed in bladders to detect phosphorylated endothelial NO synthase (eNOS) (Ser1177) and the phosphorylated protein kinase AKT (Ser473), as well as the unfolded protein response (UPR) markers TRIB3, CHOP and ATF4. Insulin (1–100 nm) produced concentration-dependent mouse and human bladder relaxations that were markedly reduced by mucosal removal or inhibition of the PI3K/AKT/eNOS pathway. In mouse bladders, insulin produced a 3.0-fold increase in cGMP levels (P < 0.05) that was prevented by PI3K/AKT/eNOS pathway inhibition. Phosphoinositide 3-kinase (PI3K) inhibition abolished insulin-induced phosphorylation of AKT and eNOS in bladder mucosa. Obese mice showed greater voiding frequency and non-voiding contractions, indicating overactive detrusor smooth muscle. Insulin failed to relax the bladder or to increase cGMP in the obese group. Insulin-stimulated AKT and eNOS phosphorylation in mucosa was also impaired in obese mice. The UPR markers TRIB3, CHOP and ATF4 were increased in the mucosa of obese mice. The UPR inhibitor 4-phenyl butyric acid normalized all the functional and molecular parameters in obese mice. Our data show that insulin relaxes human and mouse bladder via activation of the PI3K/AKT/eNOS pathway in the bladder mucosa. Endoplasmic reticulum stress-dependent insulin resistance in bladder contributes to OAB in obese mice. PMID:23478138

  18. Insulin relaxes bladder via PI3K/AKT/eNOS pathway activation in mucosa: unfolded protein response-dependent insulin resistance as a cause of obesity-associated overactive bladder.

    PubMed

    Leiria, Luiz O; Sollon, Carolina; Báu, Fernando R; Mónica, Fabíola Z; D'Ancona, Carlos L; De Nucci, Gilberto; Grant, Andrew D; Anhê, Gabriel F; Antunes, Edson

    2013-05-01

    We aimed to investigate the role of insulin in the bladder and its relevance for the development of overactive bladder (OAB) in insulin-resistant obese mice. Bladders from male individuals who were involved in multiple organ donations were used. C57BL6/J mice were fed with a high-fat diet for 10 weeks to induce insulin-resistant obesity. Concentration-response curves to insulin were performed in human and mouse isolated mucosa-intact and mucosa-denuded bladders. Cystometric study was performed in terminally anaesthetized mice. Western blot was performed in bladders to detect phosphorylated endothelial NO synthase (eNOS) (Ser1177) and the phosphorylated protein kinase AKT (Ser473), as well as the unfolded protein response (UPR) markers TRIB3, CHOP and ATF4. Insulin (1-100 nm) produced concentration-dependent mouse and human bladder relaxations that were markedly reduced by mucosal removal or inhibition of the PI3K/AKT/eNOS pathway. In mouse bladders, insulin produced a 3.0-fold increase in cGMP levels (P < 0.05) that was prevented by PI3K/AKT/eNOS pathway inhibition. Phosphoinositide 3-kinase (PI3K) inhibition abolished insulin-induced phosphorylation of AKT and eNOS in bladder mucosa. Obese mice showed greater voiding frequency and non-voiding contractions, indicating overactive detrusor smooth muscle. Insulin failed to relax the bladder or to increase cGMP in the obese group. Insulin-stimulated AKT and eNOS phosphorylation in mucosa was also impaired in obese mice. The UPR markers TRIB3, CHOP and ATF4 were increased in the mucosa of obese mice. The UPR inhibitor 4-phenyl butyric acid normalized all the functional and molecular parameters in obese mice. Our data show that insulin relaxes human and mouse bladder via activation of the PI3K/AKT/eNOS pathway in the bladder mucosa. Endoplasmic reticulum stress-dependent insulin resistance in bladder contributes to OAB in obese mice.

  19. The GPR55 agonist lysophosphatidylinositol relaxes rat mesenteric resistance artery and induces Ca2+ release in rat mesenteric artery endothelial cells

    PubMed Central

    AlSuleimani, Y M; Hiley, C R

    2015-01-01

    Background and Purpose Lysophosphatidylinositol (LPI), a lipid signalling molecule, activates GPR55 and elevates intracellular Ca2+. Here, we examine the actions of LPI in the rat resistance mesenteric artery and Ca2+ responses in endothelial cells isolated from the artery. Experimental Approach Vascular responses were studied using wire myographs. Single-cell fluorescence imaging was performed using a MetaFluor system. Hypotensive effects of LPI were assessed using a Biopac system. Key Results In isolated arteries, LPI-induced vasorelaxation was concentration- and endothelium-dependent and inhibited by CID 16020046, a GPR55 antagonist. The CB1 receptor antagonist AM 251 had no effect, whereas rimonabant and O-1918 significantly potentiated LPI responses. Vasorelaxation was reduced by charybdotoxin and iberiotoxin, alone or combined. LPI decreased systemic arterial pressure. GPR55 is expressed in rat mesenteric artery. LPI caused biphasic elevations of endothelial cell intracellular Ca2+. Pretreatment with thapsigargin or 2-aminoethoxydiphenyl borate abolished both phases. The PLC inhibitor U73122 attenuated the initial phase and enhanced the second phase, whereas the Rho-associated kinase inhibitor Y-27632 abolished the late phase but not the early phase. Conclusions and Implications LPI is an endothelium-dependent vasodilator in the rat small mesenteric artery and a hypotensive agent. The vascular response involves activation of Ca2+-sensitive K+ channels and is not mediated by CB1 receptors, but unexpectedly enhanced by antagonists of the ‘endothelial anandamide’ receptor. In endothelial cells, LPI utilizes PLC-IP3 and perhaps ROCK-RhoA pathways to elevate intracellular Ca2+. Overall, these findings support an endothelial site of action for LPI and suggest a possible role for GPR55 in vasculature. PMID:25652040

  20. Pharmacological analysis of hemodynamic responses to Lachesis muta (South American bushmaster) snake venom in anesthetized rats.

    PubMed

    Dias, Lourdes; Rodrigues, Mariana A P; Inoue, Bruna R; Rodrigues, Renata L; Rennó, André L; de Souza, Valéria B; Torres-Huaco, Frank D; Sousa, Norma C; Stroka, Alessandra; Melgarejo, Anibal R; Hyslop, Stephen

    2016-12-01

    In this work, we examined some mechanisms involved in the hypotension caused by Lachesis muta (South American bushmaster) venom in anesthetized rats. Venom (1.5 mg/kg, i.v.) caused immediate hypotension that was maximal after 5 min and gradually returned to baseline over 60 min. Pretreatment of rats with the non-selective nitric oxide synthase (NOS) inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) did not attenuate the early phase of venom-induced hypotension, but abolished the recovery phase and resulted in rapid death; a similar effect was observed with the soluble guanylate cyclase (sGC) inhibitor ODQ. In contrast, the hemodynamic responses to venom were not attenuated by the non-selective NOS inhibitor N(G)-monomethyl-L-arginine, the inducible NOS inhibitor aminoguanidine, the phosphodiesterase 5 inhibitor sildenafil, the adenylate cyclase (AC) inhibitor SQ-22.536, the non-selective muscarinic receptor antagonist atropine, the bradykinin B2 receptor antagonist HOE-140 and the non-selective cyclooxygenase inhibitor indomethacin. Preincubation of venom with the PLA2 inhibitor pBPB had no effect on the immediate hypotension but tended to improve the recovery phase. Neither AEBSF (a serine proteinase inhibitor) nor EDTA (a metalloproteinase inhibitor) prevented the venom-induced hypotension, but AEBSF and not EDTA protected against the lethality of a high dose (3.0 mg/kg, i.v.). There were no marked changes in the ECG parameters with the various treatments, except with L-NAME and ODQ that increased the RR interval. Pulmonary thrombus formation was markedly enhanced by L-NAME and ODQ, and to a lesser extent by pBPB, especially in small vessels, whereas AEBSF and EDTA inhibited thrombus formation. Venom relaxed phenylephrine-precontracted thoracic aorta and pulmonary artery in vitro, with the latter being more sensitive. The relaxation was endothelium-dependent and was inhibited by ODQ but not by H-89, a protein kinase A (PKA) inhibitor. Together, these

  1. Progressive muscle relaxation, yoga stretching, and ABC relaxation theory.

    PubMed

    Ghoncheh, Shahyad; Smith, Jonathan C

    2004-01-01

    This study compared the psychological effects of progressive muscle relaxation (PMR) and yoga stretching (hatha) exercises. Forty participants were randomly divided into two groups and taught PMR or yoga stretching exercises. Both groups practiced once a week for five weeks and were given the Smith Relaxation States Inventory before and after each session. As hypothesized, practitioners of PMR displayed higher levels of relaxation states (R-States) Physical Relaxation and Disengagement at Week 4 and higher levels of Mental Quiet and Joy as a posttraining aftereffect at Week 5. Contrary to what was hypothesized, groups did not display different levels of R-States Energized or Aware. Results suggest the value of supplementing traditional somatic conceptualizations of relaxation with the psychological approach embodied in ABC relaxation theory. Clinical and research implications are discussed.

  2. Changes in abdominal aortic diameter in response to the cold pressor test and nitroglycerin: a new noninvasive model for the assessment of endothelial-dependent and endothelial-independent vascular relaxation.

    PubMed

    Chandraratna, Premindra Anthony N; Wijegunaratne, Kanishka; Farag, Kameel F; Nimalasuriya, Anoshie R; Mathews, Sajen J

    2009-11-01

    Coronary vascular responses to the cold pressor test (CPT) have been shown to parallel changes caused by infusion of acetylcholine. Whereas the CPT is a method of assessing endothelial-dependent vasodilation, nitroglycerin produces endothelial-independent vasodilation. We performed histological studies on autopsy specimens of abdominal aorta and demonstrated that it is predominantly muscular artery. To test the hypothesis that vasodilatory responses of the abdominal aorta to interventions would parallel those of peripheral vessels, 33 normal males without hypertension, diabetes, or hyperlipidemia, and 10 younger male smokers had ultrasound imaging of the abdominal aorta conducted in the control state, 2 minutes after immersion of the hand in cold water and 10 minutes after rewarming the hand (i.e., cold pressor test). The internal diameter of the abdominal aorta at the onset of the QRS complex was determined for each intervention by averaging 4 beats. It was found that the cold pressor test and nitroglycerin resulted in similar degrees of dilation of the abdominal aorta in nonsmoking subjects, and that these responses were attenuated in smokers. Thus, both endothelial-dependent and endothelial-independent vascular relaxation were impaired in smokers.

  3. Influence of acute pancreatitis on the in vitro responsiveness of rat mesenteric and pulmonary arteries

    PubMed Central

    Camargo, Enilton A; Delbin, Maria Andréia; Ferreira, Tatiane; Landucci, Elen CT; Antunes, Edson; Zanesco, Angelina

    2008-01-01

    Background Acute pancreatitis is an inflammatory disease characterized by local tissue injury and systemic inflammatory response leading to massive nitric oxide (NO) production and haemodynamic disturbances. Therefore, the aim of this work was to evaluate the vascular reactivity of pulmonary and mesenteric artery rings from rats submitted to experimental pancreatitis. Male Wistar rats were divided into three groups: saline (SAL); tauracholate (TAU) and phospholipase A2 (PLA2). Pancreatitis was induced by administration of TAU or PLA2 from Naja mocambique mocambique into the common bile duct of rats, and after 4 h of duct injection the animals were sacrificed. Concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP) and phenylephrine (PHE) in isolated mesenteric and pulmonary arteries were obtained. Potency (pEC50) and maximal responses (EMAX) were determined. Blood samples were collected for biochemical analysis. Results In mesenteric rings, the potency for ACh was significantly decreased from animals treated with TAU (about 4.2-fold) or PLA2 (about 6.9-fold) compared to saline group without changes in the maximal responses. Neither pEC50 nor EMAX values for Ach were altered in pulmonary rings in any group. Similarly, the pEC50 and the EMAX values for SNP were not changed in both preparations in any group. The potency for PHE was significantly decreased in rat mesenteric and pulmonary rings from TAU group compared to SAL group (about 2.2- and 2.69-fold, for mesenteric and pulmonary rings, respectively). No changes were seen in the EMAX for PHE. The nitrite/nitrate (NOx-) levels were markedly increased in animals submitted to acute pancreatitis as compared to SAL group, approximately 76 and 68% in TAU and PLA2 protocol, respectively. Conclusion Acute pancreatitis provoked deleterious effects in endothelium-dependent relaxing response for ACh in mesenteric rings that were strongly associated with high plasma NOx- levels as consequence of

  4. Differentiable McCormick relaxations

    DOE PAGES

    Khan, Kamil A.; Watson, Harry A. J.; Barton, Paul I.

    2016-05-27

    McCormick's classical relaxation technique constructs closed-form convex and concave relaxations of compositions of simple intrinsic functions. These relaxations have several properties which make them useful for lower bounding problems in global optimization: they can be evaluated automatically, accurately, and computationally inexpensively, and they converge rapidly to the relaxed function as the underlying domain is reduced in size. They may also be adapted to yield relaxations of certain implicit functions and differential equation solutions. However, McCormick's relaxations may be nonsmooth, and this nonsmoothness can create theoretical and computational obstacles when relaxations are to be deployed. This article presents a continuously differentiablemore » variant of McCormick's original relaxations in the multivariate McCormick framework of Tsoukalas and Mitsos. Gradients of the new differentiable relaxations may be computed efficiently using the standard forward or reverse modes of automatic differentiation. Furthermore, extensions to differentiable relaxations of implicit functions and solutions of parametric ordinary differential equations are discussed. A C++ implementation based on the library MC++ is described and applied to a case study in nonsmooth nonconvex optimization.« less

  5. Differentiable McCormick relaxations

    SciTech Connect

    Khan, Kamil A.; Watson, Harry A. J.; Barton, Paul I.

    2016-05-27

    McCormick's classical relaxation technique constructs closed-form convex and concave relaxations of compositions of simple intrinsic functions. These relaxations have several properties which make them useful for lower bounding problems in global optimization: they can be evaluated automatically, accurately, and computationally inexpensively, and they converge rapidly to the relaxed function as the underlying domain is reduced in size. They may also be adapted to yield relaxations of certain implicit functions and differential equation solutions. However, McCormick's relaxations may be nonsmooth, and this nonsmoothness can create theoretical and computational obstacles when relaxations are to be deployed. This article presents a continuously differentiable variant of McCormick's original relaxations in the multivariate McCormick framework of Tsoukalas and Mitsos. Gradients of the new differentiable relaxations may be computed efficiently using the standard forward or reverse modes of automatic differentiation. Furthermore, extensions to differentiable relaxations of implicit functions and solutions of parametric ordinary differential equations are discussed. A C++ implementation based on the library MC++ is described and applied to a case study in nonsmooth nonconvex optimization.

  6. Renal T(*)(2) perfusion using an iron oxide nanoparticle contrast agent--influence of T(1) relaxation on the first-pass response.

    PubMed

    Bjørnerud, Atle; Johansson, Lars O; Ahlström, Håkan K

    2002-02-01

    Quantitative perfusion measurements require accurate knowledge of the correlation between first-pass signal changes and the corresponding tracer concentration in tissue. In the present study, a detailed analysis of first-pass renal cortical changes in T(1) and T(*)(2) following bolus injection of the iron oxide nanoparticle NC100150 Injection was investigated in a pig model using a double-echo gradient-echo sequence. The estimated change in 1/T(*)(2) during first pass calculated from single-echo sequences was compared to the true double-echo-derived 1/T(*)(2) curves. Using a single-echo (TE = 6 ms) spoiled gradient-echo sequence, the first-pass 1/T(*)(2) response following a bolus injection of 1 mg Fe/kg of NC100150 Injection was significantly underestimated due to counteracting T(1) effects. Signal response simulations showed that the relative error in the first-pass response decreased with increasing TE and contrast agent dose. However, both the maximum TE and the maximum dose are limited by excessive cortical signal loss, and the maximum TE is further limited by high temporal resolution requirements. The problem of T(1) contamination can effectively be overcome by using a double-echo gradient-echo sequence. This yields a first-pass response that truly reflects the tissue tracer concentration, which is a critical requirement for quantitative renal perfusion assessment.

  7. Grueneisen Relaxation Photoacoustic Microscopy

    NASA Astrophysics Data System (ADS)

    Wang, Lidai; Zhang, Chi; Wang, Lihong V.

    2014-10-01

    The temperature-dependent property of the Grueneisen parameter has been employed in photoacoustic imaging mainly to measure tissue temperature. Here we explore this property using a different approach and develop Grueneisen relaxation photoacoustic microscopy (GR-PAM), a technique that images nonradiative absorption with confocal optical resolution. GR-PAM sequentially delivers two identical laser pulses with a microsecond-scale time delay. The first laser pulse generates a photoacoustic signal and thermally tags the in-focus absorbers. When the second laser pulse excites the tagged absorbers within the thermal relaxation time, a photoacoustic signal stronger than the first one is produced, owing to the temperature dependence of the Grueneisen parameter. GR-PAM detects the amplitude difference between the two colocated photoacoustic signals, confocally imaging the nonradiative absorption. We greatly improved axial resolution from 45 μm to 2.3 μm and, at the same time, slightly improved lateral resolution from 0.63 μm to 0.41 μm. In addition, the optical sectioning capability facilitates the measurement of the absolute absorption coefficient without fluence calibration.

  8. Ultrafast Relaxation in Conjugated Polymers

    NASA Astrophysics Data System (ADS)

    Kobayashi, Takayoshi

    The following sections are included: * INTRODUCTION * EXPERIMENTAL * Samples * Femtosecond experimental apparatus * RESULTS AND DISCUSSION * Poly(phenylacetylenes) * Blue-phase PDA-3BCMU * Red-phase PDA-4BCMU * Blue-phase PDA-DFMP * P3MT * P3DT * PTV * RELAXATION MECHANISMS * Review of the previous works * Symmetry of the lower electronic excited states * Primary relaxation processes * Theoretical studies of nonlinear excitations * Mechanism of relaxation in polymers with a weakly nondegenerate ground state (poly(phenylacetylene)s) * Dual peak component with power-law decay * Single-peak component with an exponential decay * Hot self-trapped exciton * Transition to the electron-hole threshold * Transition to a biexciton state * Mechanism of relaxation in polymers with a strongly or moderately nondegenerate ground state * Classifications of polymers * Femtosecond relaxation * Picosecond relaxation * CONCLUSION * Acknowledgments * REFERENCES

  9. Relaxing music for anxiety control.

    PubMed

    Elliott, Dave; Polman, Remco; McGregor, Richard

    2011-01-01

    The purpose of this investigation was to determine the characteristics of relaxing music for anxiety control. Undergraduate students (N=84) were instructed to imagine themselves in an anxiety producing situation while listening to a selection of 30 music compositions. For each composition, level of relaxation, the factors that either enhanced or detracted from its relaxing potential and the emotional labels attached were assessed. Participants were also asked to state which music components (e.g., tempo, melody) were most conducive to relaxation. Additional information was obtained through the use of a focus group of 6 undergraduate music students. This paper presents details on the characteristics of relaxing-music for anxiety control and emotional labels attached to the relaxing compositions. Furthermore, an importance value has been attached to each of the music components under scrutiny, thus providing an indication of which music components should receive greatest attention when selecting music for anxiety control.

  10. ABC relaxation theory and the factor structure of relaxation states, recalled relaxation activities, dispositions, and motivations.

    PubMed

    Smith, J C; Wedell, A B; Kolotylo, C J; Lewis, J E; Byers, K Y; Segin, C M

    2000-06-01

    ABC Relaxation Theory proposes 15 psychological relaxation-related states (R-States): Sleepiness, Disengagement, Physical Relaxation, Mental Quiet, Rested/Refreshed, At Ease/At Peace, Energized, Aware, Joy, Thankfulness and Love, Prayerfulness, Childlike Innocence, Awe and Wonder, Mystery, and Timeless/Boundless/Infinite. The present study summarizes the results of 13 separate factor analyses of immediate relaxation-related states, states associated with recalled relaxation activities, relaxation dispositions, and relaxation motivations on a combined sample of 1,904 individuals (group average ages ranged from 28-40 yr.). Four exploratory factor analyses of Smith Relaxation Inventories yielded 15 items that most consistently and exclusively load (generally at least .70) on six replicated factors. These items included happy, joyful, energized, rested, at peace, warm, limp, silent, quiet, dozing, drowsy, prayerful, mystery, distant, and indifferent. Subsequent factor analyses restricted to these items and specifying six factors were performed on 13 different data sets. Each yielded the same six-factor solution: Factor 1: Centered Positive Affect, Factor 2: Sleepiness, Factor 3: Disengagement, Factor 4: Physical Relaxation, Factor 5: Mental Quiet, and Factor 6: Spiritual. Implications for ABC Relaxation Theory are discussed.

  11. Comet Bursting Through Relaxation

    NASA Astrophysics Data System (ADS)

    Jacobson, Seth A.; Scheeres, D. J.

    2012-10-01

    Comets may be excited and occupy non-principal axis (complex) rotation states for a large fraction of their lifetimes. Many comet nuclei have been identified or are suspected to occupy non-principal axis (complex) rotation [Belton 2005, etc.] as well as have evolvi