Agmatine Induced NO Dependent Rat Mesenteric Artery Relaxation and its Impairment in Salt-Sensitive Hypertension

PubMed Central

Gadkari, Tushar V.; Cortes, Natalie; Madrasi, Kumpal; Tsoukias, Nikolaos M.; Joshi, Mahesh S.

2013-01-01

L-arginine and its decarboxylated product, agmatine are important mediators of NO production and vascular relaxation. However, the underlying mechanisms of their action are not understood. We have investigated the role of arginine and agmatine in resistance vessel relaxation of Sprague-Dawley (SD) and Dahl salt-sensitive hypertensive rats. Second or 3rd-order mesenteric arterioles were cannulated in an organ chamber, pressurized and equilibrated before perfusing intraluminally with agonists. The vessel diameters were measured after mounting on the stage of a microscope fitted with a video camera. The gene expression in Dahl rat vessel homogenates was ascertained by real-time PCR. L-arginine initiated relaxations (EC50, 5.8 ± 0.7 mM; n = 9) were inhibited by arginine decarboxylase (ADC) inhibitor, difluoromethylarginine (DFMA) (EC50, 18.3 ± 1.3 mM; n = 5) suggesting that arginine-induced vessel relaxation was mediated by agmatine formation. Agmatine relaxed the SD rat vessels at significantly lower concentrations (EC50, 138.7 ± 12.1 μM; n = 22), which was compromised by L-NAME (L-NG-Nitroarginine methyl ester, an eNOS inhibitor), RX821002 (α-2 AR antagonist) and pertussis toxin (G-protein inhibitor). The agmatine-mediated vessel relaxation from high salt Dahl rats was abolished as compared to that from normal salt rats (EC50, 143.9 ± 23.4 μM; n = 5). The α-2A AR, α-2B AR and eNOS mRNA expression was downregulated in mesenteric arterioles of high-salt treated Dahl hypertensive rats. These findings demonstrate that agmatine facilitated the relaxation via activation of α-2 adrenergic G-protein coupled receptor and NO synthesis, and this pathway is compromised in salt-sensitive hypertension. PMID:23994446

Agmatine induced NO dependent rat mesenteric artery relaxation and its impairment in salt-sensitive hypertension.

PubMed

Gadkari, Tushar V; Cortes, Natalie; Madrasi, Kumpal; Tsoukias, Nikolaos M; Joshi, Mahesh S

2013-11-30

l-Arginine and its decarboxylated product, agmatine are important mediators of NO production and vascular relaxation. However, the underlying mechanisms of their action are not understood. We have investigated the role of arginine and agmatine in resistance vessel relaxation of Sprague-Dawley (SD) and Dahl salt-sensitive hypertensive rats. Second or 3rd-order mesenteric arterioles were cannulated in an organ chamber, pressurized and equilibrated before perfusing intraluminally with agonists. The vessel diameters were measured after mounting on the stage of a microscope fitted with a video camera. The gene expression in Dahl rat vessel homogenates was ascertained by real-time PCR. l-Arginine initiated relaxations (EC50, 5.8±0.7mM; n=9) were inhibited by arginine decarboxylase (ADC) inhibitor, difluoromethylarginine (DFMA) (EC50, 18.3±1.3mM; n=5) suggesting that arginine-induced vessel relaxation was mediated by agmatine formation. Agmatine relaxed the SD rat vessels at significantly lower concentrations (EC50, 138.7±12.1μM; n=22), which was compromised by l-NAME (l-N(G)-nitroarginine methyl ester, an eNOS inhibitor), RX821002 (α-2 AR antagonist) and pertussis toxin (G-protein inhibitor). The agmatine-mediated vessel relaxation from high salt Dahl rats was abolished as compared to that from normal salt rats (EC50, 143.9±23.4μM; n=5). The α-2A AR, α-2B AR and eNOS mRNA expression was downregulated in mesenteric arterioles of high-salt treated Dahl hypertensive rats. These findings demonstrate that agmatine facilitated the relaxation via activation of α-2 adrenergic G-protein coupled receptor and NO synthesis, and this pathway is compromised in salt-sensitive hypertension. Copyright © 2013 Elsevier Inc. All rights reserved.

HV1 acts as a sodium sensor and promotes superoxide production in medullary thick ascending limb of Dahl salt-sensitive rats.

PubMed

Jin, Chunhua; Sun, Jingping; Stilphen, Carly A; Smith, Susan M E; Ocasio, Hiram; Bermingham, Brent; Darji, Sandip; Guha, Avirup; Patel, Roshan; Geurts, Aron M; Jacob, Howard J; Lambert, Nevin A; O'Connor, Paul M

2014-09-01

We previously characterized a H(+) transport pathway in medullary thick ascending limb nephron segments that when activated stimulated the production of superoxide by nicotinamide adenine dinucleotide phosphate oxidase. Importantly, the activity of this pathway was greater in Dahl salt-sensitive rats than salt-resistant (SS.13(BN)) rats, and superoxide production was enhanced in low Na(+) media. The goal of this study was to determine the molecular identity of this pathway and its relationship to Na(+). We hypothesized that the voltage-gated proton channel, HV1, was the source of superoxide-stimulating H(+) currents. To test this hypothesis, we developed HV1(-/-) null mutant rats on the Dahl salt-sensitive rat genetic background using zinc-finger nuclease gene targeting. HV1 could be detected in medullary thick limb from wild-type rats. Intracellular acidification using an NH4Cl prepulse in 0 sodium/BaCl2 containing media resulted in superoxide production in thick limb from wild-type but not HV1(-/-) rats (P<0.05) and more rapid recovery of intracellular pH in wild-type rats (ΔpHI 0.005 versus 0.002 U/s, P=0.046, respectively). Superoxide production was enhanced by low intracellular sodium (<10 mmol/L) in both thick limb and peritoneal macrophages only when HV1 was present. When fed a high-salt diet, blood pressure, outer medullary renal injury (tubular casts), and oxidative stress (4-hydroxynonenal staining) were significantly reduced in HV1(-/-) rats compared with wild-type Dahl salt-sensitive rats. We conclude that HV1 is expressed in medullary thick ascending limb and promotes superoxide production in this segment when intracellular Na(+) is low. HV1 contributes to the development of hypertension and renal disease in Dahl salt-sensitive rats. © 2014 American Heart Association, Inc.

Korean Solar Salt Ameliorates Colon Carcinogenesis in an AOM/DSS-Induced C57BL/6 Mouse Model.

PubMed

Ju, Jaehyun; Kim, Yeung-Ju; Park, Eui Seong; Park, Kun-Young

2017-06-01

The effects of Korean solar salt on an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon cancer C57BL/6 mouse model were studied. Korean solar salt samples (SS-S, solar salt from S salt field; SS-Yb, solar salt from Yb salt field), nine-time-baked bamboo salt (BS-9x, made from SS-Yb), purified salt (PS), and SS-G (solar salt from Guérande, France) were orally administered at a concentration of 1% during AOM/DSS colon cancer induction, and compared for their protective effects during colon carcinogenesis in C57BL/6 mice. SS-S and SS-Yb suppressed colon length shortening and tumor counts in mouse colons. Histological evaluation by hematoxylin and eosin staining also revealed suppression of tumorigenesis by SS-S. Conversely, PS and SS-G did not show a similar suppressive efficacy as Korean solar salt. SS-S and SS-Yb promoted colon mRNA expression of an apoptosis-related factor and cell-cycle-related gene and suppressed pro-inflammatory factor. SS-Yb baked into BS-9x further promoted these anti-carcinogenic efficacies. Taken together, the results indicate that Korean solar salt, especially SS-S and SS-Yb, exhibited anti-cancer activity by modulating apoptosis- and inflammation-related gene expression during colon carcinogenesis in mice, and bamboo salt baked from SS-Yb showed enhanced anti-cancer functionality.

Salt taste responses of the IXth nerve in Sprague-Dawley rats: lack of sensitivity to amiloride.

PubMed

Kitada, Y; Mitoh, Y; Hill, D L

1998-03-01

To explore characteristics of the salt taste function of taste receptor cells located on the posterior tongue, we recorded electrophysiological responses from the whole glossopharyngeal nerve in Sprague-Dawley (SD) rats. For all salts, relative response magnitudes increased with increased stimulus concentrations (0.2-2.0 M) of NH4+, K+, and Na+ salts. The order of effectiveness of stimulation for Cl- salts was NH4Cl > KCl > NaCl. For sodium salts, relative response magnitudes were anion dependent. Sodium salts with small anions (NaCl, NaSCN, and NaNO3) had a much stronger stimulating effect than sodium salts with large anion groups (Na2SO4, C2H3O2Na, and C6H11O7Na). The responses of the glossopharyngeal nerve to the Na+ salts of NaCl, C2H3O2Na, and C6H11O7Na were not inhibited by the lingual application of the epithelial sodium transport blocker amiloride. This is in contrast to large amiloride sensitivity of the chorda tympani nerve. Amiloride also failed to inhibit the responses to K+ salts (KCl and KC2H3O2) and to NH4Cl. These results demonstrate that taste receptors innervated by the glossopharyngeal nerve in SD rats lack amiloride sensitivity as observed in the glossopharyngeal nerve of spontaneously hypertensive and Wistar-Kyoto rats. Furthermore, the difference between the small-anion group and the large-anion group of Na+ salts in their effectiveness to produce responses in the glossopharyngeal nerve parallels the effects noted for the anion dependence in the portion of the taste response resistant to amiloride in the chorda tympani nerve. Sodium salts with the smaller anion produced the larger responses in both glossopharyngeal and chorda tympani nerves after amiloride.

Dietary salt blunts vasodilation by stimulating epithelial sodium channels in endothelial cells from salt-sensitive Dahl rats.

PubMed

Wang, Zi-Rui; Liu, Hui-Bin; Sun, Ying-Ying; Hu, Qing-Qing; Li, Yu-Xia; Zheng, Wei-Wan; Yu, Chang-Jiang; Li, Xin-Yuan; Wu, Ming-Ming; Song, Bin-Lin; Mu, Jian-Jun; Yuan, Zu-Yi; Zhang, Zhi-Ren; Ma, He-Ping

2018-04-01

Our recent studies show that the reduced activity of epithelial sodium channels (ENaC) in endothelial cells accounts for the adaptation of vasculature to salt in Sprague-Dawley rats. The present study examines a hypothesis that enhanced ENaC activity mediates the loss of vasorelaxation in Dahl salt-sensitive (SS) rats. We used the cell-attached patch-clamp technique to record ENaC activity in split-open mesenteric arteries. Western blot and immunofluorescence staining were used to evaluate the levels of aldosterone, ENaC, eNOS and NO. Blood pressure was measured with the tail-cuff method and the artery relaxation was measured with the wire myograph assay. High-salt (HS) diet significantly increased plasma aldosterone and ENaC activity in the endothelial cells of Dahl SS rats. The endothelium-dependent artery relaxation was blunted by HS challenge in these rats. Amiloride, a potent blocker of ENaC, increased both phosphorylated eNOS and NO and therefore prevented the HS-induced loss of vasorelaxation. As, in SS rats, endogenous aldosterone was already elevated by HS challenge, exogenous aldosterone did not further elevate ENaC activity in the rats fed with HS. Eplerenone, a mineralocorticoid receptor antagonist, attenuated the effects of HS on both ENaC activity and artery relaxation. These data suggest that HS diet blunts artery relaxation and causes hypertension via a pathway associated with aldosterone-dependent activation of ENaC in endothelial cells. This pathway provides one of the mechanisms by which HS causes hypertension in Dahl SS rats. This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc. © 2017 The British Pharmacological Society.

Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats.

PubMed

Walsh, Kathryn R; Kuwabara, Jill T; Shim, Joon W; Wainford, Richard D

2016-01-15

Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P < 0.05]. In these salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P < 0.05; NE+NS: 11.1 ± 1.1; NE+HS: 10.8 ± 0.4). NE infusion did not alter NCC expression in animals maintained on NS; however, dietary sodium-evoked suppression of NCC expression was prevented in animals challenged with NE. Chronic NCC antagonism abolished the salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension. Copyright © 2016 the American Physiological Society.

Sodium bicarbonate loading limits tubular cast formation independent of glomerular injury and proteinuria in dahl salt-sensitive rats.

PubMed

Ray, S C; Patel, B; Irsik, D L; Sun, J; Ocasio, H; Crislip, G R; Jin, C H; Chen, J K; Baban, B; Polichnowski, A J; O'Connor, P M

2018-04-12

Sodium bicarbonate (NaHCO 3 ) slows the decline in kidney function in patients with chronic kidney disease (CKD), yet the mechanisms mediating this effect remain unclear. The Dahl salt-sensitive (SS) rat develops hypertension and progressive renal injury when fed a high salt diet; however, the effect of alkali loading on kidney injury has never been investigated in this model. We hypothesized that 'NaHCO 3 protects from the development of renal injury in Dahl salt-sensitive rats via luminal alkalization which limits the formation of tubular casts, which are a prominent pathological feature in this model. To examine this hypothesis, we determined blood pressure and renal injury responses in Dahl SS rats drinking vehicle (0.1M NaCl) or NaHCO 3 (0.1M) solutions as well as in Dahl SS rats lacking the voltage gated proton channel (Hv1). We found that oral NaHCO 3 reduced tubular NH 4 + production, tubular cast formation and interstitial fibrosis in rats fed a high salt diet for 2 weeks. This effect was independent of changes in blood pressure, glomerular injury or proteinuria and did not associate with changes in renal inflammatory status. We found that null mutation of Hv1 also limited cast formation in Dahl SS rats independent of proteinuria or glomerular injury. As Hv1 is localized to the luminal membrane of TAL, our data, suggest that alkalization of the luminal fluid within this segment limits cast formation in this model. Reduced cast formation, secondary to luminal alkalization within TAL segments may mediate some of the protective effects of alkali loading observed in CKD patients. ©2018 The Author(s).

Moderate (20%) fructose-enriched diet stimulates salt-sensitive hypertension with increased salt retention and decreased renal nitric oxide.

PubMed

Gordish, Kevin L; Kassem, Kamal M; Ortiz, Pablo A; Beierwaltes, William H

2017-04-01

Previously, we reported that 20% fructose diet causes salt-sensitive hypertension. In this study, we hypothesized that a high salt diet supplemented with 20% fructose (in drinking water) stimulates salt-sensitive hypertension by increasing salt retention through decreasing renal nitric oxide. Rats in metabolic cages consumed normal rat chow for 5 days (baseline), then either: (1) normal salt for 2 weeks, (2) 20% fructose in drinking water for 2 weeks, (3) 20% fructose for 1 week, then fructose + high salt (4% NaCl) for 1 week, (4) normal chow for 1 week, then high salt for 1 week, (5) 20% glucose for 1 week, then glucose + high salt for 1 week. Blood pressure, sodium excretion, and cumulative sodium balance were measured. Systolic blood pressure was unchanged by 20% fructose or high salt diet. 20% fructose + high salt increased systolic blood pressure from 125 ± 1 to 140 ± 2 mmHg ( P  < 0.001). Cumulative sodium balance was greater in rats consuming fructose + high salt than either high salt, or glucose + high salt (114.2 ± 4.4 vs. 103.6 ± 2.2 and 98.6 ± 5.6 mEq/Day19; P  < 0.05). Sodium excretion was lower in fructose + high salt group compared to high salt only: 5.33 ± 0.21 versus 7.67 ± 0.31 mmol/24 h; P  < 0.001). Nitric oxide excretion was 2935 ± 256  μ mol/24 h in high salt-fed rats, but reduced by 40% in the 20% fructose + high salt group (2139 ± 178  μ mol /24 hrs P  < 0.01). Our results suggest that fructose predisposes rats to salt-sensitivity and, combined with a high salt diet, leads to sodium retention, increased blood pressure, and impaired renal nitric oxide availability. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

MEDULLARY THICK ASCENDING LIMB BUFFER VASOCONSTRICTION OF RENAL OUTER-MEDULLARY VASA RECTA IN SALT-RESISTANT BUT NOT SALT-SENSITIVE RATS

PubMed Central

O’Connor, Paul M.; Cowley, Allen W.

2013-01-01

We have previously demonstrated that paracrine signaling occurs between medullary thick ascending limb (mTAL) and the contractile pericytes of outer-medullary vasa recta (VR) termed ‘tubular-vascular cross talk’. The aim of the current study was to determine whether tubular-vascular cross talk has a functional effect on vasoconstrictor responses to angiotensin II, and to determine whether this is altered in the Dahl salt-sensitive (SS) rat. Studies were performed on salt-resistant consomic SS.13BN and SS rats using a novel outer medullary tissue strip preparation in which freshly isolated VR within VR bundles were perfused either alone or in combination with nearby mTAL. In VR from SS.13BN rats, angiotensin II (1μM) increased VR bundle intracellular Ca2+ concentration ([Ca2+]VR) 19±9nM (n=8) and reduced focal diameter in perfused VR by (−20±7%;n=5). In the presence of nearby mTAL however, [Ca2+]VR (−9±8nM; n=8) and VR diameter (−1±4%, n=7) in SS.13BN rats was unchanged by angiotensin II. In contrast, in Dahl SS rats, angiotensin II resulted in rapid and sustained increase in [Ca2+]VR (89±48 n=7;50±24% n=8) and a reduction in VR diameter of (−17±7;n=7 and −11±4%;n=5) in both isolated VR and VR with nearby mTAL, respectively. In VR with mTAL from SS13BN rats, inhibiton of purinergic receptors resulted in an increase in [Ca2+]VR, indicating purinergic signaling buffers vasoconstriction. Importantly, our in vitro data were able to predict medullary blood flow responses to angiotensin II in SS and SS.13BN rats in vivo. We conclude that paracrine signaling from mTAL buffers angiotensin II vasoconstriction in Dahl salt-resistant SS.13BN rats but not SS rats. PMID:22926950

EVIDENCE OF THE IMPORTANCE OF NOX4 IN PRODUCTION OF HYPERTENSION IN DAHL SALT-SENSITIVE RATS

PubMed Central

Cowley, Allen W.; Yang, Chun; Zheleznova, Nadezhda N.; Staruschenko, Alexander; Kurth, Theresa; Rein, Lisa; Kumar, Vikash; Sadovnikov, Katherine; Dayton, Alex; Hoffman, Matthew; Ryan, Robert P.; Skelton, Meredith M.; Salehpour, Fahimeh; Ranji, Mahsa; Geurts, Aron

2015-01-01

This study reports the consequences of knocking out NADPH oxidase 4 (Nox4) upon the development of hypertension and kidney injury in the Dahl salt-sensitive (SS) rat. Zinc finger nuclease injection of single cell SS embryos was used to create an 8 base-pair frame-shift deletion of Nox4 resulting in a loss of the ~68 kD band in Western blot analysis of renal cortical tissue of the SSNox4−/− rats. SSNox4−/− rats exhibited a significant reduction of salt-induced hypertension compared to SS rats after 21 days of 4.0% NaCl diet (134±5 vs 151±3 mmHg in SS) and a significant reduction of albuminuria, tubular casts, and glomerular injury. Optical fluorescence 3D cryoimaging revealed significantly higher redox ratios (NADH/FAD) in the kidneys of SSNox4−/− rats even when fed the 0.4% NaCl diet indicating greater levels of mitochondrial electron transport chain metabolic activity and reduced oxidative stress compared to SS rats. Prior to the development of hypertension, RNA expression levels of NADPH oxidase subunits Nox2, p67phox, and p22phox were found to be significantly lower (p<0.05) in SSNox4−/− compared to SS rats in the renal cortex. Thus the mutation of Nox4 appears to modify transcription of a number of genes in ways that contribute to the protective effects observed in the SSNox4−/− rats. We conclude that the reduced renal injury and attenuated blood pressure response to high salt in the SSNox4−/− rat could be the result of multiple pathways including gene transcription, mitochondrial energetics, oxidative stress, and protein matrix production impacted by the knock out of Nox4. PMID:26644237

Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling

PubMed Central

Yu, Hao; Yang, Tao; Gao, Peng; Wei, Xing; Zhang, Hexuan; Xiong, Shiqiang; Lu, Zongshi; Li, Li; Wei, Xiao; Chen, Jing; Zhao, Yu; Arendshorst, William J.; Shang, Qianhui; Liu, Daoyan; Zhu, Zhiming

2016-01-01

High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na+ channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC. PMID:27173481

Evidence of the Importance of Nox4 in Production of Hypertension in Dahl Salt-Sensitive Rats.

PubMed

Cowley, Allen W; Yang, Chun; Zheleznova, Nadezhda N; Staruschenko, Alexander; Kurth, Theresa; Rein, Lisa; Kumar, Vikash; Sadovnikov, Katherine; Dayton, Alex; Hoffman, Matthew; Ryan, Robert P; Skelton, Meredith M; Salehpour, Fahimeh; Ranji, Mahsa; Geurts, Aron

2016-02-01

This study reports the consequences of knocking out NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 4 (Nox4) on the development of hypertension and kidney injury in the Dahl salt-sensitive (SS) rat. Zinc finger nuclease injection of single-cell SS embryos was used to create an 8 base-pair frame-shift deletion of Nox4, resulting in a loss of the ≈68 kDa band in Western blot analysis of renal cortical tissue of the knock out of Nox4 in the SS rat (SS(Nox4-/-)) rats. SS(Nox4-/-) rats exhibited a significant reduction of salt-induced hypertension compared with SS rats after 21 days of 4.0% NaCl diet (134±5 versus 151±3 mm Hg in SS) and a significant reduction of albuminuria, tubular casts, and glomerular injury. Optical fluorescence 3-dimensional cryoimaging revealed significantly higher redox ratios (NADH/FAD [reduced nicotinamide adenine dinucleotide/flavin adenine dinucleotide]) in the kidneys of SS(Nox4-/-) rats even when fed the 0.4% NaCl diet, indicating greater levels of mitochondrial electron transport chain metabolic activity and reduced oxidative stress compared with SS rats. Before the development of hypertension, RNA expression levels of Nox subunits Nox2, p67(phox), and p22(phox) were found to be significantly lower (P<0.05) in SS(Nox4-/-) compared with SS rats in the renal cortex. Thus, the mutation of Nox4 seems to modify transcription of several genes in ways that contribute to the protective effects observed in the SS(Nox4-/-) rats. We conclude that the reduced renal injury and attenuated blood pressure response to high salt in the SS(Nox4-/-) rat could be the result of multiple pathways, including gene transcription, mitochondrial energetics, oxidative stress, and protein matrix production impacted by the knock out of Nox4. © 2015 American Heart Association, Inc.

Age-dependent salt hypertension in Dahl rats: fifty years of research.

PubMed

Zicha, J; Dobešová, Z; Vokurková, M; Rauchová, H; Hojná, S; Kadlecová, M; Behuliak, M; Vaněčková, I; Kuneš, J

2012-01-01

Fifty years ago, Lewis K. Dahl has presented a new model of salt hypertension - salt-sensitive and salt-resistant Dahl rats. Twenty years later, John P. Rapp has published the first and so far the only comprehensive review on this rat model covering numerous aspects of pathophysiology and genetics of salt hypertension. When we summarized 25 years of our own research on Dahl/Rapp rats, we have realized the need to outline principal abnormalities of this model, to show their interactions at different levels of the organism and to highlight the ontogenetic aspects of salt hypertension development. Our attention was focused on some cellular aspects (cell membrane function, ion transport, cell calcium handling), intra- and extrarenal factors affecting renal function and/or renal injury, local and systemic effects of renin-angiotensin-aldosterone system, endothelial and smooth muscle changes responsible for abnormal vascular contraction or relaxation, altered balance between various vasoconstrictor and vasodilator systems in blood pressure maintenance as well as on the central nervous and peripheral mechanisms involved in the regulation of circulatory homeostasis. We also searched for the age-dependent impact of environmental and pharmacological interventions, which modify the development of high blood pressure and/or organ damage, if they influence the salt-sensitive organism in particular critical periods of development (developmental windows). Thus, severe self-sustaining salt hypertension in young Dahl rats is characterized by pronounced dysbalance between augmented sympathetic hyperactivity and relative nitric oxide deficiency, attenuated baroreflex as well as by a major increase of residual blood pressure indicating profound remodeling of resistance vessels. Salt hypertension development in young but not in adult Dahl rats can be attenuated by preventive increase of potassium or calcium intake. On the contrary, moderate salt hypertension in adult Dahl rats is

Protective effect of dietary potassium against vascular injury in salt-sensitive hypertension.

PubMed

Kido, Makiko; Ando, Katsuyuki; Onozato, Maristela L; Tojo, Akihiro; Yoshikawa, Masahiro; Ogita, Teruhiko; Fujita, Toshiro

2008-02-01

Hypertensive cardiovascular damage is accelerated by salt loading but counteracted by dietary potassium supplementation. We suggested recently that antioxidant actions of potassium contribute to protection against salt-induced cardiac dysfunction. Therefore, we examined whether potassium supplementation ameliorated cuff-induced vascular injury in salt-sensitive hypertension via suppression of oxidative stress. Four-week-old Dahl salt-sensitive rats were fed a normal-salt (0.3% NaCl), high-salt (8% NaCl), or high-salt plus high-potassium (8% KCl) diet for 5 weeks, and some of the rats fed a high-salt diet were also given antioxidants. One week after the start of the treatments, a silicone cuff was implanted around the femoral artery. Examination revealed increased cuff-induced neointimal proliferation with adventitial macrophage infiltration in arteries from salt-loaded Dahl salt-sensitive rats compared with that in arteries from non-salt-loaded animals (intima/media ratio: 0.471+/-0.070 versus 0.302+/-0.037; P<0.05), associated with regional superoxide overproduction and reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and mRNA overexpression. On the other hand, simultaneous potassium supplementation attenuated salt-induced neointimal hyperplasia (intima/media ratio: 0.205+/-0.012; P<0.001), adventitial macrophage infiltration, superoxide overproduction, and reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and overexpression. Antioxidants, which decrease vascular oxidative stress, also reduced neointima formation induced by salt excess. In conclusion, high-potassium diets seems to have a protective effect against the development of vascular damage induced by salt loading mediated, at least in part, through suppression of the production of reactive oxygen species probably generated by reduced nicotinamide-adenine dinucleotide phosphate oxidase.

Comparative effects of valsartan in combination with cilnidipine or amlodipine on cardiac remodeling and diastolic dysfunction in Dahl salt-sensitive rats.

PubMed

Nagasawa, Kai; Takahashi, Keiji; Matsuura, Natsumi; Takatsu, Miwa; Hattori, Takuya; Watanabe, Shogo; Harada, Eri; Niinuma, Kazumi; Murohara, Toyoaki; Nagata, Kohzo

2015-01-01

Angiotensin receptor blockers (ARBs) are often supplemented with calcium channel blockers (CCBs) for treatment of hypertension. We recently showed that the L/N-type CCB cilnidipine has superior cardioprotective effects compared with the L-type CCB amlodipine in Dahl salt-sensitive (DS) rats. We have now compared the effects of the ARB valsartan combined with cilnidipine or amlodipine on cardiac pathophysiology in DS rats. DS rats fed a high-salt diet from 6 weeks of age were treated with vehicle, valsartan alone (10 mg kg(-1) per day), or valsartan combined with either cilnidipine (1 mg kg(-1) per day) or amlodipine (1 mg kg(-1) per day) from 7 to 11 weeks. The salt-induced increase in systolic blood pressure apparent in the vehicle group was attenuated similarly in the three drug treatment groups. Valsartan-cilnidipine attenuated left ventricular (LV) fibrosis and diastolic dysfunction as well as cardiac oxidative stress and inflammation to a greater extent than did valsartan alone or valsartan-amlodipine. In addition, the increases in urinary excretion of dopamine and epinephrine as well as in cardiac renin-angiotensin-aldosterone-system (RAAS) gene expression apparent in vehicle-treated rats were attenuated to a greater extent by valsartan-cilnidipine than by the other two treatments. Valsartan-cilnidipine thus attenuated LV remodeling and diastolic dysfunction more effectively than did valsartan or valsartan-amlodipine in rats with salt-sensitive hypertension, and this superior cardioprotective action of valsartan-cilnidipine compared with valsartan-amlodipine is likely attributable, at least in part, to the greater antioxidant and antiinflammatory effects associated with both greater inhibition of cardiac RAAS gene expression and N-type calcium channel blockade.

Increased salt intake during early ontogenesis lead to development of arterial hypertension in salt-resistant Wistar rats.

PubMed

Svitok, Pavel; Molcan, Lubos; Vesela, Anna; Kruzliak, Peter; Moravcik, Roman; Zeman, Michal

2015-01-01

A direct relationship exists between salt consumption and hypertension. Increased sodium intake does not automatically lead to a rise in blood pressure (BP) because of marked intra-individual variability in salt sensitivity. Wistar rats are a salt-resistant strain and increased salt intake in adults does not induce hypertension. Mechanisms regulating BP develop during early ontogenesis and increased sodium consumption by pregnant females leads to an increase in BP of their offspring, but early postnatal stages have not been sufficiently analyzed in salt-resistant strains of rats. The aim of this work was to study the effects of increased salt during early ontogeny on cardiovascular characteristics of Wistar rats. We used 16 control (C; 8 males + 8 females) rats fed with a standard diet (0.2% sodium) and 16 experimental (S; 8 males + 8 females) rats fed with a diet containing 0.8% sodium. BP was measured weekly and plasma renin activity, aldosterone and testosterone concentrations were assayed by radioimmunoassay after the experiment in 16-week-old animals. In the kidney, AT1 receptors were determined by the western blot. BP was higher in the S as compared with the C rats and did not differ between males and females. The relative left ventricle mass was increased in S as compared with C males and no differences were recorded in females. No significant differences between groups were found in hormonal parameters and AT1 receptors. Results indicate that moderately increased salt intake during postnatal ontogeny results in a BP rise even in salt-resistant rats.

Mitochondrial proteomic analysis reveals deficiencies in oxygen utilization in medullary thick ascending limb of Henle in the Dahl salt-sensitive rat

PubMed Central

Zheleznova, Nadezhda N.; Yang, Chun; Ryan, Robert P.; Halligan, Brian D.; Liang, Mingyu; Greene, Andrew S.

2012-01-01

The renal medullary thick ascending limb (mTAL) of the Dahl salt-sensitive (SS) rat is the site of enhanced NaCl reabsorption and excess superoxide production. In the present studies we isolated mitochondria from mTAL of SS and salt-resistant control strain SS.13BN rats on 0.4 and 8% salt diet for 7 days and performed a proteomic analysis. Purity of mTAL and mitochondria isolations exceeded 93.6 and 55%, respectively. Using LC/MS spectral analysis techniques we identified 96 mitochondrial proteins in four biological mTAL mitochondria samples, run in duplicate, as defined by proteins with a false discovery rate <5% and scan count ≥2. Seven of these 96 proteins, including IDH2, ACADM, SCOT, Hsp60, ATPA, EFTu, and VDAC2 were differentially expressed between the two rat strains. Oxygen consumption and high-resolution respirometry analyses showed that mTAL cells and the mitochondria in the outer medulla of SS rats fed high-salt diet exhibited lower rates of oxygen utilization compared with those from SS.13BN rats. These studies advance the conventional proteomic paradigm of focusing exclusively upon whole tissue homogenates to a focus upon a single cell type and specific subcellular organelle. The results reveal the importance of a largely unexplored role for deficiencies of mTAL mitochondrial metabolism and oxygen utilization in salt-induced hypertension and renal medullary oxidative stress. PMID:22805345

Preventive and therapeutic effect of brozopine on stroke in Dahl Salt-sensitive hypertensive rats.

PubMed

Gao, Yuan; Wang, Yan; Li, Miao; Liu, Yali; Chang, Junbiao; Qiao, Hailing

2017-10-01

Our aim was to explore the preventive and therapeutic effects of sodium (±)-5-bromo-2-(α-hydroxypentyl) benzoate (brand name: brozopine, BZP) on stroke in Dahl Salt-sensitive (Dahl-SS) hypertensive rats. Dahl-SS rats were fed a high-salt diet to observe the effect of BZP on blood pressure, and brain, heart, and kidney tissues. Additionally, the incidence of stroke was recorded according to the neurological score. The relative mechanisms investigated included anti-oxidative effects and anti-platelet aggregation. BZP reduced the incidence of stroke, neuronal necrosis in the brain, and cell swelling and inflammatory infiltration in the kidney. Its mechanisms were related to the increased activities of gluthatione peroxidase and catalase and the decreased level of plasma nitric oxide. BZP inhibited arachidonic acid (AA) - induced platelet aggregation (IC 50 : 12µM) rather than that of adenosine diphosphate (ADP) - and/or thrombin-induced platelet aggregation in vitro. Interestingly, BZP inhibited ADP-, thrombin-, or AA-induced platelet aggregation and elevated the level of AMP-activated protein kinase, cyclic guanosine monophosphate, and vasodilator-stimulated-phosphoprotein, and attenuated ATP contents and mitogen-activated protein kinase levels in platelet and inhibited thrombus formation in a carotid artery thrombosis model, dose-dependently, in Dahl-SS hypertensive-induced stroke rats. In conclusion, BZP can have therapeutic and preventive effects on stroke in Dahl-SS hypertensive rats, the mechanisms of which may be related to anti-oxidant, anti-platelet aggregation and anti-thrombus formation. Copyright © 2017 Elsevier B.V. All rights reserved.

Sex-specific genetic determinants for arterial stiffness in Dahl salt-sensitive hypertensive rats.

PubMed

Decano, Julius L; Pasion, Khristine A; Black, Nicole; Giordano, Nicholas J; Herrera, Victoria L; Ruiz-Opazo, Nelson

2016-01-11

Arterial stiffness is an independent predictor of cardiovascular outcomes in hypertensive patients including myocardial infarction, fatal stroke, cerebral micro-bleeds which predicts cerebral hemorrhage in hypertensive patients, as well as progression to hypertension in non-hypertensive subjects. The association between arterial stiffness and various cardiovascular outcomes (coronary heart disease, stroke) remains after adjusting for age, sex, blood pressure, body mass index and other known predictors of cardiovascular disease, suggesting that arterial stiffness, measured via carotid-femoral pulse wave velocity, has a better predictive value than each of these factors. Recent evidence shows that arterial stiffening precedes the onset of high blood pressure; however their molecular genetic relationship (s) and sex-specific determinants remain uncertain. We investigated whether distinct or shared genetic determinants might underlie susceptibility to arterial stiffening in male and female Dahl salt-sensitive rats. Thus, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting arterial stiffness in six-week old F2 (Dahl S x R)-intercross male and female rats characterized for abdominal aortic pulse wave velocity and aortic strain by high-resolution ultrasonography. We detected five highly significant QTLs affecting aortic stiffness: two interacting QTLs (AS-m1 on chromosome 4 and AS-m2 on chromosome16, LOD 8.8) in males and two distinct interacting QTLs (AS-f1 on chromosome 9 and AS-f2 on chromosome11, LOD 8.9) in females affecting pulse wave velocity. One QTL (AS-1 on chromosome 3, LOD 4.3) was found to influence aortic strain in a sex-independent manner. None of these arterial stiffness QTLs co-localized with previously reported blood pressure QTLs detected in equivalent genetic intercrosses. These data reveal sex-specific genetic determinants for aortic pulse wave velocity and suggest distinct polygenic susceptibility for arterial stiffness and

Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.

PubMed

Geurts, Aron M; Mattson, David L; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M; Kurth, Theresa M; Yang, Chun; Endres, Bradley T; Klotz, Jason; Liang, Mingyu; Cowley, Allen W

2015-02-01

Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. © 2014 American Heart Association, Inc.

Prenatal exposure to angiotensin II increases blood pressure and decreases salt sensitivity in rats.

PubMed

Svitok, Pavel; Senko, Tomas; Panakova, Zuzana; Olexova, Lucia; Krskova, Lucia; Okuliarova, Monika; Zeman, Michal

2017-01-01

Renin angiotensin aldosterone system (RAAS) plays an essential role in the homeostatic control of arterial blood pressure, perfusion of tissues, and control of extracellular fluid. Its components are highly expressed in the developing kidney, general vasculature, brain, and heart. A modified intrauterine environment alters mechanisms controlling blood pressure (BP) and can lead to hypertension in the adult offspring and developmentally programmed RAAS can be involved in this process. There are very little data about the effects of increased angiotensin II (Ang II) concentrations during pregnancy on in utero development of the fetus. In our study, we administered Ang II to pregnant female rats via osmotic mini-pumps and evaluated the postnatal development and BP control in the offspring. To estimate possible developmental changes in sensitivity to salt, we exposed the offspring to a diet with increased salt content and measured plasma aldosterone levels and plasma renin activity. Increased Ang II during pregnancy raised BP in the offspring; however, salt sensitivity was decreased in comparison to controls. Relative weight of the left ventricle was decreased in the offspring prenatally exposed to Ang II, while relative kidney weight was reduced only in female offspring. Prenatal treatment led to increased aldosterone levels and decreased plasma renin activity, suggesting a complex physiological response. Our results suggest that conditions leading to upregulation of RAAS during pregnancy can influence the cardiovascular system of the fetus and have a long-term impact on the offspring's health.

Effects of p67phox on the mitochondrial oxidative state in the kidney of Dahl salt-sensitive rats: optical fluorescence 3-D cryoimaging

PubMed Central

Salehpour, F.; Ghanian, Z.; Yang, C.; Zheleznova, N. N.; Kurth, T.; Dash, R. K.; Cowley, A. W.

2015-01-01

The goal of the present study was to quantify and correlate the contribution of the cytosolic p67phox subunit of NADPH oxidase 2 to mitochondrial oxidative stress in the kidneys of the Dahl salt-sensitive (SS) hypertensive rat. Whole kidney redox states were uniquely assessed using a custom-designed optical fluorescence three-dimensional cryoimager to acquire multichannel signals of the intrinsic fluorophores NADH and FAD. SS rats were compared with SS rats in which the cytosolic subunit p67phox was rendered functionally inactive by zinc finger nuclease mutation of the gene (SSp67phox-null rats). Kidneys of SS rats fed a 0.4% NaCl diet exhibited significantly (P = 0.023) lower tissue redox ratio (NADH/FAD; 1.42 ± 0.06, n = 5) than SSp67phox-null rats (1.64 ± 0.07, n = 5), indicating reduced levels of mitochondrial electron transport chain metabolic activity and enhanced oxidative stress in SS rats. When fed a 4.0% salt diet for 21 days, both strains exhibited significantly lower tissue redox ratios (P < 0.001; SS rats: 1.03 ± 0.05, n = 9, vs. SSp67phox-null rats: 1.46 ± 0.04, n = 7) than when fed a 0.4% salt, but the ratio was still significantly higher in SSp67phox rats at the same salt level as SS rats. These results are consistent with results from previous studies that found elevated medullary interstitial fluid concentrations of superoxide and H2O2 in the medulla of SS rats. We conclude that the p67phox subunit of NADPH oxidase 2 plays an important role in the excess production of ROS from mitochondria in the renal medulla of the SS rat. PMID:26062875

Effects of p67phox on the mitochondrial oxidative state in the kidney of Dahl salt-sensitive rats: optical fluorescence 3-D cryoimaging.

PubMed

Salehpour, F; Ghanian, Z; Yang, C; Zheleznova, N N; Kurth, T; Dash, R K; Cowley, A W; Ranji, M

2015-08-15

The goal of the present study was to quantify and correlate the contribution of the cytosolic p67(phox) subunit of NADPH oxidase 2 to mitochondrial oxidative stress in the kidneys of the Dahl salt-sensitive (SS) hypertensive rat. Whole kidney redox states were uniquely assessed using a custom-designed optical fluorescence three-dimensional cryoimager to acquire multichannel signals of the intrinsic fluorophores NADH and FAD. SS rats were compared with SS rats in which the cytosolic subunit p67(phox) was rendered functionally inactive by zinc finger nuclease mutation of the gene (SS(p67phox)-null rats). Kidneys of SS rats fed a 0.4% NaCl diet exhibited significantly (P = 0.023) lower tissue redox ratio (NADH/FAD; 1.42 ± 0.06, n = 5) than SS(p67phox)-null rats (1.64 ± 0.07, n = 5), indicating reduced levels of mitochondrial electron transport chain metabolic activity and enhanced oxidative stress in SS rats. When fed a 4.0% salt diet for 21 days, both strains exhibited significantly lower tissue redox ratios (P < 0.001; SS rats: 1.03 ± 0.05, n = 9, vs. SS(p67phox)-null rats: 1.46 ± 0.04, n = 7) than when fed a 0.4% salt, but the ratio was still significantly higher in SS(p67phox) rats at the same salt level as SS rats. These results are consistent with results from previous studies that found elevated medullary interstitial fluid concentrations of superoxide and H2O2 in the medulla of SS rats. We conclude that the p67(phox) subunit of NADPH oxidase 2 plays an important role in the excess production of ROS from mitochondria in the renal medulla of the SS rat. Copyright © 2015 the American Physiological Society.

A cockspur for the DSS cells: Erythrina crista-galli sensitizers

NASA Astrophysics Data System (ADS)

Enciso, Paula; Decoppet, Jean-David; Grätzel, Michael; Wörner, Michael; Cabrerizo, Franco M.; Cerdá, María Fernanda

2017-04-01

Dye sensitized solar cells were assembled employing a mixture of anthocyanins extracted from red ceibo's flowers. At the literature different extraction procedures are reported to extract anthocyanins from natural products and sensitize the cells. In order to compare them, different methods were followed to set the cells under the same conditions. Assembled cells showed very interesting conversion efficiency values, reaching a 0.73% value for extracts purified using C18 column, in open cells under illumination using a solar light simulator, 1 sun, 1.5 AM. Data reported herein prove that anthocyanins obtained from ceibo's flower, after simple further purification, might represent an excellent, cheap and clean alternative for the development of DSS cells.

Optical cryoimaging of rat kidney and the effective role of chromosome 13 in salt-induced hypertension

NASA Astrophysics Data System (ADS)

Salehpour, F.; Yang, C.; Kurth, T.; Cowley, A. W.; Ranji, M.

2015-03-01

The objective of this work is to assess oxidative stress levels in salt-sensitive hypertension animal model using 3D optical cryoimager to image mitochondrial redox ratio. We studied Dahl salt-induced (SS) rats, and compared the results with a consomic SS rat strain (SSBN13). The SSBN13 strain was developed by the introgression of chromosome from the Brown Norway (BN) rat into the salt-sensitive (SS) genetic background and exhibits significant protection from salt induced hypertension1 . These two groups were fed on a high salt diet of 8.0% NaCl for one week. Mitochondrial redox ratio (NADH/FAD=NADH RR), was used as a quantitative marker of the oxidative stress in kidney tissue. Maximum intensity projected images and their corresponding histograms in each group were acquired from each kidney group. The result showed a 49% decrease in mitochondrial redox ratio of SS compared to SSBN13 translated to an increase in the level of oxidative stress of the tissue. Therefore, the results quantify oxidative stress levels and its effect on mitochondrial redox in salt sensitive hypertension.

BTZO-15, an ARE-Activator, Ameliorates DSS- and TNBS-Induced Colitis in Rats

PubMed Central

Yukitake, Hiroshi; Kimura, Haruhide; Suzuki, Hirobumi; Tajima, Yasukazu; Sato, Yoshimi; Imaeda, Toshihiro; Kajino, Masahiro; Takizawa, Masayuki

2011-01-01

Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that are primarily represented by ulcerative colitis and Crohn's disease. The etiology of IBD is not well understood; however, oxidative stress is considered a potential etiological and/or triggering factor for IBD. We have recently reported the identification of BTZO-1, an activator of antioxidant response element (ARE)-mediated gene expression, which protects cardiomyocytes from oxidative stress-induced insults. Here we describe the potential of BTZO-15, an active BTZO-1 derivative for ARE-activation with a favorable ADME-Tox profile, for the treatment of IBD. BTZO-15 induced expression of heme oxygenase-1 (HO-1), an ARE-regulated cytoprotective protein, and inhibited NO-induced cell death in IEC-18 cells. Large intestine shortening, rectum weight gain, diarrhea, intestinal bleeding, and an increase in rectal myeloperoxidase (MPO) activity were observed in a dextran sulfate sodium (DSS)-induced colitis rat model. Oral administration of BTZO-15 induced HO-1 expression in the rectum and attenuated DSS-induced changes. Furthermore BTZO-15 reduced the ulcerated area and rectal MPO activity in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rats without affecting rectal TNF-α levels. These results suggest that BTZO-15 is a promising compound for a novel IBD therapeutic drug with ARE activation properties. PMID:21853095

Dietary salt restriction improves cardiac and adipose tissue pathology independently of obesity in a rat model of metabolic syndrome.

PubMed

Hattori, Takuya; Murase, Tamayo; Takatsu, Miwa; Nagasawa, Kai; Matsuura, Natsumi; Watanabe, Shogo; Murohara, Toyoaki; Nagata, Kohzo

2014-12-02

Metabolic syndrome (MetS) enhances salt sensitivity of blood pressure and is an important risk factor for cardiovascular disease. The effects of dietary salt restriction on cardiac pathology associated with metabolic syndrome remain unclear. We investigated whether dietary salt restriction might ameliorate cardiac injury in DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, which are derived from a cross between Dahl salt-sensitive and Zucker rats and represent a model of metabolic syndrome. DS/obese rats were fed a normal-salt (0.36% NaCl in chow) or low-salt (0.0466% NaCl in chow) diet from 9 weeks of age and were compared with similarly treated homozygous lean littermates (DahlS.Z-Lepr(+)/Lepr(+), or DS/lean rats). DS/obese rats fed the normal-salt diet progressively developed hypertension and showed left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 15 weeks. Dietary salt restriction attenuated all of these changes in DS/obese rats. The levels of cardiac oxidative stress and inflammation and the expression of cardiac renin-angiotensin-aldosterone system genes were increased in DS/obese rats fed the normal-salt diet, and dietary salt restriction downregulated these parameters in both DS/obese and DS/lean rats. In addition, dietary salt restriction attenuated the increase in visceral adipose tissue inflammation and the decrease in insulin signaling apparent in DS/obese rats without reducing body weight or visceral adipocyte size. Dietary salt restriction did not alter fasting serum glucose levels but it markedly decreased the fasting serum insulin concentration in DS/obese rats. Dietary salt restriction not only prevents hypertension and cardiac injury but also ameliorates insulin resistance, without reducing obesity, in this model of metabolic syndrome. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Induction of colitis in young rats by dextran sulfate sodium.

PubMed

Vicario, María; Crespí, Mar; Franch, Angels; Amat, Concepció; Pelegrí, Carme; Moretó, Miquel

2005-01-01

Models using dextran sulfate sodium (DSS) to induce experimental colitis in rodents have been performed mostly in adult animals. For this reason, we aimed to develop a model of colitis in young rats. DSS was administered to 30-day-old rats at concentrations ranging from 0.5 to 5% in drinking water. Young rats were remarkably sensitive to DSS since clinical symptoms rapidly rose with 5% DSS and most animals died after the fifth day. With 1 and 2% DSS, the severity of mucosal lesions was also high on day 7, the animals showing leukocytosis and anemia. At 0.5% DSS, leukocytosis and mild colonic lesions were induced. This concentration of DSS significantly increased myeloperoxidase activity and goblet cell number in the colon, indicating mucosal inflammation. Since food consumption was not reduced by 0.5% DSS, we suggest that this protocol can be used to study the effects of dietary supplements on intestinal inflammatory processes.

Induction of Colitis in Young Rats by Dextran Sulfate Sodium.

PubMed

Vicario, María; Crespí, Mar; Franch, Àngels; Amat, Concepció; Pelegrí, Carme; Moretó, Miquel

2005-01-01

Models using dextran sulfate sodium (DSS) to induce experimental colitis in rodents have been performed mostly in adult animals. For this reason, we aimed to develop a model of colitis in young rats. DSS was administered to 30-day-old rats at concentrations ranging from 0.5 to 5% in drinking water. Young rats were remarkably sensitive to DSS since clinical symptoms rapidly rose with 5% DSS and most animals died after the fifth day. With 1 and 2% DSS, the severity of mucosal lesions was also high on day 7, the animals showing leukocytosis and anemia. At 0.5% DSS, leukocytosis and mild colonic lesions were induced. This concentration of DSS significantly increased myeloperoxidase activity and goblet cell number in the colon, indicating mucosal inflammation. Since food consumption was not reduced by 0.5% DSS, we suggest that this protocol can be used to study the effects of dietary supplements on intestinal inflammatory processes.

Glucose-independent renoprotective mechanisms of the tissue dipeptidyl peptidase-4 inhibitor, saxagliptin, in Dahl salt-sensitive hypertensive rats.

PubMed

Uchii, Masako; Kimoto, Naoya; Sakai, Mariko; Kitayama, Tetsuya; Kunori, Shunji

2016-07-15

Although previous studies have shown an important role of renal dipeptidyl peptidase-4 (DPP-4) inhibition in ameliorating kidney injury in hypertensive rats, the renal distribution of DPP-4 and mechanisms of renoprotective action of DPP-4 inhibition remain unclear. In this study, we examined the effects of the DPP-4 inhibitor saxagliptin on DPP-4 activity in renal cells (using in situ DPP-4 staining) and on renal gene expression related to inflammation and fibrosis in the renal injury in hypertensive Dahl salt-sensitive (Dahl-S) rats. Male rats fed a high-salt (8% NaCl) diet received vehicle (water) or saxagliptin (12.7mg/kg/day) for 4 weeks. Blood pressure (BP), serum glucose and 24-h urinary albumin and sodium excretions were measured, and renal histopathology was performed. High salt-diet increased BP and urinary albumin excretion, consequently resulting in glomerular sclerosis and tubulointerstitial fibrosis. Although saxagliptin did not affect BP and blood glucose levels, it significantly ameliorated urinary albumin excretion. In situ staining showed DPP-4 activity in glomerular and tubular cells. Saxagliptin significantly suppressed DPP-4 activity in renal tissue extracts and in glomerular and tubular cells. Saxagliptin also significantly attenuated the increase in inflammation and fibrosis-related gene expressions in the kidney. Our results demonstrate that saxagliptin inhibited the development of renal injury independent of its glucose-lowering effect. Glomerular and tubular DPP-4 inhibition by saxagliptin was associated with improvements in albuminuria and the suppression of inflammation and fibrosis-related genes. Thus, local glomerular and tubular DPP-4 inhibition by saxagliptin may play an important role in its renoprotective effects in Dahl-S rats. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Chronic Inhibition of Renal Outer Medullary Potassium Channel Not Only Prevented but Also Reversed Development of Hypertension and End-Organ Damage in Dahl Salt-Sensitive Rats.

PubMed

Zhou, Xiaoyan; Forrest, Michael J; Sharif-Rodriguez, Wanda; Forrest, Gail; Szeto, Daphne; Urosevic-Price, Olga; Zhu, Yonghua; Stevenson, Andra S; Zhou, Yuchen; Stribling, Sloan; Dajee, Maya; Walsh, Shawn P; Pasternak, Alexander; Sullivan, Kathleen A

2017-02-01

The renal outer medullary potassium (ROMK) channel mediates potassium recycling and facilitates sodium reabsorption through the Na + /K + /2Cl - cotransporter in the loop of Henle and potassium secretion at the cortical collecting duct. Evidence from the phenotype of humans and rodents with functional ROMK deficiency supports the contention that selective ROMK inhibitors (ROMKi) will represent a novel diuretic with potential of therapeutic benefit for hypertension. ROMKi have recently been synthesized by Merck & Co, Inc. The present studies were designed to examine the effects of ROMKi B on systemic hemodynamics, renal function and structure, and vascular function in Dahl salt-sensitive rats. Four experimental groups-control, high-salt diet alone; ROMKi B 3 mg·kg - 1 ·d - 1 ; ROMKi B 10 mg·kg - 1 ·d - 1 ; and hydrochlorothiazide 25 mg·kg - 1 ·d - 1 -were included in prophylactic (from week 1 to week 9 on high-salt diet) and therapeutic studies (from week 5 to week 9 on high-salt diet), respectively. ROMKi B produced sustained blood pressure reduction and improved renal and vascular function and histological alterations induced by a high-salt diet. ROMKi B was superior to hydrochlorothiazide at reducing blood pressure. Furthermore, ROMKi B provided beneficial effects on both the plasma lipid profile and bone mineral density. Chronic ROMK inhibition not only prevented but also reversed the development of hypertension and end-organ damage in Dahl salt-sensitive rats. Our findings suggest a potential utility of ROMKi B as a novel antihypertensive agent, particularly for the treatment of the salt-sensitive hypertension patient population. © 2016 American Heart Association, Inc.

Critical role of renal dipeptidyl peptidase-4 in ameliorating kidney injury induced by saxagliptin in Dahl salt-sensitive hypertensive rats.

PubMed

Sakai, Mariko; Uchii, Masako; Myojo, Kensuke; Kitayama, Tetsuya; Kunori, Shunji

2015-08-15

Saxagliptin, a potent dipeptidyl peptidase-4 (DPP-4) inhibitor, is currently used to treat type 2 diabetes mellitus, and it has been reported to exhibit a slower rate of dissociation from DPP-4 compared with another DPP-4 inhibitor, sitagliptin. In this study, we compared the effects of saxagliptin and sitagliptin on hypertension-related renal injury and the plasma and renal DPP-4 activity levels in Dahl salt-sensitive hypertensive (Dahl-S) rats. The high-salt diet (8% NaCl) significantly increased the blood pressure and quantity of urinary albumin excretion and induced renal glomerular injury in the Dahl-S rats. Treatment with saxagliptin (14mg/kg/day via drinking water) for 4 weeks significantly suppressed the increase in urinary albumin excretion and tended to ameliorate glomerular injury without altering the blood glucose levels and systolic blood pressure. On the other hand, the administration of sitagliptin (140mg/kg/day via drinking water) did not affect urinary albumin excretion and glomerular injury in the Dahl-S rats. Meanwhile, the high-salt diet increased the renal DPP-4 activity but did not affect the plasma DPP-4 activity in the Dahl-S rats. Both saxagliptin and sitagliptin suppressed the plasma DPP-4 activity by 95% or more. Although the renal DPP-4 activity was also inhibited by both drugs, the inhibitory effect of saxagliptin was more potent than that of sitagliptin. These results indicate that saxagliptin has a potent renoprotective effect in the Dahl-S rats, independent of its glucose-lowering actions. The inhibition of the renal DPP-4 activity induced by saxagliptin may contribute to ameliorating renal injury in hypertension-related renal injury. Copyright © 2015 Elsevier B.V. All rights reserved.

Pathophysiology of salt sensitivity hypertension.

PubMed

Ando, Katsuyuki; Fujita, Toshiro

2012-06-01

Dietary salt intake is the most important factor contributing to hypertension, but the salt susceptibility of blood pressure (BP) is different in individual subjects. Although the pathogenesis of salt-sensitive hypertension is heterogeneous, it is mainly attributable to an impaired renal capacity to excrete sodium (Na(+) ). We recently identified two novel mechanisms that impair renal Na(+) -excreting function and result in an increase in BP. First, mineralocorticoid receptor (MR) activation in the kidney, which facilitates distal Na(+) reabsorption through epithelial Na(+) channel activation, causes salt-sensitive hypertension. This mechanism exists not only in models of high-aldosterone hypertension as seen in conditions of obesity or metabolic syndrome, but also in normal- or low-aldosterone type of salt-sensitive hypertension. In the latter, Rac1 activation by salt excess causes MR stimulation. Second, renospecific sympathoactivation may cause an increase in BP under conditions of salt excess. Renal beta2 adrenoceptor stimulation in the kidney leads to decreased transcription of the gene encoding WNK4, a negative regulator of Na(+) reabsorption through Na(+) -Cl (-) cotransporter in the distal convoluted tubules, resulting in salt-dependent hypertension. Abnormalities identified in these two pathways of Na(+) reabsorption in the distal nephron may present therapeutic targets for the treatment of salt-sensitive hypertension.

Intake of water with high levels of dissolved hydrogen (H2) suppresses ischemia-induced cardio-renal injury in Dahl salt-sensitive rats.

PubMed

Zhu, Wan-Jun; Nakayama, Masaaki; Mori, Takefumi; Nakayama, Keisuke; Katoh, Junichiro; Murata, Yaeko; Sato, Toshinobu; Kabayama, Shigeru; Ito, Sadayoshi

2011-07-01

Hydrogen (H(2)) reportedly produces an antioxidative effect by quenching cytotoxic oxygen radicals. We studied the biological effects of water with dissolved H(2) on ischemia-induced cardio-renal injury in a rat model of chronic kidney disease (CKD). Dahl salt-sensitive rats (7 weeks old) were allowed ad libitum drinking of filtered water (FW: dissolved H(2), 0.00 ± 0.00 mg/L) or water with dissolved H(2) produced by electrolysis (EW: dissolved H(2), 0.35 ± 0.03 mg/L) for up to 6 weeks on a 0.5% salt diet. The rats then underwent ischemic reperfusion (I/R) of one kidney and were killed a week later for investigation of the contralateral kidney and the heart. In the rats given FW, unilateral kidney I/R induced significant increases in plasma monocyte chemoattractant protein-1, methylglyoxal and blood urea nitrogen. Histologically, significant increases were found in glomerular adhesion, cardiac fibrosis, number of ED-1 (CD68)-positive cells and nitrotyrosine staining in the contralateral kidney and the heart. In rats given EW, those findings were significantly ameliorated and there were significant histological differences between rats given FW and those given EW. Consumption of EW by ad libitum drinking has the potential to ameliorate ischemia-induced cardio-renal injury in CKD model rats. This indicates a novel strategy of applying H(2) produced by water electrolysis technology for the prevention of CKD cardio-renal syndrome.

Hydrogen gas improves left ventricular hypertrophy in Dahl rat of salt-sensitive hypertension.

PubMed

Matsuoka, Hiroki; Miyata, Seiko; Okumura, Nozomi; Watanabe, Takuya; Hashimoto, Katsunori; Nagahara, Miki; Kato, Kazuko; Sobue, Sayaka; Takeda, Kozue; Ichihara, Masatoshi; Iwamoto, Takashi; Noda, Akiko

2018-06-14

Hypertension is an important risk factor for death resulting from stroke, myocardial infarction, and end-stage renal failure. Hydrogen (H 2 ) gas protects against many diseases, including ischemia-reperfusion injury and stroke. The effects of H 2 on hypertension and its related left ventricular (LV) function have not been fully elucidated. The purpose of this study was to investigate the effects of H 2 gas on hypertension and LV hypertrophy using echocardiography. Dahl salt-sensitive (DS) rats were randomly divided into three groups: those fed an 8% NaCl diet until 12 weeks of age (8% NaCl group), those additionally treated with H 2 gas (8% NaCl + H 2 group), and control rats maintained on a diet containing 0.3% NaCl until 12 weeks of age (0.3% NaCl group). H 2 gas was supplied through a gas flowmeter and delivered by room air (2% hydrogenated room air, flow rate of 10 L/min) into a cage surrounded by an acrylic chamber. We evaluated interventricular septal wall thickness (IVST), LV posterior wall thickness (LVPWT), and LV mass using echocardiography. IVST, LVPWT, and LV mass were significantly higher in the 8% NaCl group than the 0.3% NaCl group at 12 weeks of age, whereas they were significantly lower in the 8% NaCl + H 2 group than the 8% NaCl group. There was no significant difference in systolic blood pressure between the two groups. Our findings suggest that chronic H 2 gas inhalation may help prevent LV hypertrophy in hypertensive DS rats.

Blood pressure, magnesium and other mineral balance in two rat models of salt-sensitive, induced hypertension: effects of a non-peptide angiotensin II receptor type 1 antagonist.

PubMed

Rondón, Lusliany Josefina; Marcano, Eunice; Rodríguez, Fátima; del Castillo, Jesús Rafael

2014-01-01

The renin-angiotensin system is critically involved in regulating arterial blood pressure (BP). Inappropriate angiotensin type-1 receptor activation by angiotensin-II (Ang-II) is related to increased arterial BP. Mg has a role in BP; it can affect cardiac electrical activity, myocardial contractility, and vascular tone. To evaluate the relationship between high BP induced by a high sodium (Na) diet and Mg, and other mineral balances, two experimental rat models of salt-sensitive, induced-hypertension were used: Ang-II infused and Dahl salt-sensitive (SS) rats. We found that: 1) Ang-II infusion progressively increased BP, which was accompanied by hypomagnesuria and signs of secondary hyperaldosteronism; 2) an additive effect between Ang-II and a high Na load may have an effect on strontium (Sr), zinc (Zn) and copper (Cu) balances; 3) Dahl SS rats fed a high Na diet had a slow pressor response, accompanied by altered Mg, Na, potassium (K), and phosphate (P) balances; and 4) losartan prevented BP increases induced by Ang II-NaCl, but did not modify mineral balances. In Dahl SS rats, losartan attenuated high BP and ameliorated magnesemia, Na and K balances. Mg metabolism maybe considered a possible defect in this strain of rat that may contribute to hypertension.

Lactobacillus reuteri Maintains a Functional Mucosal Barrier during DSS Treatment Despite Mucus Layer Dysfunction

PubMed Central

Willing, Ben; Petersson, Joel; Rang, Sara; Phillipson, Mia; Holm, Lena; Roos, Stefan

2012-01-01

Treatment with the probiotic bacterium Lactobacillus reuteri has been shown to prevent dextran sodium sulfate (DSS)-induced colitis in rats. This is partly due to reduced P-selectin-dependent leukocyte- and platelet-endothelial cell interactions, however, the mechanism behind this protective effect is still unknown. In the present study a combination of culture dependent and molecular based T-RFLP profiling was used to investigate the influence of L. reuteri on the colonic mucosal barrier of DSS treated rats. It was first demonstrated that the two colonic mucus layers of control animals had different bacterial community composition and that fewer bacteria resided in the firmly adherent layer. During DSS induced colitis, the number of bacteria in the inner firmly adherent mucus layer increased and bacterial composition of the two layers no longer differed. In addition, induction of colitis dramatically altered the microbial composition in both firmly and loosely adherent mucus layers. Despite protecting against colitis, treatment with L. reuteri did not improve the integrity of the mucus layer or prevent distortion of the mucus microbiota caused by DSS. However, L. reuteri decreased the bacterial translocation from the intestine to mesenteric lymph nodes during DSS treatment, which might be an important part of the mechanisms by which L. reuteri ameliorates DSS induced colitis. PMID:23029509

Sustained ELABELA Gene Therapy in High-salt Diet-induced Hypertensive Rats.

PubMed

Schreiber, Claire A; Holditch, Sara J; Generous, Alex; Ikeda, Yasuhiro

2017-01-01

Elabela (ELA) is a recently identified apelin receptor agonist essential for cardiac development, but its biology and therapeutic potential are unclear. In humans, ELA transcripts are detected in embryonic stem cells, induced pluripotent stem cells, kidney, heart and blood vessels. ELA through the apelin (APJ) receptor promotes angiogenesis in vitro, relaxes murine aortic blood vessels and attenuates high blood pressure in vivo. The APJ receptor when bound to its original ligand, apelin, exerts peripheral vasodilatory and positive inotropic effects, conferring cardioprotection in vivo. This study initially assessed endogenous ELA expression in normal and diseased rats and then characterized the effects of long-term ELA gene delivery by adeno-associated virus serotype 9 (AAV9) vectors on cardiorenal function in Dahl salt-sensitive rats (DS) on a high-salt diet over 3 months. Endogenous ELA was predominantly expressed in the kidneys, especially in the renal collecting duct cells and was not affected by disease. Rat ELA was overexpressed in the heart via AAV9 vector by a single intravenous injection. ELA-treated animals showed delayed onset of blood pressure elevation. Prior to high-salt diet, a reduction in the fractional sodium and chloride excretion was observed in rats given the AAV9-ELA vector. After three months on a high-salt diet, ELA preserved glomerular architecture, decreased renal fibrosis and suppressed expression of fibrosis-associated genes in the kidneys. ELA is constitutively expressed in renal collecting ducts in rats. Sustained AAV-ELA expression may offer a potential long-term therapy for hypertension and renal remodeling. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Differential genetic basis for pre-menopausal and post-menopausal salt-sensitive hypertension.

PubMed

Herrera, Victoria L M; Pasion, Khristine A; Moran, Ann Marie; Ruiz-Opazo, Nelson

2012-01-01

Essential hypertension affects 75% of post-menopausal women in the United States causing greater cardiovascular complications compared with age-matched men and pre-menopausal women. Hormone replacement and current anti-hypertensive therapies do not correct this post-menopausal increased risk suggesting a distinct pathogenic framework. We investigated the hypothesis that distinct genetic determinants might underlie susceptibility to salt sensitive hypertension in pre-menopausal and post-menopausal states. To determine whether distinct genetic loci contribute to post-menopausal salt-sensitive hypertension, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting blood pressure (BP) in 16-month old post-menopausal F2 (Dahl S×R)-intercross female rats characterized for blood pressure by radiotelemetry. Given identical environments and high salt challenge, post-menopausal BP levels were significantly higher than observed in pre-menopausal (post-menopausal versus pre-menopausal SBP, P<0.0001) and ovariectomized (post-menopausal versus ovariectomized SBP, P<0.001) F2-intercross female rats. We detected four significant to highly significant BP-QTLs (BP-pm1 on chromosome 13, LOD 3.78; BP-pm2 on chromosome 11, LOD 2.76; BP-pm3 on chromosome 2, LOD 2.61; BP-pm4 on chromosome 4, LOD 2.50) and two suggestive BP-QTLs (BP-pm5 on chromosome 15, LOD 2.37; BP-f1 on chromosome 5, LOD 1.65), four of which (BP-pm2, BP-pm3, BP-pm4, BP-pm5) were unique to this post-menopausal cohort. These data demonstrate distinct polygenic susceptibility underlying post-menopausal salt-sensitive hypertension providing a pathway towards the identification of mechanism-based therapy for post-menopausal hypertension and ensuing target-organ complications.

Salt-Sensitive Hypertension: Perspectives on Intrarenal Mechanisms

PubMed Central

Majid, Dewan S.A.; Prieto, Minolfa C.; Navar, L Gabriel

2015-01-01

Salt sensitive hypertension is characterized by increases in blood pressure in response to increases in dietary salt intake and is associated with an enhanced risk of cardiovascular and renal morbidity. Although researchers have sought for decades to understand how salt sensitivity develops in humans, the mechanisms responsible for the increases in blood pressure in response to high salt intake are complex and only partially understood. Until now, scientists have been unable to explain why some individuals are salt sensitive and others are salt resistant. Although a central role for the kidneys in the development of salt sensitivity and hypertension has been generally accepted, it is also recognized that hypertension is of multifactorial origin and a variety of factors can induce, or prevent, blood pressure responsiveness to the manipulation of salt intake. Excess salt intake in susceptible persons may also induce inappropriate central and sympathetic nervous system responses and increase the production of intrarenal angiotensin II, catecholamines and other factors such as oxidative stress and inflammatory cytokines. One key factor is the concomitant inappropriate or paradoxical activation of the intrarenal renin-angiotensin system, by high salt intake. This is reflected by the increases in urinary angiotensinogen during high salt intake in salt sensitive models. A complex interaction between neuroendocrine factors and the kidney may underlie the propensity for some individuals to retain salt and develop salt-dependent hypertension. In this review, we focus mainly on the renal contributions that provide the mechanistic link between chronic salt intake and the development of hypertension. PMID:26028244

Low-Salt Intake during Mating or Gestation in Rats Is Associated with Low Birth and Survival Rates of Babies.

PubMed

Chou, Ranna; Hara, Anna; Du, DongDong; Shimizu, Namiko; Sakuyama, Hiroe; Uehara, Yoshio

2014-01-01

We investigated the influence of maternal salt restriction during mating or gestation on birth rate and offspring growth in Dahl salt-sensitive rats (DS). DS were divided into 5 groups: DS fed a low-salt (0.3% NaCl, w/w) (DS-low) or high-salt (4% NaCl, w/w) diet (DS-high) during mating and DS-high or DS-low during gestation, and DS fed regular chow (0.75% NaCl, w/w) (DS-regular) throughout mating and gestation. During the unspecified periods, the rats were given regular chow. DS-low during mating delivered fewer infants than high-salt mothers (P < 0.05). The birth rate on regular chow was 87%. Six out of 11 DS-low rats during pregnancy produced pups while the rats fed a high-salt diet all delivered pups (P < 0.025). The pup survival rate was 67% for high-salt mothers during mating and 54% for mothers on a low-salt diet. The pup survival rate was 95% for mothers on a high-salt diet during pregnancy and 64% for mothers on a low-salt diet (P < 0.0001). Seven out of 8 DS-regular rats during mating delivered 59 neonates. However, 66% of the neonates survived. A low-salt diet during mating or pregnancy lowers birth rate and the neonates from low-salt mothers during pregnancy were more likely to die than those from high-salt mothers.

Antihypertensive and anti-inflammatory actions of combined azilsartan and chlorthalidone in Dahl salt-sensitive rats on a high-fat, high-salt diet.

PubMed

Jin, Chunhua; O'Boyle, Sean; Kleven, Daniel T; Pollock, Jennifer S; Pollock, David M; White, John J

2014-08-01

Metabolic syndrome (MetS) and chronic kidney disease are global health issues. Metabolic syndrome induces hypertension and commonly results in renal damage. The optimal therapy for hypertension in MetS is unknown. Thiazide diuretics are first-line therapy; however, these drugs may have untoward effects. In the present study we investigated the effects of azilsartan (AZL), chlorthalidone (CLTD) and their combination on blood pressure and renal injury in a rodent model with features of MetS. Dahl salt-sensitive rats were fed high-fat (36% fat), high-salt (4% NaCl) diet. Groups were then treated with vehicle, AZL (3 mg/kg per day), CLTD (5 mg/kg per day) or AZL + CLTD. Mean arterial pressure was recorded continuously by telemetry. After 26 days, rats were killed humanely and their kidneys were harvested for histology. Both AZL and CLTD attenuated the rise in blood pressure compared with vehicle and the combination further reduced blood pressure compared with CLTD alone. All treatments reduced proteinuria and albuminuria. Nephrinuria was prevented only in groups treated with AZL. Nephrinuria was 57% lower and proteinuria was 47% lower with combination therapy compared with AZL alone. All treatments reduced the number of inflammatory cells in the kidney. In conclusion, in our model, AZL and CLTD lower blood pressure and exhibit renal protective effects. Treatment with AZL offers additional protection, as evidenced by lower nephrinuria and plasma monocyte chemoattractant protein-1 levels. Combination therapy afforded the greatest protective effects and may be the best choice for hypertensive therapy in MetS. © 2014 Wiley Publishing Asia Pty Ltd.

CNS neuroplasticity and salt-sensitive hypertension induced by prior treatment with subpressor doses of ANG II or aldosterone.

PubMed

Clayton, Sarah C; Zhang, Zhongming; Beltz, Terry; Xue, Baojian; Johnson, Alan Kim

2014-06-15

Although sensitivity to high dietary NaCl is regarded to be a risk factor for cardiovascular disease, the causes of salt-sensitive hypertension remain elusive. Previously, we have shown that rats pretreated with subpressor doses of either ANG II or aldosterone (Aldo) show sensitized hypertensive responses to a mild pressor dose of ANG II when tested after an intervening delay. The current studies investigated whether such treatments will induce salt sensitivity. In studies employing an induction-delay-expression experimental design, male rats were instrumented for chronic mean arterial pressure (MAP) recording. In separate experiments, ANG II, Aldo, or vehicle was delivered either subcutaneously or intracerebroventricularly during the induction. There were no sustained differences in BP during the delay prior to being given 2% saline. While consuming 2% saline during the expression, both ANG II- and Aldo-pretreated rats showed significantly greater hypertension. When hexamethonium was used to assess autonomic control of MAP, no differences in the decrease of MAP in response to ganglionic blockade were detected during the induction. However, during the expression, the fall was greater in sensitized rats. In separate experiments, brain tissue that was collected at the end of delay showed increases in message or activation of putative markers of neuroplasticity (i.e., brain-derived neurotrophic factor, p38 mitogen-activated protein kinase, and cAMP response element-binding protein). These experiments demonstrate that prior administration of nonpressor doses of either ANG II or Aldo will induce salt sensitivity. Collectively, our findings indicate that treatment with subpressor doses of ANG II and Aldo initiate central neuroplastic changes that are involved in hypertension of different etiologies. Copyright © 2014 the American Physiological Society.

Context-driven Salt Seeking Test (Rats)

PubMed Central

Chang, Stephen E.; Smith, Kyle S.

2018-01-01

Changes in reward seeking behavior often occur through incremental learning based on the difference between what is expected and what actually happens. Behavioral flexibility of this sort requires experience with rewards as better or worse than expected. However, there are some instances in which behavior can change through non-incremental learning, which requires no further experience with an outcome. Such an example of non-incremental learning is the salt appetite phenomenon. In this case, animals such as rats will immediately seek out a highly-concentrated salt solution that was previously undesired when they are put in a novel state of sodium deprivation. Importantly, this adaptive salt-seeking behavior occurs despite the fact that the rats never tasted salt in the depleted state, and therefore never tasted it as a highly desirable reward. The following protocol is a method to investigate the neural circuitry mediating adaptive salt seeking using a conditioned place preference (CPP) procedure. The procedure is designed to provide an opportunity to discover possible dissociations between the neural circuitry mediating salt seeking and salt consumption to replenish the bodily deficit after sodium depletion. Additionally, this procedure is amenable to incorporating a number of neurobiological techniques for studying the brain basis of this behavior.

Differential Genetic Basis for Pre-Menopausal and Post-Menopausal Salt-Sensitive Hypertension

PubMed Central

Herrera, Victoria L. M.; Pasion, Khristine A.; Moran, Ann Marie; Ruiz-Opazo, Nelson

2012-01-01

Essential hypertension affects 75% of post-menopausal women in the United States causing greater cardiovascular complications compared with age-matched men and pre-menopausal women. Hormone replacement and current anti-hypertensive therapies do not correct this post-menopausal increased risk suggesting a distinct pathogenic framework. We investigated the hypothesis that distinct genetic determinants might underlie susceptibility to salt sensitive hypertension in pre-menopausal and post-menopausal states. To determine whether distinct genetic loci contribute to post-menopausal salt-sensitive hypertension, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting blood pressure (BP) in 16-month old post-menopausal F2 (Dahl S×R)-intercross female rats characterized for blood pressure by radiotelemetry. Given identical environments and high salt challenge, post-menopausal BP levels were significantly higher than observed in pre-menopausal (post-menopausal versus pre-menopausal SBP, P<0.0001) and ovariectomized (post-menopausal versus ovariectomized SBP, P<0.001) F2-intercross female rats. We detected four significant to highly significant BP-QTLs (BP-pm1 on chromosome 13, LOD 3.78; BP-pm2 on chromosome 11, LOD 2.76; BP-pm3 on chromosome 2, LOD 2.61; BP-pm4 on chromosome 4, LOD 2.50) and two suggestive BP-QTLs (BP-pm5 on chromosome 15, LOD 2.37; BP-f1 on chromosome 5, LOD 1.65), four of which (BP-pm2, BP-pm3, BP-pm4, BP-pm5) were unique to this post-menopausal cohort. These data demonstrate distinct polygenic susceptibility underlying post-menopausal salt-sensitive hypertension providing a pathway towards the identification of mechanism-based therapy for post-menopausal hypertension and ensuing target-organ complications. PMID:22912817

Skeletal muscle insulin resistance in salt-sensitive hypertension: role of angiotensin II activation of NFκB.

PubMed

Zhou, Ming-Sheng; Liu, Chang; Tian, Runxia; Nishiyama, Akira; Raij, Leopoldo

2015-05-01

We have previously shown that in hypertensive Dahl salt-sensitive (DS) rats, impaired endothelium-dependent relaxation to acetylcholine and to insulin is mechanistically linked to up-regulation of angiotensin (Ang) II actions and the production of reactive oxygen species (ROS) and to activation of the proinflammatory transcription factor (NF)κB. Here we investigated whether Ang II activation of NFκB contributed to insulin resistance in the skeletal muscle of this animal model. DS rats were fed either a normal (NS, 0.5% NaCl) or high (HS, 4% NaCl) salt diet for 6 weeks. In addition, 3 separate groups of HS rats were given angiotensin receptor 1 blocker candesartan (ARB, 10 mg/kg/day in drinking water), antioxidant tempol (1 mmol/L in drinking water) or NFκB inhibitor PDTC (150 mg/kg in drinking water). DS rats manifested an increase in soleus muscle Ang II content, ROS production and phosopho-IκBα/IκBα ratio, ARB or tempol reduced ROS and phospho-IκBα/IκBα ratio. Hypertensive DS rats also manifested a reduction in glucose infusion rate, impaired insulin-induced Akt phosphorylation and Glut-4 translocation in the soleus muscle, which were prevented with treatment of either ARB, tempol, or PDTC. Data from the rat diabetes signaling pathway PCR array showed that 8 genes among 84 target genes were altered in the muscle of hypertensive rats with the increase in gene expression of ACE1 and 5 proinflammatory genes, and decrease of 2 glucose metabolic genes. Incubation of the muscle with NFκB SN50 (a specific peptide inhibitor of NFκB) ex vivo reversed changes in hypertension-induced gene expression. The current findings strongly suggest that the activation of NFκB inflammatory pathway by Ang II play a critical role in skeletal muscle insulin resistance in salt-sensitive hypertension.

Effects of Clofibrate on Salt Loading-Induced Hypertension in Rats

PubMed Central

Cruz, Antonio; Rodríguez-Gómez, Isabel; Pérez-Abud, Rocío; Vargas, Miguel Ángel; Wangensteen, Rosemary; Quesada, Andrés; Osuna, Antonio; Moreno, Juan Manuel

2011-01-01

The effects of clofibrate on the hemodynamic and renal manifestations of increased saline intake were analyzed. Four groups of male Wistar rats were treated for five weeks: control, clofibrate (240 mg/kg/day), salt (2% via drinking water), and salt + clofibrate. Body weight, systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, SBP, HR, and morphologic, metabolic, plasma, and renal variables were measured. Salt increased SBP, HR, urinary isoprostanes, NOx, ET, vasopressin and proteinuria and reduced plasma free T4 (FT4) and tissue FT4 and FT3 versus control rats. Clofibrate prevented the increase in SBP produced by salt administration, reduced the sodium balance, and further reduced plasma and tissue thyroid hormone levels. However, clofibrate did not modify the relative cardiac mass, NOx, urinary ET, and vasopressin of saline-loaded rats. In conclusion, chronic clofibrate administration prevented the blood pressure elevation of salt-loaded rats by decreasing sodium balance and reducing thyroid hormone levels. PMID:20981147

Influence of endogenous opiates on the hypotensive action of taurine in DOCA-salt rats.

PubMed

Sato, Y; Fujita, T

1988-12-01

We studied the role of endogenous opiate activation in the hypotensive action of taurine, a sulphur amino acid, in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Previous work had shown that supplementation with 1% taurine reduced blood pressure when given after DOCA-salt hypertension had been established. In the present study, in conscious rats, intraperitoneal injection of naloxone, an opiate antagonist, increased blood pressure in taurine-supplemented DOCA-salt rats, but not in DOCA-salt rats or vehicle-treated control rats. These results suggest that activation of an endogenous opiate might contribute to the hypotensive action of taurine in DOCA-salt hypertensive rats.

Uteroplacental insufficiency temporally exacerbates salt-induced hypertension associated with a reduced natriuretic response in male rat offspring.

PubMed

Gallo, Linda A; Walton, Sarah L; Mazzuca, Marc Q; Tare, Marianne; Parkington, Helena C; Wlodek, Mary E; Moritz, Karen M

2018-03-31

Low weight at birth increases the risk of developing chronic diseases in adulthood A diet that is high in salt is known to elevate blood pressure, which is a major risk factor for cardiovascular and kidney diseases The present study demonstrates that growth restricted male rats have a heightened sensitivity to high dietary salt, in the context of raised systolic blood pressure, reduced urinary sodium excretion and stiffer mesenteric resistance vessels Other salt-induced effects, such as kidney hyperfiltration, albuminuria and glomerular damage, were not exacerbated by being born small The present study demonstrates that male offspring born small have an increased cardiovascular susceptibility to high dietary salt, such that that minimizing salt intake is probably of particular benefit to this at-risk population ABSTRACT: Intrauterine growth restriction increases the risk of developing chronic diseases in adulthood. Lifestyle factors, such as poor dietary choices, may elevate this risk. We determined whether being born small increases the sensitivity to a dietary salt challenge, in the context of hypertension, kidney disease and arterial stiffness. Bilateral uterine vessel ligation or sham surgery (offspring termed Restricted and Control, respectively) was performed on 18-day pregnant Wistar Kyoto rats. Male offspring were allocated to receive a diet high in salt (8% sodium chloride) or remain on standard rat chow (0.52% sodium chloride) from 20 to 26 weeks of age for 6 weeks. Systolic blood pressure (tail-cuff), renal function (24 h urine excretions) and vascular stiffness (pressure myography) were assessed. Restricted males were born 15% lighter than Controls and remained smaller throughout the study. Salt-induced hypertension was exacerbated in Restricted offspring, reaching a peak systolic pressure of ∼175 mmHg earlier than normal weight counterparts. The natriuretic response to high dietary salt in Restricted animals was less than in Controls and may

Differential Stiffening between the Abdominal and Thoracic Aorta: Effect of Salt Loading in Stroke-Prone Hypertensive Rats.

PubMed

Lindesay, George; Bézie, Yvonnick; Ragonnet, Christophe; Duchatelle, Véronique; Dharmasena, Chandima; Villeneuve, Nicole; Vayssettes-Courchay, Christine

2018-06-08

Central artery stiffening is recognized as a cardiovascular risk. The effects of hypertension and aging have been shown in human and animal models but the effect of salt is still controversial. We studied the effect of a high-salt diet on aortic stiffness in salt-sensitive spontaneously hypersensitive stroke-prone rats (SHRSP). Distensibility, distension, and β-stiffness were measured at thoracic and abdominal aortic sites in the same rats, using echotracking recording of the aortic diameter coupled with blood pressure (BP), in SHRSP-salt (5% salted diet, 5 weeks), SHRSP, and normotensive Wistar-Kyoto (WKY) rats. Hemodynamic parameters were measured at BP matched to that of WKY. Histological staining and immunohistochemistry were used for structural analysis. Hemodynamic isobaric parameters in SHRSP did not differ from WKY and only those from the abdominal aorta of SHRSP-salt presented decreased distensibility and increased stiffness compared with WKY and SHRSP. The abdominal and thoracic aortas presented similar thickening, increased fibrosis, and remodeling with no change in collagen content. SHRSP-salt presented a specific increased elastin disarray at the abdominal aorta level but a decrease in elastin content in the thoracic aorta. This study demonstrates the pro-stiffening effect of salt in addition to hypertension; it shows that only the abdominal aorta presents a specific pressure-independent stiffening, in which elastin disarray is likely a key mechanism. © 2018 S. Karger AG, Basel.

Skin Sensitizing Potency of Halogenated Platinum Salts.

EPA Science Inventory

The relationship between occupational exposure to halogenated platinum (Pt) salts and Pt-specific allergic sensitization is well-established. Although human case reports and clinical studies demonstrate that Pt salts are potent skin sensitizers, no studies have been published tha...

Salt loading produces severe renal hemodynamic dysfunction independent of arterial pressure in spontaneously hypertensive rats.

PubMed

Matavelli, Luis C; Zhou, Xiaoyan; Varagic, Jasmina; Susic, Dinko; Frohlich, Edward D

2007-02-01

We have previously shown that salt excess has adverse cardiac effects in spontaneously hypertensive rats (SHR), independent of its increased arterial pressure; however, the renal effects have not been reported. In the present study we evaluated the role of three levels of salt loading in SHR on renal function, systemic and renal hemodynamics, and glomerular dynamics. At 8 wk of age, rats were given a 4% (n = 11), 6% (n = 9), or 8% (n = 11) salt-load diet for the ensuing 8 wk; control rats (n = 11) received standard chow (0.6% NaCl). Rats had weekly 24-h proteinuria and albuminuria quantified. At the end of salt loading, all rats had systemic and renal hemodynamics measured; glomerular dynamics were specially studied by renal micropuncture in the control, 4% and 6% salt-loaded rats. Proteinuria and albuminuria progressively increased by the second week of salt loading in the 6% and 8% salt-loaded rats. Mean arterial pressure increased minimally, and glomerular filtration rate decreased in all salt-loaded rats. The 6% and 8% salt-loaded rats demonstrated decreased renal plasma flow and increased renal vascular resistance and serum creatinine concentration. Furthermore, 4% and 6% salt-loaded rats had diminished single-nephron plasma flow and increased afferent and efferent arteriolar resistances; glomerular hydrostatic pressure also increased in the 6% salt-loaded rats. In conclusion, dietary salt loading as low as 4% dramatically deteriorated renal function, renal hemodynamics, and glomerular dynamics in SHR independent of a minimal further increase in arterial pressure. These findings support the concept of a strong independent causal relationship between salt excess and cardiovascular and renal injury.

Impaired myogenic response and autoregulation of cerebral blood flow is rescued in CYP4A1 transgenic Dahl salt-sensitive rat

PubMed Central

Fan, Fan; Geurts, Aron M.; Murphy, Sydney R.; Pabbidi, Mallikarjuna R.; Jacob, Howard J.

2014-01-01

We have reported that a reduction in renal production of 20-HETE contributes to development of hypertension in Dahl salt-sensitive (SS) rats. The present study examined whether 20-HETE production is also reduced in the cerebral vasculature of SS rats and whether this impairs the myogenic response and autoregulation of cerebral blood flow (CBF). The production of 20-HETE, the myogenic response of middle cerebral arteries (MCA), and autoregulation of CBF were compared in SS, SS-5BN rats and a newly generated CYP4A1 transgenic rat. 20-HETE production was 6-fold higher in cerebral arteries of CYP4A1 and SS-5BN than in SS rats. The diameter of the MCA decreased to 70 ± 3% to 65 ± 6% in CYP4A1 and SS-5BN rats when pressure was increased from 40 to 140 mmHg. In contrast, the myogenic response of MCA isolated from SS rats did not constrict. Administration of a 20-HETE synthesis inhibitor, HET0016, abolished the myogenic response of MCA in CYP4A1 and SS-5BN rats but had no effect in SS rats. Autoregulation of CBF was impaired in SS rats compared with CYP4A1 and SS-5BN rats. Blood-brain barrier leakage was 5-fold higher in the brain of SS rats than in SS-5BN and SS.CYP4A1 rats. These findings indicate that a genetic deficiency in the formation of 20-HETE contributes to an impaired myogenic response in MCA and autoregulation of CBF in SS rats and this may contribute to vascular remodeling and cerebral injury following the onset of hypertension. PMID:25540098

Effects of aging on mineralocorticoid-induced salt appetite in rats

PubMed Central

Beltz, Terry G.; Johnson, Alan Kim

2013-01-01

This work examined the effects of age on salt appetite measured in the form of daily saline (i.e., 0.3 M NaCl) drinking in response to administration of deoxycorticosterone acetate (DOCA; 5 mg/kg body wt) using young (4 mo), “middle-aged” adult (12 mo), and old (30 mo) male Brown Norway rats. Water and sodium intakes, excretions, and balances were determined daily. The salt appetite response was age dependent with “middle-aged” rats ingesting the most saline solution followed in order by young and then old rats. While old rats drank the least saline solution, the amounts of saline ingested still were copious and comprise an unambiguous demonstration of salt appetite in old rats. Middle-aged rats had the highest saline preference ratios of the groups under baseline conditions and throughout testing consistent with an increased avidity for sodium taste. There were age differences in renal handling of water and sodium that were consistent with a renal contribution to the greater saline intakes by middle-aged rats. There was evidence of impaired renal function in old rats, but this did not account for the reduced saline intakes of the oldest rats. PMID:24133100

Heart rate and blood pressure variabilities in salt-sensitive hypertension.

PubMed

Piccirillo, G; Bucca, C; Durante, M; Santagada, E; Munizzi, M R; Cacciafesta, M; Marigliano, V

1996-12-01

In salt-sensitive hypertension, a high sodium intake causes plasma catecholamines to rise and pulmonary baroreceptor plasticity to fall. In salt-sensitive and salt-resistant hypertensive subjects during low and high sodium intakes, we studied autonomic nervous system activity by power spectral analysis of heart rate and arterial pressure variabilities and baroreceptor sensitivity. In all subjects, high sodium intake significantly enhanced the low-frequency power of heart rate and arterial pressures at rest and after sympathetic stress. It also increased heart rate and arterial pressure variabilities. During high sodium intake, salt-sensitive hypertensive subjects had significantly higher low-frequency powers of systolic arterial pressure (7.5 mm Hg2, P < .05) and of heart rate at rest (59.2 +/- 2.4 normalized units [NU], P < .001) than salt-resistant subjects (6.6 +/- 0.3 mm Hg2, 55.0 +/- 3.2 NU) and normotensive control subjects (5.1 +/- 0.5 mm Hg2, 41.6 +/- 2.9 NU). In salt-sensitive subjects, low sodium intake significantly reduced low-frequency normalized units (P < .001) and the ratio of low- to high-power frequency (P < .001). High-sodium intake significantly increased baroreflex sensitivity in control subjects (from 10.0 +/- 0.7 to 17.5 +/- 0.7 ms/mm Hg, P < .001) and salt-resistant subjects (from 6.9 +/- 0.7 to 13.9 +/- 0.9, P < .05) but not in salt-sensitive subjects (7.4 +/- 0.3 to 7.9 +/- 0.4). In conclusion, a high sodium intake markedly enhances cardiac sympathetic activity in salt-sensitive and salt-resistant hypertension. In contrast, although reduced sodium intake lowers arterial pressure and sympathetic activity, it does so only in salt-sensitive subjects. Hence, in salt-resistant subjects, neither arterial pressure nor sympathetic activity depends on salt intake. During a high sodium intake in normotensive subjects and salt-resistant hypertensive subjects, increased sympathetic activity is probably compensated by enhanced baroreflex sensitivity.

Radar RFI at Goldstone DSS 12 and DSS 16

NASA Astrophysics Data System (ADS)

Slobin, S. D.; Peng, T. K.

1990-02-01

Radio frequency interference (RFI) from the DSS 14 Goldstone Solar System Radar (GSSR) was investigated at DSS 12 and DSS 16 with the goal of assisting in the choice of the location of future DSN antennas. Total power measurements at both locations were made at the S-band carrier frequency of 2320 MHz. X-band measurements at the carrier frequency of 8495 MHz could not be made. Exciter-chain output spectrum and klystron output spectrum measurements were made at S- and X-bands using a probable worst-case modulation of the radar signal (short pseudorandom number (PN) code length and short pulse length). Based on these measurements, it is estimated that RFI levels in the DSN receiving bands at both sites (above 10-deg elevation) would be below -192 dBm for a 1-Hz bandwidth

Radar RFI at Goldstone DSS 12 and DSS 16

NASA Technical Reports Server (NTRS)

Slobin, S. D.; Peng, T. K.

1990-01-01

Radio frequency interference (RFI) from the DSS 14 Goldstone Solar System Radar (GSSR) was investigated at DSS 12 and DSS 16 with the goal of assisting in the choice of the location of future DSN antennas. Total power measurements at both locations were made at the S-band carrier frequency of 2320 MHz. X-band measurements at the carrier frequency of 8495 MHz could not be made. Exciter-chain output spectrum and klystron output spectrum measurements were made at S- and X-bands using a probable worst-case modulation of the radar signal (short pseudorandom number (PN) code length and short pulse length). Based on these measurements, it is estimated that RFI levels in the DSN receiving bands at both sites (above 10-deg elevation) would be below -192 dBm for a 1-Hz bandwidth

Prenatal and early postnatal dietary sodium restriction sensitizes the adult rat to amphetamines.

PubMed

McBride, Shawna M; Culver, Bruce; Flynn, Francis W

2006-10-01

Acute sodium deficiency sensitizes adult rats to psychomotor effects of amphetamine. This study determined whether prenatal and early life manipulation of dietary sodium sensitized adult offspring to psychomotor effects of amphetamine (1 or 3 mg/kg ip) in two strains of rats. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) dams were fed chow containing low NaCl (0.12%; LN), normal NaCl (1%; NN), or high NaCl (4%; HN) throughout breeding, gestation, and lactation. Male offspring were maintained on the test diet for an additional 3 wk postweaning and then fed standard chow thereafter until testing began. Overall, blood pressure (BP), total fluid intake, salt preference, and adrenal gland weight were greater in SHR than in WKY. WKY LN offspring had greater water intake and adrenal gland weight than did WKY NN and HN offspring, whereas WKY HN offspring had increased BP, salt intake, and salt preference compared with other WKY offspring. SHR HN offspring also had increased BP compared with other SHR offspring; all other measures were similar for SHR offspring. The low-dose amphetamine increased locomotor and stereotypical behavior compared with baseline and saline injection in both WKY and SHR offspring. Dietary sodium history affected the rats' psychomotor response to the higher dose of amphetamine. Injections of 3 mg/kg amphetamine in both strains produced significantly more behavioral activity in the LN offspring than in NN and HN offspring. These results show that early life experience with low-sodium diets produce long-term changes in adult rats' behavioral responses to amphetamine.

Salt sensitivity of children with low birth weight.

PubMed

Simonetti, Giacomo D; Raio, Luigi; Surbek, Daniel; Nelle, Mathias; Frey, Felix J; Mohaupt, Markus G

2008-10-01

Compromised intrauterine fetal growth leading to low birth weight (<2500 g) is associated with adulthood renal and cardiovascular disease. The aim of this study was to assess the effect of salt intake on blood pressure (salt sensitivity) in children with low birth weight. White children (n=50; mean age: 11.3+/-2.1 years) born with low (n=35) or normal (n=15) birth weight and being either small or appropriate for gestational age (n=25 in each group) were investigated. The glomerular filtration rate was calculated using the Schwartz formula, and renal size was measured by ultrasound. Salt sensitivity was assigned if mean 24-hour blood pressure increased by >or=3 mm Hg on a high-salt diet as compared with a controlled-salt diet. Baseline office blood pressure was higher and glomerular filtration rate lower in children born with low birth weight as compared with children born at term with appropriate weight (P<0.05). Salt sensitivity was present in 37% and 47% of all of the low birth weight and small for gestational age children, respectively, higher even than healthy young adults from the same region. Kidney length and volume (both P<0.0001) were reduced in low birth weight children. Salt sensitivity inversely correlated with kidney length (r(2)=0.31; P=0.005) but not with glomerular filtration rate. We conclude that a reduced renal mass in growth-restricted children poses a risk for a lower renal function and for increased salt sensitivity. Whether the changes in renal growth are causative or are the consequence of the same abnormal "fetal programming" awaits clarification.

Bamboo salt attenuates CCl4-induced hepatic damage in Sprague-Dawley rats

PubMed Central

Zhao, Xin; Song, Jia-Le; Kil, Jeung-Ha

2013-01-01

Bamboo salt, a Korean folk medicine, is prepared with solar salt (sea salt) and baked several times at high temperatures in a bamboo case. In this study, we compared the preventive effects of bamboo salt and purified and solar salts on hepatic damage induced by carbon tetrachloride in Sprague-Dawley rats. Compared with purified and solar salts, bamboo salts prevented hepatic damage in rats, as evidenced by significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase (P < 0.05). Bamboo salt (baked 9×) triggered the greatest reduction in these enzyme levels. In addition, it also reduced the levels of the proinflammatory cytokines interleukin (IL)-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. Histopathological sections of liver tissue demonstrated the protective effect of bamboo salt, whereas sections from animals treated with the other salt groups showed a greater degree of necrosis. We also performed reverse transcription-polymerase chain reaction and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-α, and IL-1β in rat liver tissues. Bamboo salt induced a significant decrease (~80%) in mRNA and protein expression levels of COX-2, iNOS, TNF-α, and IL-1β, compared with the other salts. Thus, we found that baked bamboo salt preparations could prevent CCl4-induced hepatic damage in vivo. PMID:23964314

Salt appetite of adrenalectomized rats after a lesion of the SFO.

PubMed

Wilson, Wendy L; Starbuck, Elizabeth M; Fitts, Douglas A

2002-11-15

Circumventricular organs such as the subfornical organ (SFO) may mediate the effects of circulating angiotensin (ANG) II on salt appetite under conditions of sodium depletion in the rat. We studied the effects of an electrolytic lesion of SFO on salt appetite after adrenalectomy (ADX) in Long-Evans rats. The SFO lesion had no effect on saline intake, but it did abolish water intake after acute peripheral treatments with 2 mg/kg of captopril or a 10 mg/kg of furosemide. These findings contrast with other recent data from this laboratory demonstrating large reductions in salt appetite in adrenal-intact rats with lesions of either SFO or the organum vasculosum laminae terminalis during acute iv infusions of ANG II. Thus, the SFO may contribute to the salt appetite response to circulating ANG II, but it is not essential for the response to adrenalectomy. Copyright 2002 Elsevier Science B.V.

DSS-24 microwave holography measurements

NASA Technical Reports Server (NTRS)

Rochblatt, D. J.; Withington, P. M.; Jackson, H. J.

1995-01-01

The JPL DSN Microwave Antenna Holography System (MAHST) was applied to the newly constructed DSS-24 34-m beam-waveguide antenna at Goldstone, California. The application of MAHST measurements and corrections at DSS 24 provided the critical RF performance necessary to not only meet the project requirements and goals, but to surpass them. A performance increase of 0.35 dB at X-band (8.45 GHz) and 4.9 dB at Ka-band (32 GHz) was provided by MAHST, resulting in peak efficiencies of 75.25 percent at X-band and 60.6 percent at Ka-band (measured from the Cassegrain focus at f1). The MAHST enabled setting the main reflector panels of DSS 24 to 0.25-mm rms, making DSS 24 the highest precision antenna in the NASA/JPL DSN. The precision of the DSS-24 antenna (diameter/rms) is 1.36 x 10(exp 5), and its gain limit is at 95 GHz.

The altered balance between sympathetic nervous system and nitric oxide in salt hypertensive Dahl rats: ontogenetic and F2 hybrid studies.

PubMed

Dobesová, Zdena; Kunes, Jaroslav; Zicha, Josef

2002-05-01

We have demonstrated earlier that the nitric oxide (NO) system is not able to counterbalance effectively the hyperactivity of the sympathetic nervous system (SNS) in salt hypertension of young Dahl rats in which augmented superoxide anion formation lowers NO bioavailability. The aim of the present study was to determine whether SNS hyperactivity and/or relative NO deficiency are also present in salt hypertension elicited in adult Dahl rats, and whether they are associated with blood pressure (BP) in the F2 population of Dahl rats. The contribution of major vasoactive systems [renin-angiotensin system (RAS), SNS and NO] and superoxide anions to BP maintenance was studied in SS/Jr rats in which salt hypertension was induced either in adulthood or in youth (8% NaCl diet from the age of 12 or 4 weeks). The contribution of particular vasoactive systems was also investigated in 122 young salt-loaded F2hybrids [derived from salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahl rats] which were fed a high-salt diet (8% NaCl) for 6 weeks after weaning. Mean arterial pressure (MAP) was measured in conscious animals subjected to acute consecutive blockade of RAS (captopril 10 mg/kg i.v.), SNS (pentolinium 5 mg/kg i.v.) and NO synthase (l-NAME 30 mg/kg i.v.). Dahl rats with salt hypertension induced in adulthood were also characterized by enhanced pentolinium-induced BP fall (DeltaMAPpento), but their residual BP (recorded after the blockade of both RAS and SNS) was unaltered, in contrast to its elevation seen in young salt-hypertensive rats. The BP rise after NO synthase inhibition by l-NAME (DeltaMAPL-NAME), which was substantially greater in adult than in young hypertensive rats, was not enhanced by superoxide scavenging with tempol in adult hypertensive animals, in which this drug elicited a moderate BP reduction only. Basal MAP of young salt-loaded F2 hybrids was positively associated not only with DeltaMAPpento (P < 0.0001) and residual BP (P < 0.001) but also with

Prenatal programming of renal salt wasting resets postnatal salt appetite, which drives food intake in the rat.

PubMed

Alwasel, Saleh H; Barker, David J P; Ashton, Nick

2012-03-01

Sodium retention has been proposed as the cause of hypertension in the LP rat (offspring exposed to a maternal low-protein diet in utero) model of developmental programming because of increased renal NKCC2 (Na+/K+/2Cl- co-transporter 2) expression. However, we have shown that LP rats excrete more rather than less sodium than controls, leading us to hypothesize that LP rats ingest more salt in order to maintain sodium balance. Rats were fed on either a 9% (low) or 18% (control) protein diet during pregnancy; male and female offspring were studied at 4 weeks of age. LP rats of both sexes held in metabolism cages excreted more sodium and urine than controls. When given water to drink, LP rats drank more and ate more food than controls, hence sodium intake matched excretion. However, when given a choice between saline and water to drink, the total volume of fluid ingested by LP rats fell to control levels, but the volume of saline taken was significantly larger [3.8±0.1 compared with 8.8±1.3 ml/24 h per 100 g of body weight in control and LP rats respectively; P<0.001]. Interestingly food intake also fell to control levels. Total body sodium content and ECF (extracellular fluid) volumes were greater in LP rats. These results show that prenatal programming of renal sodium wasting leads to a compensatory increase in salt appetite in LP rats. We speculate that the need to maintain salt homoeostasis following malnutrition in utero stimulates greater food intake, leading to accelerated growth and raised BP (blood pressure).

Induction of nasal and nasopharyngeal tumours in Sprague-Dawley rats fed with Chinese salted fish.

PubMed

Zheng, X; Luo, Y; Christensson, B; Drettner, B

1994-01-01

Epidemiological studies have implied that Chinese salted fish is a human nasopharyngeal carcinogen. In the present study, 162 Sprague-Dawley rats were randomly assigned to one of four experimental groups. Rats in groups 1 (n = 41) and 3 (n = 40) were exposed to salted fish from birth through the breast feeding period by giving the maternal rats a diet containing 10% and 5% salted fish, respectively, later feeding the rats with pellets containing 10% and 5% of salted fish respectively. In group 2, the rats (n = 41) were given pellets containing 10% of salted fish from 6 weeks of age. Rats in group 4 (n = 40), serving as controls, were only given ordinary pellets. Three rats had nasopharyngeal tumours, 2 from group 1 had a poorly differentiated carcinoma and a squamous cell carcinoma. One rat from group 2 had a squamous cell carcinoma. Four rats had nasal tumours, one fibrosarcoma and one adenocarcinoma were found in rats from group 1. One rhabdomyosarcoma was found in group 2, and one soft tissue sarcoma was found in a rat in group 3. No nasal or nasopharyngeal tumours appeared in the control group. The difference in the occurrence of malignant nasal and nasopharyngeal tumours among the four experimental groups was statistically significant (one tailed p for trend = 0.041). The frequency of tumours appearing in other organs such as the breast, kidney, lung, liver and brain was not significantly different between the salted fish treated groups and the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Nicotine impairs reflex renal nerve and respiratory activity in deoxycorticosterone acetate-salt rats.

PubMed

Whitescarver, S A; Roberts, A M; Stremel, R W; Jimenez, A E; Passmore, J C

1991-02-01

Smoking exacerbates the increase in arterial pressure in hypertension. The effect of nicotine on the baroreceptor-mediated reflex responses of renal nerve activity (RNA), heart rate, and respiratory activity (minute diaphragmatic activity [MDA]) after bolus injections of phenylephrine was compared in deoxycorticosterone acetate (DOCA)-salt sensitive and normotensive rats. Osmotic minipumps that dispensed either nicotine (2.4 mg/kg/day) or saline were implanted in DOCA and normotensive rats for 18 days. Anesthetized DOCA-nicotine, DOCA-saline, control-nicotine, and control-saline rats had mean arterial pressures (MAP) of 117 +/- 3, 110 +/- 9, 90 +/- 3, and 89 +/- 5 mm Hg, respectively. Nicotine decreased the sensitivity (p less than 0.05) of baroreceptor reflex control of RNA (% delta RNA/delta MAP) in the DOCA-nicotine rats (-0.92 +/- 0.08) compared with the DOCA-saline (-1.44 +/- 0.16), control-nicotine (-1.45 +/- 0.08), or control-saline (-1.45 +/- 0.21) rats. The reflex decrease in respiratory activity (% delta MDA/delta MAP x 100) was impaired (p less than 0.01) in both control-nicotine (-24.5 +/- 3.3) and DOCA-nicotine (-18.2 +/- 4.6) rats compared with control-saline (-59.2 +/- 9.1) and DOCA-saline (-52.5 +/- 9.9) rats. The reflex decrease in heart rate (absolute delta HR/delta MAP) in both DOCA-nicotine (1.56 +/- 0.17) and control-nicotine (1.54 +/- 0.24) rats was augmented compared with DOCA-saline and control-saline rats (0.91 +/- 0.12 and 0.97 +/- 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)

Propolis from Different Geographic Origins Suppress Intestinal Inflammation in a Model of DSS-Induced Colitis is Associated with Decreased Bacteroides spp. in the Gut.

PubMed

Wang, Kai; Jin, Xiaolu; Li, Qiangqiang; Sawaya, Alexandra Christine Helena Frankland; Leu, Richard K Le; Conlon, Michael A; Wu, Liming; Hu, Fuliang

2018-06-11

Dietary supplementation with polyphenol-rich propolis can protect against experimentally-induced colitis. We examined whether different polyphenol compositions of Chinese propolis (CP) and Brazilian propolis (BP) influences their ability to protect against dextran sulfate sodium (DSS)-induced colitis in rats. HPLC-DAD/Q-TOF-MS analysis confirmed that polyphenol compositions of CP and BP were dissimilar. Rats were given CP or BP by gavage (300 mg/kg body weight) throughout the study, starting 1 week prior to DSS treatment for 1 week followed by 3 d without DSS. CP and BP significantly reduced the colitis disease activity index relative to controls not receiving propolis, prevented significant DSS-induced colonic tissue damage and increased resistance to DSS-induced colonic oxidative stress as shown by reduced malonaldehyde levels and increased T-AOC levels. CP and BP significantly reduced DSS-induced colonic apoptosis. Colonic inflammatory markers IL-1β, IL-6 and MCP-1 were suppressed by CP and BP, whereas only BP induced expression of TGF-β. CP, not BP, increased the diversity and richness of gut microbiota populations. Both forms of propolis significantly reduced populations of Bacteroides spp. Despite the dissimilar polyphenol compositions of CP and BP, their ability to protect against DSS-induced colitis is similar. Nevertheless, some different physiological impacts were observed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Intestinal anti-inflammatory activity of combined quercitrin and dietary olive oil supplemented with fish oil, rich in EPA and DHA (n-3) polyunsaturated fatty acids, in rats with DSS-induced colitis.

PubMed

Camuesco, D; Comalada, M; Concha, A; Nieto, A; Sierra, S; Xaus, J; Zarzuelo, A; Gálvez, J

2006-06-01

Previous studies have described the intestinal anti-inflammatory effects exerted by the bioflavonoid quercitrin (QR) and by an n-3 polyunsaturated fatty acids (PUFA)-enriched diet in experimental models of rat colitis. The aim of the present study was to test if the combination of both treatments would result in an improvement in the intestinal anti-inflammatory effect achieved separately. Colitis was induced in female Wistar rats by incorporating dextran sodium sulfate (DSS) in drinking water at 5% (w/v) for 5 days and at 2% (w/v) for the following 10 days. Five groups of rats (n=10) were used: two of them received an olive-oil-based diet with fish oil, rich in n-3 PUFA (FO diet) for 2 weeks before colitis induction and until the end of the experiment, and one of those also was administered daily QR (1mg/kg, PO), starting when DSS concentration was changed. DSS colitis was induced in other two groups fed with standard rat diet, one of them being administered QR as before. A non-colitic group fed standard diet was also included. After that period, the rats were sacrificed and colonic damage was assessed both histologically and biochemically. The concurrent administration of FO diet and QR exhibited an intestinal anti-inflammatory effect, as evidenced by a significant improvement of all biochemical parameters of colonic inflammation assayed in comparison with non-treated colitic rats. Thus, both colonic myeloperoxidase (MPO) and alkaline phosphatase (AP) activities were significantly reduced compared with untreated colitic rats. In addition, a complete restoration of colonic glutathione content, which was depleted as a consequence of the colonic insult, was obtained in rats treated with QR plus FO diet; this content was even higher than that obtained when colitic rats were treated with FO diet alone. When compared with the control colitic group, the combined treatment was also associated with a lower colonic nitric oxide synthase and cyclooxygenase-2 expression as

Amelioration of cardio-renal injury with aging in dahl salt-sensitive rats by H2-enriched electrolyzed water

PubMed Central

2013-01-01

Abstract Recent studies have revealed the biological effects of H2 in suppressing organ injuries due to acute inflammation and oxidative stress. Dahl salt-sensitive (SS) rats naturally develop elevated blood pressure (BP) and kidney injury with aging. The present study examined the effect of long-term supplementation of H2 in drinking water on age-related changes. Four-week-old male Dahl SS rats were fed 3 types of water (n = 30 each) for up to 48 weeks: filtered water (FW), water with a high H2 content (492.5 ppb) obtained with water electrolysis (EW), or dehydrogenated EW (DW). Animals were subjected to histological analysis at 16, 24, and 48 weeks. The FW group showed progressive BP elevation and increases in albuminuria and cardiac remodeling during the course of treatment. Histologically, there were significant changes as a function of aging, i.e., glomerular sclerosis with tubulointerstitial fibrosis in the kidney, and increased cardiomyocyte diameter with interstitial fibrosis in the heart at 48 weeks. These changes were related to the enhanced inflammation and oxidative stress in the respective organs. However, there were no striking differences in BP among the groups, despite histological alterations in the EW group being significantly decreased when compared to FW and DW in both organs, with concurrently lower oxidative stress and inflammatory markers at 48 weeks. Conclusion Long-term ad libitum consumption of H2-enriched electrolyzed water can ameliorate the processes of kidney injury and cardiac remodeling with aging in Dahl SS rats by suppressing, at least partly, elevated inflammation and oxidative stress. PMID:24289332

Increased Dietary Salt Changes Baroreceptor Sensitivity and Intrarenal Renin-Angiotensin System in Goldblatt Hypertension.

PubMed

Shimoura, Caroline G; Lincevicius, Gisele S; Nishi, Erika E; Girardi, Adriana C C; Simon, Karin A; Bergamaschi, Cassia T; Campos, Ruy R

2017-01-01

Renovascular hypertension (2-kidney 1-clip model (2K1C)) is characterized by renin-angiotensin system (RAS) activation. Increased Angiotensin II (AngII) leads to sympathoexcitation, oxidative stress, and alterations in sodium and water balance. The aim of this study was to evaluate whether a discrete increase in sodium chloride intake in 2K1C rats leads to changes in cardiovascular and autonomic function, oxidative stress, and renin angiotensin aldosterone system. After 4 weeks of induction of hypertension, rats were fed a normal sodium diet (0.4% NaCl) or a high-sodium diet (2% NaCl) for 2 consecutive weeks. Experiments were carried out for 6 weeks after clipping. Mean arterial pressure (MAP), renal sympathetic nerve activity (rSNA), arterial baroreflex control of rSNA, and heart rate (HR) were assessed. Thiobarbituric acid reactive substances and glutathione were measured as indicators of systemic oxidative stress. Angiostensin-converting enzyme (ACE), ACE2, and angiotensinogen were evaluated in clipped and unclipped kidneys as also urinary angiotensinogen and plasma renin activity. Angiotensinogen, plasma renin activity (PRA) and angiotensin-converting enzyme (ACE) and ACE2 in clipped and unclipped kidneys were evaluated. High-sodium diet did not change systemic oxidative stress, and basal values of MAP, HR, or rSNA; however, increased renal (-0.7±0.2 vs. -1.5±0.1 spikes/s/mm Hg) and cardiac (-0.9±0.14 vs. -1.5±0.14 bpm/mm Hg) baroreceptor reflex sensitivity in 2K1C rats. Although there was no alteration in PRA, a high-salt diet significantly decreased urinary angiotensinogen, ACE, and ACE2 expressions in the clipped and unclipped kidneys. Increased arterial baroreceptor control associated with a suppression of the intrarenal RAS in the 2K1C rats on high-salt diet provide a salt-resistant effect on hypertension and sympathoexcitation in renovascular hypertensive rats. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please

Proteomic and phosphoproteomic analysis of renal cortex in a salt-load rat model of advanced kidney damage

PubMed Central

Jiang, Shaoling; He, Hanchang; Tan, Lishan; Wang, Liangliang; Su, Zhengxiu; Liu, Yufeng; Zhu, Hongguo; Zhang, Menghuan; Hou, Fan Fan; Li, Aiqing

2016-01-01

Salt plays an essential role in the progression of chronic kidney disease and hypertension. However, the mechanisms underlying pathogenesis of salt-induced kidney damage remain largely unknown. Here, Sprague-Dawley rats, that underwent 5/6 nephrectomy (5/6Nx, a model of advanced kidney damage) or sham operation, were treated for 2 weeks with a normal or high-salt diet. We employed aTiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for proteomic and phosphoproteomic profiling of the renal cortex. We found 318 proteins differentially expressed in 5/6Nx group relative to sham group, and 310 proteins significantly changed in response to salt load in 5/6Nx animals. Totally, 1810 unique phosphopeptides corresponding to 550 phosphoproteins were identified. We identified 113 upregulated and 84 downregulated phosphopeptides in 5/6Nx animals relative to sham animals. Salt load induced 78 upregulated and 91 downregulated phosphopeptides in 5/6Nx rats. The differentially expressed phospholproteins are important transporters, structural molecules, and receptors. Protein-protein interaction analysis revealed that the differentially phosphorylated proteins in 5/6Nx group, Polr2a, Srrm1, Gsta2 and Pxn were the most linked. Salt-induced differential phosphoproteins, Myh6, Lmna and Des were the most linked. Altered phosphorylation levels of lamin A and phospholamban were validated. This study will provide new insight into pathogenetic mechanisms of chronic kidney disease and salt sensitivity. PMID:27775022

Salt-Stress Response Mechanisms Using de Novo Transcriptome Sequencing of Salt-Tolerant and Sensitive Corchorus spp. Genotypes

PubMed Central

Yang, Zemao; Lu, Ruike; Dai, Zhigang; Yan, An; Tang, Qing; Cheng, Chaohua; Xu, Ying; Yang, Wenting; Su, Jianguang

2017-01-01

High salinity is a major environmental stressor for crops. To understand the regulatory mechanisms underlying salt tolerance, we conducted a comparative transcriptome analysis between salt-tolerant and salt-sensitive jute (Corchorus spp.) genotypes in leaf and root tissues under salt stress and control conditions. In total, 68,961 unigenes were identified. Additionally, 11,100 unigenes (including 385 transcription factors (TFs)) exhibited significant differential expression in salt-tolerant or salt-sensitive genotypes. Numerous common and unique differentially expressed unigenes (DEGs) between the two genotypes were discovered. Fewer DEGs were observed in salt-tolerant jute genotypes whether in root or leaf tissues. These DEGs were involved in various pathways, such as ABA signaling, amino acid metabolism, etc. Among the enriched pathways, plant hormone signal transduction (ko04075) and cysteine/methionine metabolism (ko00270) were the most notable. Eight common DEGs across both tissues and genotypes with similar expression profiles were part of the PYL-ABA-PP2C (pyrabactin resistant-like/regulatory components of ABA receptors-abscisic acid-protein phosphatase 2C). The methionine metabolism pathway was only enriched in salt-tolerant jute root tissue. Twenty-three DEGs were involved in methionine metabolism. Overall, numerous common and unique salt-stress response DEGs and pathways between salt-tolerant and salt-sensitive jute have been discovered, which will provide valuable information regarding salt-stress response mechanisms and help improve salt-resistance molecular breeding in jute. PMID:28927022

Protective effects of AT1-receptor blocker and CA antagonist combination on renal function in salt loaded spontaneously hypertensive rats.

PubMed

Gjorgjievska, K; Zafirov, D; Jurhar-Pavlova, M; Cekovska, S; Atanasovska, E; Pavlovska, K; Zendelovska, D

2015-01-01

Salt sensitive hypertension is known to be a contributing factor for the progression of kidney disease. This study was undertaken to investigate the role of excessive dietary salt on renal function and to evaluate the effect of valsartan and amlodipin given as a combination therapy on blood pressure and parameters specific to the renal function in salt loaded SHR rats. 48 male SHR rats at age of 20 weeks and body weight ranging between 270-350 g were used. SHR rats were divided into 3 groups: control group of rats -SHRC (n = 16) given tab water ad libitum and two salt treated groups in which tab water was replaced with a solution of NaCl (1%) from age of 8 weeks given ad libitum: SHRVAL+AMLO group (n = 16) where investigated drugs were administered at a dose of 10 mg/kg/ b.w. (valsartan) and 5 mg/kg/ b.w. (amlodipin) by gavage and SHR NaCl group (n = 16) that received saline in the same volume and the same time intervals as the SHRVAL+AMLO group. For a period of 12 weeks we have investigated the effect of the VAL+AMLO drug combination on systolic blood pressure (SBP), body weight and renal function tests. Salt loading with 1% solution in the SHR NaCl group has lead to significant increase of blood pressure, proteinuria and decrease in creatinine clearance. Combined treatment with AT1 receptor blocker and calcium antagonist has managed to control blood pressure and ameliorated renal damage.

Salt stress-induced changes in antioxidative defense system and proteome profiles of salt-tolerant and sensitive Frankia strains.

PubMed

Srivastava, Amrita; Singh, Anumeha; Singh, Satya S; Mishra, Arun K

2017-04-16

An appreciation of comparative microbial survival is most easily done while evaluating their adaptive strategies during stress. In the present experiment, antioxidative and whole cell proteome variations based on spectrophotometric analysis and SDS-PAGE and 2-dimensional gel electrophoresis have been analysed among salt-tolerant and salt-sensitive Frankia strains. This is the first report of proteomic basis underlying salt tolerance in these newly isolated Frankia strains from Hippophae salicifolia D. Don. Salt-tolerant strain HsIi10 shows higher increment in the contents of superoxide dismutase, catalase and ascorbate peroxidase as compared to salt-sensitive strain HsIi8. Differential 2-DGE profile has revealed differential profiles for salt-tolerant and salt-sensitive strains. Proteomic confirmation of salt tolerance in the strains with inbuilt efficiency of thriving in nitrogen-deficient locales is a definite advantage for these microbes. This would be equally beneficial for improvement of soil nitrogen status. Efficient protein regulation in HsIi10 suggests further exploration for its potential use as biofertilizer in saline soils.

Dietary Salt Exacerbates Isoproterenol-induced Cardiomyopathy in Rats

EPA Science Inventory

Spontaneously Hypertensive Heart Failure rats (SHHFs) take far longer to develop compensated heart failure and congestive decompensation than common surgical models of heart failure. Isoproterenol (ISO) infusion can accelerate cardiomyopathy in young SHHFs, while dietary salt loa...

Differential neural representation of oral ethanol by central taste-sensitive neurons in ethanol-preferring and genetically heterogeneous rats

PubMed Central

Wilson, David M.; Brasser, Susan M.

2011-01-01

In randomly bred rats, orally applied ethanol stimulates neural substrates for appetitive sweet taste. To study associations between ethanol's oral sensory characteristics and genetically mediated ethanol preference, we made electrophysiological recordings of oral responses (spike density) by taste-sensitive nucleus tractus solitarii neurons in anesthetized selectively bred ethanol-preferring (P) rats and their genetically heterogeneous Wistar (W) control strain. Stimuli (25 total) included ethanol [3%, 5%, 10%, 15%, 25%, and 40% (vol/vol)], a sucrose series (0.01, 0.03, 0.1, 0.3, 0.5, and 1 M), and other sweet, salt, acidic, and bitter stimuli; 50 P and 39 W neurons were sampled. k-means clustering applied to the sucrose response series identified cells showing high (S1) or relatively low (S0) sensitivity to sucrose. A three-way factorial analysis revealed that activity to ethanol was influenced by a neuron's sensitivity to sucrose, ethanol concentration, and rat line (P = 0.01). Ethanol produced concentration-dependent responses in S1 neurons that were larger than those in S0 cells. Although responses to ethanol by S1 cells did not differ between lines, neuronal firing rates to ethanol in S0 cells increased across concentration only in P rats. Correlation and multivariate analyses revealed that ethanol evoked responses in W neurons that were strongly and selectively associated with activity to sweet stimuli, whereas responses to ethanol by P neurons were not easily associated with activity to representative sweet, sodium salt, acidic, or bitter stimuli. These findings show differential central neural representation of oral ethanol between genetically heterogeneous rats and P rats genetically selected to prefer alcohol. PMID:21918002

Differential neural representation of oral ethanol by central taste-sensitive neurons in ethanol-preferring and genetically heterogeneous rats.

PubMed

Lemon, Christian H; Wilson, David M; Brasser, Susan M

2011-12-01

In randomly bred rats, orally applied ethanol stimulates neural substrates for appetitive sweet taste. To study associations between ethanol's oral sensory characteristics and genetically mediated ethanol preference, we made electrophysiological recordings of oral responses (spike density) by taste-sensitive nucleus tractus solitarii neurons in anesthetized selectively bred ethanol-preferring (P) rats and their genetically heterogeneous Wistar (W) control strain. Stimuli (25 total) included ethanol [3%, 5%, 10%, 15%, 25%, and 40% (vol/vol)], a sucrose series (0.01, 0.03, 0.1, 0.3, 0.5, and 1 M), and other sweet, salt, acidic, and bitter stimuli; 50 P and 39 W neurons were sampled. k-means clustering applied to the sucrose response series identified cells showing high (S(1)) or relatively low (S(0)) sensitivity to sucrose. A three-way factorial analysis revealed that activity to ethanol was influenced by a neuron's sensitivity to sucrose, ethanol concentration, and rat line (P = 0.01). Ethanol produced concentration-dependent responses in S(1) neurons that were larger than those in S(0) cells. Although responses to ethanol by S(1) cells did not differ between lines, neuronal firing rates to ethanol in S(0) cells increased across concentration only in P rats. Correlation and multivariate analyses revealed that ethanol evoked responses in W neurons that were strongly and selectively associated with activity to sweet stimuli, whereas responses to ethanol by P neurons were not easily associated with activity to representative sweet, sodium salt, acidic, or bitter stimuli. These findings show differential central neural representation of oral ethanol between genetically heterogeneous rats and P rats genetically selected to prefer alcohol.

Effect of fluid and salt supplements in preventing the development of "osteopenia" in hypokinetic rats

NASA Astrophysics Data System (ADS)

Zorbas, Y. G.; Federenko, Y. F.; Togawa, M. N.

It has been suggested that a daily intake of fluid and salt supplements may be used to prevent bone demineralization in human subjects after prolonged exposure to hypokinesia (diminished muscular activity). Thus, the objective of this investigation was to evaluate the effect of fluid and salt supplementation in the prevention of development of osteoporosis in 64 Wistar rats with an initial body weight of 339-345 g, after exposure to 90 days of hypokinesia. They divided into 4 equal groups: the first group of rats placed under ordinary vivarium conditions and served as vivarium control; the second group were also placed under ordinary vivarium conditions but received daily fluid and salt supplements; the third group were subjected to pure hypokinesia, i.e. without the use of any preventive measures; and the fourth group were submitted to hypokinesia and received daily fluid and salt supplements. For the simulation of the hypokinetic effect the experimental group of rats were kept in small, individual, wooden cages. Through the experimental period the second and fourth group of rats received 8 ml/100 g body wt water and 5 ml 100 g body wt NaCl daily. By the end of the experimental period the animals were decapitated and the spongy matter of tibia and vertebrae of the rats were examined for changes referable to osteoporosis. It was found that the daily intake of fluid and salt supplements caused an increase in the volume density of primary spongiosa of bones. It was concluded that a daily intake of fluid and salt supplements may be used to prevent the development of osteoporosis in rats subjected to prolonged motor activity restriction.

DSS range delay calibrations: Current performance level

NASA Technical Reports Server (NTRS)

Spradlin, G. L.

1976-01-01

A means for evaluating Deep Space Station (DSS) range delay calibration performance was developed. Inconsistencies frequently noted in these data are resolved. Development of the DSS range delay data base is described. The data base is presented with comments regarding apparent discontinuities. Data regarding the exciter frequency dependence of the delay values are presented. The improvement observed in the consistency of current DSS range delay calibration data over the performance previously observed is noted.

Salt appetite is reduced by a single experience of drinking hypertonic saline in the adult rat.

PubMed

Greenwood, Michael P; Greenwood, Mingkwan; Paton, Julian F R; Murphy, David

2014-01-01

Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions.

Salt Appetite Is Reduced by a Single Experience of Drinking Hypertonic Saline in the Adult Rat

PubMed Central

Greenwood, Michael P.; Greenwood, Mingkwan; Paton, Julian F. R.; Murphy, David

2014-01-01

Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions. PMID:25111786

Interdependency of Reactive Oxygen Species generating and scavenging system in salt sensitive and salt tolerant cultivars of rice.

PubMed

Kaur, Navdeep; Dhawan, Manish; Sharma, Isha; Pati, Pratap Kumar

2016-06-10

Salinity stress is a major constrain in the global rice production and hence serious efforts are being undertaken towards deciphering its remedial strategies. The comparative analysis of differential response of salt sensitive and salt tolerant lines is a judicious approach to obtain essential clues towards understanding the acquisition of salinity tolerance in rice plants. However, adaptation to salt stress is a fairly complex process and operates through different mechanisms. Among various mechanisms involved, the reactive oxygen species mediated salinity tolerance is believed to be critical as it evokes cascade of responses related to stress tolerance. In this background, the present paper for the first time evaluates the ROS generating and the scavenging system in tandem in both salt sensitive and salt tolerant cultivars of rice for getting better insight into salinity stress adaptation. Comparative analysis of ROS indicates the higher level of hydrogen peroxide (H2O2) and lower level of superoxide ions (O(2-)) in the salt tolerant as compared to salt sensitive cultivars. Specific activity of ROS generating enzyme, NADPH oxidase was also found to be more in the tolerant cultivars. Further, activities of various enzymes involved in enzymatic and non enzymatic antioxidant defence system were mostly higher in tolerant cultivars. The transcript level analysis of antioxidant enzymes were in alignment with the enzymatic activity. Other stress markers like proline were observed to be higher in tolerant varieties whereas, the level of malondialdehyde (MDA) equivalents and chlorophyll content were estimated to be more in sensitive. The present study showed significant differences in the level of ROS production and antioxidant enzymes activities among sensitive and tolerant cultivars, suggesting their possible role in providing natural salt tolerance to selected cultivars of rice. Our study demonstrates that the cellular machinery for ROS production and scavenging system

Simultaneous Determination and Pharmacokinetic Comparisons of Multi-Ingredients after Oral Administration of Radix Salviae Miltiorrhizae Extract, Hawthorn Extract, and a Combination of Both Extracts to Rats

PubMed Central

Liu, Yu-Qiang; Cai, Qian; Liu, Chang; Bao, Feng-Wei; Zhang, Zhen-Qiu

2014-01-01

A simple and sensitive HPLC method was developed for simultaneous determination of danshensu (DSS), rosmarinic acid (RA), lithospermic acid (LA), salvianolic acid B (SAB), and hyperoside (HP) in rat plasma. This method validated was successfully applied to the pharmacokinetic study of the main active ingredients after oral administration of Radix Salviae Miltiorrhizae extract (SME), hawthorn extract (HTE), and a combination of both extracts (2.5 : 1) to rats. The results indicated that there have been great differences in pharmacokinetics between a single extract and a combination of both extracts. A combination of both extracts can enhance their bioavailabilities and delay the elimination of SAB and DSS in rats. PMID:24660090

Vectorial transport of bile salts across MDCK cells expressing both rat Na+-taurocholate cotransporting polypeptide and rat bile salt export pump.

PubMed

Mita, Sachiko; Suzuki, Hiroshi; Akita, Hidetaka; Stieger, Bruno; Meier, Peter J; Hofmann, Alan F; Sugiyama, Yuichi

2005-01-01

Bile salts are predominantly taken up by hepatocytes via the basolateral Na(+)-taurocholate cotransporting polypeptide (NTCP/SLC10A1) and secreted into the bile by the bile salt export pump (BSEP/ABCB11). In the present study, we transfected rat Ntcp and rat Bsep into polarized Madin-Darby canine kidney cells and characterized the transport properties of these cells for eight bile salts. Immunohistochemical staining demonstrated that Ntcp was expressed at the basolateral domains, whereas Bsep was expressed at the apical domains. Basal-to-apical transport of taurocholate across the monolayer expressing only Ntcp and that coexpressing Ntcp/Bsep was observed, whereas the flux across the monolayer of control and Bsep-expressing cells was symmetrical. Basal-to-apical transport of taurocholate across Ntcp/Bsep-coexpressing monolayers was significantly higher than that across monolayers expressing only Ntcp. Kinetic analysis of this vectorial transport of taurocholate gave an apparent K(m) value of 13.9 +/- 4.7 microM for cells expressing Ntcp alone, which is comparable with 22.2 +/- 4.5 microM for cells expressing both Ntcp and Bsep and V(max) values of 15.8 +/- 4.2 and 60.8 +/- 9.0 pmol.min(-1).mg protein(-1) for Ntcp alone and Ntcp and Bsep-coexpressing cells, respectively. Transcellular transport of cholate, glycocholate, taurochenodeoxycholate, chenodeoxycholate, glycochenodeoxycholate, tauroursodeoxycholate, ursodeoxycholate, and glycoursodeoxycholate, but not that of lithocholate was also observed across the double transfectant. This double-expressing system can be used as a model to clarify vectorial transport of bile salts across hepatocytes under physiological conditions.

Lysine-specific demethylase 1: an epigenetic regulator of salt-sensitive hypertension.

PubMed

Williams, Jonathan S; Chamarthi, Bindu; Goodarzi, Mark O; Pojoga, Luminita H; Sun, Bei; Garza, Amanda E; Raby, Benjamin A; Adler, Gail K; Hopkins, Paul N; Brown, Nancy J; Jeunemaitre, Xavier; Ferri, Claudio; Fang, Rui; Leonor, Thiago; Cui, Jinrui; Guo, Xiuqing; Taylor, Kent D; Ida Chen, Yii-Der; Xiang, Anny; Raffel, Leslie J; Buchanan, Thomas A; Rotter, Jerome I; Williams, Gordon H; Shi, Yujiang

2012-07-01

Hypertension (HTN) represents a complex heritable disease in which environmental factors may directly affect gene function via epigenetic mechanisms. The aim of this study was to test the hypothesis that dietary salt influences the activity of a histone-modifying enzyme, lysine-specific demethylase 1 (LSD-1), which in turn is associated with salt-sensitivity of blood pressure (BP). Animal and human studies were performed. Salt-sensitivity of LSD-1 expression was assessed in wild-type (WT) and LSD-1 heterozygote knockout (LSD-1(+/-)) mice. Clinical relevance was tested by multivariate associations between single-nuclear polymorphisms (SNPs) in the LSD-1 gene and salt-sensitivity of BP, with control of dietary sodium, in a primary African-American hypertensive cohort and two replication hypertensive cohorts (Caucasian and Mexican-American). LSD-1 expression was modified by dietary salt in WT mice with lower levels associated with liberal salt intake. LSD-1(+/-) mice expressed lower LSD-1 protein levels than WT mice in kidney tissue. Similar to LSD-1(+/-) mice, African-American minor allele carriers of two LSD-1 SNPs displayed greater change in systolic BP (SBP) in response to change from low to liberal salt diet (rs671357, P = 0.01; rs587168, P = 0.005). This association was replicated in the Hispanic (rs587168, P = 0.04) but not the Caucasian cohort. Exploratory analyses demonstrated decreased serum aldosterone concentrations in African-American minor allele carriers similar to findings in the LSD-1(+/-) mice, decreased α-EnaC expression in LSD-1(+/-) mice, and impaired renovascular responsiveness to salt loading in minor allele carriers. The results of this translational research study support a role for LSD-1 in the pathogenesis of salt-sensitive HTN.

Impaired Purinergic Neurotransmission to Mesenteric Arteries in DOCA-salt Hypertensive Rats

PubMed Central

Demel, Stacie L.; Galligan, James J.

2009-01-01

Sympathetic nerves release norepinephrine (NE) and ATP onto mesenteric arteries. In DOCA-salt hypertensive rats, there is increased arterial sympathetic neurotransmission due in part to impaired α2-AR function and impaired prejunctional regulation of NE release. Prejunctional regulation of the purinergic component of sympathetic neuroeffector transmission in hypertension is less well understood. We hypothesized that α2-AR dysfunction alters purinergic neurotransmission to arteries in DOCA-salt hypertensive rats. Mesenteric artery preparations were maintained in vitro and intracellular electrophysiological methods were used to record excitatory junction potentials (EJPs) from smooth muscle cells (SMCs). EJP amplitude was reduced in SMCs from DOCA-salt (4 ± 1 mV) compared to control arteries (9 ± 1 mV; P<0.05). When using short trains of electrical stimulation (0.5 Hz, 5 pulses), the α2-AR antagonist, yohimbine (1 μM), potentiated EJPs in control more than in DOCA-salt arteries (180 ± 35 % vs. 86 ± 7 %; P<0.05). NE (0.1 − 3 μM), the α2-AR agonist UK 14,304 (0.001−0.1 μM), the A1 adenosine receptor agonist CPA (0.3 − 100 μM) and the N-type calcium channel blocker ω–conotoxin (0.0003 − 0.1 μM) decreased EJP amplitude equally well in control and DOCA-salt arteries. Trains of stimuli (10 Hz) depleted ATP stores more completely and the latency to EJP recovery was longer in DOCA-salt compared to control arteries. These data indicate that there is reduced purinergic input to mesenteric arteries of DOCA-salt rats. This is not due to increased inhibition of ATP release via prejunctional α2-ARs or adenosine receptors, but rather a decrease in ATP bioavailability in sympathetic nerves. These data highlight the potential importance of altered neural regulation of resistance arteries as a therapeutic target for drug treatment of hypertension. PMID:18606906

Oral administration of Lentinus edodes β-glucans ameliorates DSS-induced ulcerative colitis in mice via MAPK-Elk-1 and MAPK-PPARγ pathways.

PubMed

Shi, Limin; Lin, Qinlu; Yang, Tao; Nie, Ying; Li, Xinhua; Liu, Bo; Shen, Junjun; Liang, Ying; Tang, Yiping; Luo, Feijun

2016-11-09

To evaluate the anti-inflammatory effect of β-glucans from Lentinus edodes, and its molecular mechanism, the dextran sulfate sodium salt (DSS) induced colitis model of mice and the LPS-stimulated RAW264.7 cell inflammation model were used in this study. 40 ICR male mice were randomly divided into 4 groups: Control, DSS (DSS treated only), DSS + low-βGs (500 mg kg -1 d -1 ) and DSS + high-βGs (1000 mg kg -1 d -1 ). The body weight of the mice with Lentinus edodes β-glucan supplementation increased significantly compared to the DSS group and the disease activity index (DAI) was improved in both βG-treated groups. Compared with the DSS group, histopathological analysis showed that the infiltration of inflammatory cells of both βG-treated groups decreased significantly in colonic tissues. Furthermore, oral administration of β-glucans decreases the concentration of malondialdehyde (MDA) and myeloperoxidase (MPO) and inhibits the expression of iNOS and several inflammatory factors: TNF-α, IL-1β and IL-6 as well as nitric oxide (NO) of the colonic tissues. The mitogen-activated protein kinase (MAPK) pathway is closely related to the expression of pro-inflammatory factors. In the DSS-induced colitis model and the LPS-stimulated RAW264.7 cell model, βGs inhibited the expression of pro-inflammatory factors and blocked the phosphorylation of JNK/ERK1/2 and p38; βGs also suppress the phosphorylation of Elk-1 at Ser84 and the phosphorylation of PPARγ at Ser112. Altogether, these results suggest that Lentinus edodes βGs could inhibit the DSS-induced ulcerative colitis and decrease inflammatory factor expressions. The molecular mechanism may be involved in suppressing MAPK signaling and inactivation of Elk-1 and activation of PPARγ.

Resistant starch modulates in vivo colonic butyrate uptake and its oxidation in rats with dextran sulfate sodium-induced colitis.

PubMed

Moreau, Noëlle M; Champ, Martine M; Goupry, Stéphane M; Le Bizec, Bruno J; Krempf, Michel; Nguyen, Patrick G; Dumon, Henri J; Martin, Lucile J

2004-03-01

We previously demonstrated improvements of colonic lesions due to dextran sulfate sodium (DSS) in rats after 7 d of supplementation with resistant starch (RS) type 3, a substrate yielding high levels of butyrate (C(4)), a colonic cell fuel source. In the present study, we hypothesized that if inflammation is related to decreased C(4) utilization by the colonic mucosa, RS supplementation should restore C(4) use simultaneously with an increase in the amount of C(4) present in the digestive tract. Hence, we compared, in vivo, the cecocolonic uptake of C(4) and its oxidation into CO(2) and ketone bodies in control and DSS-treated rats fed a fiber-free basal diet (BD) or a RS-supplemented diet. Sprague-Dawley rats (n = 60) were used. DSS treatment was performed to induce acute colitis and then to maintain chronic colitis. After cecal infusion of [1-(13)C]-C(4) (20 micro mol in 1 h), concentrations and (13)C-enrichment of C(4), ketone bodies, and CO(2) were quantified in the abdominal aorta and portal vein. Portal blood flow was recorded. During acute colitis, (13)C(4) uptake and (13)CO(2) production were lower in DSS rats than in controls. During chronic colitis, DSS rats did not differ from controls. After 7 d of chronic colitis, RS-DSS rats exhibited the same C(4) uptake as BD-DSS rats in spite of higher C(4) cecocolonic disposal. After 14 d, C(4) uptake was higher in RS-DSS than in BD-DSS rats. Thus, the increased utilization of C(4) by the mucosa is subsequent to evidence of healing and appears to be a consequence rather than a cause of this RS healing effect.

Salt and nitric oxide synthase inhibition-induced hypertension: kidney dysfunction and brain anti-oxidant capacity.

PubMed

Oktar, Süleyman; Ilhan, Selçuk; Meydan, Sedat; Aydin, Mehmet; Yönden, Zafer; Gökçe, Ahmet

2010-01-01

The specific aim of this study was to examine the effects of salt-loading on kidney function and brain antioxidant capacity. Wistar rats were divided into four groups: Control rats were given normal drinking water and no drug treatment for 2 weeks. LNNA group: rats were given normal drinking water and the nitric oxide (NO) inhibitor NG-nitro-L-arginine (L-NNA), 3 mg/kg/day. LNNA + Salt group: rats were given drinking water containing salt 2% and 3 mg/kg L-NNA. Salt group: rats were given drinking water containing salt 2% and no drug treatment. Basal blood pressure and the levels of serum BUN, creatinine, uric acid, cortisol, electrolyte, serum antioxidant capacity, and oxidative stress were measured. NO, superoxide dismutase (SOD), and catalase (CAT) levels were measured in the hypothalamus, brainstem, and cerebellum. Salt overload increased the blood pressure of the LNNA + Salt group. Salt-loading enhanced BUN, creatinine, sodium retention. High salt produced an increase in uric acid levels and a decrease in cortisol levels in serum. Additionally, the oxidative stress index in serum increased in the LNNA + Salt group. Salt-loading enhanced brain NO levels, but not SOD and CAT activity. L-NNA increased brain SOD activity, but not CAT and NO levels. In conclusion, salt-loading causes hypertension, kidney dysfunction, and enhances oxidative stress in salt-sensitive rats.

Vascular structure and oxidative stress in salt-loaded spontaneously hypertensive rats: effects of losartan and atenolol.

PubMed

de Cavanagh, Elena M V; Ferder, León F; Ferder, Marcelo D; Stella, Inés Y; Toblli, Jorge E; Inserra, Felipe

2010-12-01

Renin-angiotensin system (RAS) modulation by high dietary sodium may contribute to salt-induced hypertension, oxidative stress, and target organ damage. We investigated whether angiotensin II (Ang-II) type 1 (AT1)-receptor blockade (losartan) could protect the aorta and renal arteries from combined hypertension- and high dietary salt-related oxidative stress. Spontaneously hypertensive rats (3-month-old, n = 10/group) received tap water (SHR), water containing 1.5% NaCl (SHR+S), 1.5% NaCl and 30 mg losartan/kg/day (SHR+S+L), or 50 mg atenolol/kg/day (SHR+S+A). Atenolol was used for comparison. Ten Wistar-Kyoto rats (WKY) were controls. Systolic blood pressure (SBP) was determined by tail plethysmography. After 5 months of treatment, vascular remodeling and oxidative stress (superoxide production and NAD(P)H-oxidase activity (chemiluminescence), malondialdehyde (MDA) content (high-performance liquid chromatography), endothelial nitric oxide synthase (eNOS) activity [(14)C-arginine to (14)C citrulline], CuZn-SOD activity (spectrophotometry)) were studied. In SHR, salt-loading significantly aggravated hypertension, urinary protein excretion, intraparenchymal renal artery (IPRArt) perivascular fibrosis, aortic and renal artery oxidative stress, and induced endothelial cell loss in IPRArts. In salt-loaded SHR, 5-month losartan and atenolol treatments similarly reduced SBP, but only losartan significantly prevented (i) urinary protein excretion increase, (ii) or attenuated hypertension-related vascular remodeling, (iii) aortic MDA accumulation, (iv) renal artery eNOS activity lowering, and (v) aortic and renal artery superoxide dismutase (SOD) activity reduction. In SHR+S, the contributions to aortic superoxide production were as follows: uncoupled eNOS > xanthine oxidase (XO) > NAD(P)H oxidase. In this salt-sensitive genetic hypertension model, losartan protects from hypertension- and high dietary salt-related vascular oxidative stress, exceeding the benefits of BP

SENSITIVE TO FREEZING2 Aids in Resilience to Salt and Drought in Freezing-Sensitive Tomato

DOE PAGES

Wang, Kun; Hersh, Hope Lynn; Benning, Christoph

2016-09-06

SENSITIVE TO FREEZING2 (SFR2) is crucial for protecting chloroplast membranes following freezing in Arabidopsis (Arabidopsis thaliana). It has been shown that SFR2 homologs are present in all land plants, including freezing-sensitive species, raising the question of SFR2 function beyond freezing tolerance. Similar to freezing, salt and drought can cause dehydration. Thus, it is hypothesized that in freezing-sensitive plants SFR2 may play roles in their resilience to salt or drought. To test this hypothesis, SlSFR2 RNAi lines were generated in the cold/freezing-sensitive species tomato (Solanum lycopersicum [M82 cv]). Hypersensitivity to salt and drought of SlSFR2-RNAi lines was observed. Higher tolerance ofmore » wild-type tomatoes was correlated with the production of trigalactosyldiacylglycerol, a product of SFR2 activity. Tomato SFR2 in vitro activity is Mg 2+-dependent and its optimal pH is 7.5, similar to that of Arabidopsis SFR2, but the specific activity of tomato SFR2 in vitro is almost double that of Arabidopsis SFR2. When salt and drought stress were applied to Arabidopsis, no conditions could be identified at which SFR2 was induced prior to irreversibly impacting plant growth, suggesting that SFR2 protects Arabidopsis primarily against freezing. Discovery of tomato SFR2 function in drought and salt resilience provides further insights into general membrane lipid remodeling-based stress tolerance mechanisms and together with protection against freezing in freezing-resistant plants such as Arabidopsis, it adds lipid remodeling as a possible target for the engineering of abiotic stress-resilient crops.« less

SENSITIVE TO FREEZING2 Aids in Resilience to Salt and Drought in Freezing-Sensitive Tomato

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

Wang, Kun; Hersh, Hope Lynn; Benning, Christoph

SENSITIVE TO FREEZING2 (SFR2) is crucial for protecting chloroplast membranes following freezing in Arabidopsis (Arabidopsis thaliana). It has been shown that SFR2 homologs are present in all land plants, including freezing-sensitive species, raising the question of SFR2 function beyond freezing tolerance. Similar to freezing, salt and drought can cause dehydration. Thus, it is hypothesized that in freezing-sensitive plants SFR2 may play roles in their resilience to salt or drought. To test this hypothesis, SlSFR2 RNAi lines were generated in the cold/freezing-sensitive species tomato (Solanum lycopersicum [M82 cv]). Hypersensitivity to salt and drought of SlSFR2-RNAi lines was observed. Higher tolerance ofmore » wild-type tomatoes was correlated with the production of trigalactosyldiacylglycerol, a product of SFR2 activity. Tomato SFR2 in vitro activity is Mg 2+-dependent and its optimal pH is 7.5, similar to that of Arabidopsis SFR2, but the specific activity of tomato SFR2 in vitro is almost double that of Arabidopsis SFR2. When salt and drought stress were applied to Arabidopsis, no conditions could be identified at which SFR2 was induced prior to irreversibly impacting plant growth, suggesting that SFR2 protects Arabidopsis primarily against freezing. Discovery of tomato SFR2 function in drought and salt resilience provides further insights into general membrane lipid remodeling-based stress tolerance mechanisms and together with protection against freezing in freezing-resistant plants such as Arabidopsis, it adds lipid remodeling as a possible target for the engineering of abiotic stress-resilient crops.« less

Grape seed proanthocyanidins prevent DOCA-salt hypertension-induced renal injury and its mechanisms in rats.

PubMed

Lan, Chao-Zong; Ding, Ling; Su, Yi-Lin; Guo, Kun; Wang, Li; Kan, Hong-Wei; Ou, Yu-Rong; Gao, Shan

2015-07-01

Renal dysfunction is one of the major effects of DOCA (deoxycorticosterone acetate)-salt hypertension and there is an increasing amount of evidence that oxidative stress damages the function of the kidney. Grape seed proanthocyanidins (GSPE) have been reported to be potent anti-oxidants and free radical scavengers. The present study sought to investigate the ability of GSPE to prevent renal injury in DOCA-salt hypertensive rats and to explore the molecular mechanisms underlying its protective effects. A total of 54 Sprague Dawley (SD) rats were randomly divided into 7 groups: Sham group (n = 7), UnX-sham group (n = 8), DOCA-salt group (n = 8), GSPE150 group (150 mg kg(-1), n = 7), GSPE240 group (240 mg kg(-1), n = 8), GSPE384 group (384 mg kg(-1), n = 8) and ALM (amlodipine besylate tablets) group (5 mg kg(-1), n = 8), and treated for 4 weeks. Compared to sham group rats, renal injury was observed in DOCA-salt hypertensive group rats as the urine protein, KW/BW (kidney weight/body weight), degree of renal fibrosis, renal MDA (malondialdehyde) and Hyp (hydroxyproline) contents significantly increased (P < 0.01). Moreover, SOD (Superoxide Dismutase) activities decreased in the model group (P < 0.01). In contrast, DOCA-salt hypertensive rats treated with different dose of GSPE or ALM showed a significant improvement of renal injury with decreased urine protein, KW/BW, degree of renal fibrosis, renal total MDA and Hyp contents compared to the untreated group. In addition, SOD activities increased in the treatment group. Since the experimental modeling time was short, kidney damage occurs to a lesser extent. BUN (Blood Urea Nitrogen), Scr (Serum Creatinine) and UA (Uric Acid) contents did not appear significantly changed in all groups. Finally, the activation of JNK and p38 kinases in the kidney was suppressed in rats treated with GSPEs or ALM compared to the untreated group, suggesting that the inhibition of these kinase pathways by GSPE contributes to the improvement

32 CFR 321.14 - DSS implementation policies.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.14 DSS implementation policies. (a) General... matters of particular concern to the Defense Security Service. (b) Privacy Act rules application. Any... 32 National Defense 2 2014-07-01 2014-07-01 false DSS implementation policies. 321.14 Section 321...

32 CFR 321.14 - DSS implementation policies.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.14 DSS implementation policies. (a) General... matters of particular concern to the Defense Security Service. (b) Privacy Act rules application. Any... 32 National Defense 2 2013-07-01 2013-07-01 false DSS implementation policies. 321.14 Section 321...

32 CFR 321.14 - DSS implementation policies.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.14 DSS implementation policies. (a) General... matters of particular concern to the Defense Security Service. (b) Privacy Act rules application. Any... 32 National Defense 2 2012-07-01 2012-07-01 false DSS implementation policies. 321.14 Section 321...

A High Salt Diet Inhibits Obesity and Delays Puberty in the Female Rat

PubMed Central

Pitynski-Miller, Dori; Ross, Micah; Schmill, Margaret; Schambow, Rachel; Fuller, Teresa; Flynn, Francis W.; Skinner, Donal C.

2017-01-01

Background/Objectives Processed foods are considered major contributors to the worldwide obesity epidemic. In addition to high sugar and fat contents, processed foods contain large amounts of salt. Due to correlations with rising adiposity, salt has recently been proposed to be obesogenic. This study investigated three hypotheses: i) high salt contributes to weight gain and adiposity in juvenile female rats, ii) puberty onset would be altered because salt is known to affect neuronal systems involved in activating the reproductive system, and iii) enhanced adiposity will act synergistically with salt to drive early puberty onset. Design Female weanling rats (post-natal day 21, n=105) were fed a low fat/low salt diet, low fat/high salt diet, high fat/low salt diet, or a high salt/high fat diet for 24 days. Metabolic measures, including weight gain, food intake, fecal output, activity, and temperature were recorded in subsets of animals. Results Body weight, retroperitoneal and perirenal fat pad weight, and adipocyte size were all lower in animals fed high fat/high salt compared to animals fed high fat alone. Leptin levels were reduced in high fat/high salt fed animals compared to high fat/low salt fed animals. Daily calorie intake was higher initially but declined with adjusted food intake and was not different among groups after 5 days. Osmolality and corticosterone were not different among groups. Fecal analysis showed excess fat excretion and a decreased digestive efficiency in animals fed high fat/low salt but not in animals fed high fat/high salt. Although respiratory exchange ratio was reduced by high dietary fat or salt, aerobic resting metabolic rate was not affected by diet. High salt delayed puberty onset, regardless of dietary fat content. Conclusions Salt delays puberty and prevents the obesogenic effect of a high fat diet. The reduced weight gain evident in high salt fed animals is not due to differences in food intake or digestive efficiency. PMID

Atmospheric refraction correction for Ka-band blind pointing on the DSS-13 beam waveguide antenna

NASA Technical Reports Server (NTRS)

Perez-Borroto, I. M.; Alvarez, L. S.

1992-01-01

An analysis of the atmospheric refraction corrections at the DSS-13 34-m diameter beam waveguide (BWG) antenna for the period Jul. - Dec. 1990 is presented. The current Deep Space Network (DSN) atmospheric refraction model and its sensitivity with respect to sensor accuracy are reviewed. Refraction corrections based on actual atmospheric parameters are compared with the DSS-13 station default corrections for the six-month period. Average blind-pointing improvement during the worst month would have amounted to 5 mdeg at 10 deg elevation using actual surface weather values. This would have resulted in an average gain improvement of 1.1 dB.

Deep Space Station (DSS-13) automation demonstration

NASA Technical Reports Server (NTRS)

Remer, D. S.; Lorden, G.

1980-01-01

The data base collected during a six month demonstration of an automated Deep Space Station (DSS 13) run unattended and remotely controlled is summarized. During this period, DSS 13 received spacecraft telemetry data from Voyager, Pioneers 10 and 11, and Helios projects. Corrective and preventive maintenance are reported by subsystem including the traditional subsystems and those subsystems added for the automation demonstration. Operations and maintenance data for a comparable manned Deep Space Station (DSS 11) are also presented for comparison. The data suggests that unattended operations may reduce maintenance manhours in addition to reducing operator manhours. Corrective maintenance for the unmanned station was about one third of the manned station, and preventive maintenance was about one half.

Dietary protocatechuic acid ameliorates dextran sulphate sodium-induced ulcerative colitis and hepatotoxicity in rats.

PubMed

Farombi, Ebenezer O; Adedara, Isaac A; Awoyemi, Omolola V; Njoku, Chinonye R; Micah, Gabriel O; Esogwa, Cynthia U; Owumi, Solomon E; Olopade, James O

2016-02-01

The present study investigated the antioxidant and anti-inflammatory effects of dietary protocatechuic acid (PCA), a simple hydrophilic phenolic compound commonly found in many edible vegetables, on dextran sulphate sodium (DSS)-induced ulcerative colitis and its associated hepatotoxicity in rats. PCA was administered orally at 10 mg kg(-1) to dextran sulphate sodium exposed rats for five days. The result revealed that administration of PCA significantly (p < 0.05) prevented the incidence of diarrhea and bleeding, the decrease in the body weight gain, shortening of colon length and the increase in colon mass index in DSS-treated rats. Furthermore, PCA prevented the increase in the plasma levels of pro-inflammatory cytokines, markers of liver toxicity and markedly suppressed the DSS-mediated elevation in colonic nitric oxide concentration and myeloperoxidase activity in the treated rats. Administration of PCA significantly protected against colonic and hepatic oxidative damage by increasing the antioxidant status and concomitantly decreased hydrogen peroxide and lipid peroxidation levels in the DSS-treated rats. Moreover, histological examinations confirmed PCA chemoprotection against colon and liver damage. Immunohistochemical analysis showed that PCA significantly inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in the colon of DSS-treated rats. In conclusion, the effective chemoprotective role of PCA in colitis and the associated hepatotoxicity is related to its intrinsic anti-inflammatory and anti-oxidative properties.

Matlab-Excel Interface for OpenDSS

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

The software allows users of the OpenDSS grid modeling software to access their load flow models using a GUI interface developed in MATLAB. The circuit definitions are entered into a Microsoft Excel spreadsheet which makes circuit creation and editing a much simpler process than the basic text-based editors used in the native OpenDSS interface. Plot tools have been developed which can be accessed through a MATLAB GUI once the desired parameters have been simulated.

Acute and subacute oral toxicity of periodate salts in rats.

PubMed

Lent, Emily May; Crouse, Lee C B; Eck, William S

2017-02-01

Periodate salts are being developed as potential replacements for perchlorate due to potential health hazards associated with exposure to perchlorate. The aim of this study was to investigate acute and subacute effects of periodate salts in rats. Acute oral toxicity of potassium and sodium periodate was determined using the Sequential Stage-Wise Probit method. The LD 50 for potassium periodate was 732 (95% CI = 539-838, slope = 13.4) and 685 mg/kg (95% CI = 580-809, slope = 10.6) for females and males, respectively. The LD 50 for sodium periodate was 318 (95% CI = 292-347, slope = 24.3) and 741 mg/kg (95% CI = 704-779, slope = 31.2) for females and males, respectively. In the subacute study, rats were administered sodium periodate at five doses (1/16 LD 50 up to LD 50 ) or distilled water for 14-days via oral gavage. Female rats in the 318 mg/kg-day group and male rats in the 185, 370, and 741 mg/kg-day groups exhibited moribundity, kidney toxicity, uremia, and a stress response. BMDL 10 s of 17.2 and 33.7 mg/kg-day were derived for females and males, respectively. Comparison with the NOAEL for perchlorate-induced thyroid toxicity in rats (0.009 mg/kg-day) suggests sodium periodate is less toxic than perchlorate on a subacute basis. Copyright © 2016. Published by Elsevier Inc.

A Participants' DSS for a Management Game with a DSS Generator.

ERIC Educational Resources Information Center

Yeo, Gee Kin; Nah, Fui Hoon

1992-01-01

Describes the design of a decision support system (DSS) for a management game called MAGNUS (Management Game for National University of Singapore). Built-in models for performance analysis and decision making are explained; database query and model building are described; and future work is discussed. (11 references) (LRW)

Economic evaluation of DSS 13 unattended operations demonstration

NASA Technical Reports Server (NTRS)

Remer, D. S.; Eisenberger, I.; Lorden, G.

1978-01-01

The goals and data collection requirements to be used for the economic and performance evaluation indexes and life cycle cost parameters for the upcoming operations demonstration of an automated Deep Space Station (DSS) run unattended and controlled remotely from JPL are presented. These evaluation indexes compare the remote operation of telemetry at DSS 13 with the cost and performance of a comparable manned operation at DSS 11. A description is presented of the data that needs to be collected, how the data will be analyzed, and what can and cannot be learned from this operations demonstration.

SENSITIVE TO FREEZING2 Aids in Resilience to Salt and Drought in Freezing-Sensitive Tomato1[OPEN

PubMed Central

Hersh, Hope Lynn

2016-01-01

SENSITIVE TO FREEZING2 (SFR2) is crucial for protecting chloroplast membranes following freezing in Arabidopsis (Arabidopsis thaliana). It has been shown that SFR2 homologs are present in all land plants, including freezing-sensitive species, raising the question of SFR2 function beyond freezing tolerance. Similar to freezing, salt and drought can cause dehydration. Thus, it is hypothesized that in freezing-sensitive plants SFR2 may play roles in their resilience to salt or drought. To test this hypothesis, SlSFR2 RNAi lines were generated in the cold/freezing-sensitive species tomato (Solanum lycopersicum [M82 cv]). Hypersensitivity to salt and drought of SlSFR2-RNAi lines was observed. Higher tolerance of wild-type tomatoes was correlated with the production of trigalactosyldiacylglycerol, a product of SFR2 activity. Tomato SFR2 in vitro activity is Mg2+-dependent and its optimal pH is 7.5, similar to that of Arabidopsis SFR2, but the specific activity of tomato SFR2 in vitro is almost double that of Arabidopsis SFR2. When salt and drought stress were applied to Arabidopsis, no conditions could be identified at which SFR2 was induced prior to irreversibly impacting plant growth, suggesting that SFR2 protects Arabidopsis primarily against freezing. Discovery of tomato SFR2 function in drought and salt resilience provides further insights into general membrane lipid remodeling-based stress tolerance mechanisms and together with protection against freezing in freezing-resistant plants such as Arabidopsis, it adds lipid remodeling as a possible target for the engineering of abiotic stress-resilient crops. PMID:27600812

Acute elevations in salt intake and reduced renal mass hypertension compromise arteriolar dilation in rat cremaster muscle.

PubMed

Frisbee, J C; Lombard, J H

1999-05-01

Alterations in arteriolar reactivity to dilator agonists were assessed in the skeletal muscle microcirculation of normotensive male Sprague-Dawley rats fed either high- (4% NaCl; HS) or low- (0. 4% NaCl; LS) salt diets and in reduced renal mass hypertensive rats (RRM-HT) on a high-salt diet for 3 days. An in situ cremaster muscle preparation was superfused with physiological salt solution, transilluminated, and viewed via television microscopy. A videomicrometer was used to measure changes in diameter of distal arterioles in response to increasing concentrations of acetylcholine (ACH), iloprost (ILO), cholera toxin (CT), forskolin (FOR), and sodium nitroprusside (SNP). Arteriolar dilation in response to ACH, ILO, and CT was significantly reduced in both HS and RRM-HT rats, while responses to FOR and SNP were decreased in RRM-HT rats only. The maximum dilation of the arterioles (determined during superfusion of the muscle with Ca2+-free solution containing 10(-4) M adenosine) was similar in the normotensive control animals on LS and HS diets, but was reduced in the RRM-HT rats, suggesting that early anatomic remodeling of the vessel wall may be occurring with RRM-HT. We conclude that arteriolar reactivity to endothelium-dependent and -independent vasodilator agonists is impaired as early as 3 days after the development of RRM hypertension or commencement of a high-salt diet in normotensive rats. Structural remodeling of the arteriolar wall, although becoming evident in the hypertensive rats, takes longer to develop than the impaired vasodilator reactivity. Copyright 1999 Academic Press.

Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse

PubMed Central

Zhang, Jie; He, Kan; Cai, Lining; Chen, Yu-Chuan; Yang, Yifan; Shi, Qin; Woolf, Thomas F.; Ge, Weigong; Guo, Lei; Borlak, Jürgen; Tong, Weida

2018-01-01

Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time– and bile-acid-concentration–dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values <50 μM), but only about 20% of the non-sDILI drugs showed this strength of inhibition in primary human hepatocytes and these drugs are associated only with cholestatic and mixed hepatocellular cholestatic (mixed) injuries. The sDILI drugs, which did not show substantial inhibition of bile salt transport activity, are likely to be associated with immune-mediated liver injury. Twenty-four drugs were also tested in monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug-derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune

Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse.

PubMed

Zhang, Jie; He, Kan; Cai, Lining; Chen, Yu-Chuan; Yang, Yifan; Shi, Qin; Woolf, Thomas F; Ge, Weigong; Guo, Lei; Borlak, Jürgen; Tong, Weida

2016-08-05

Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time‒ and bile-acid-concentration‒dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values <50 μM), but only about 20% of the non-sDILI drugs showed this strength of inhibition in primary human hepatocytes and these drugs are associated only with cholestatic and mixed hepatocellular cholestatic (mixed) injuries. The sDILI drugs, which did not show substantial inhibition of bile salt transport activity, are likely to be associated with immune-mediated liver injury. Twenty-four drugs were also tested in monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug-derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune

The area postrema does not modulate the long-term salt sensitivity of arterial pressure.

PubMed

Collister, J P; Osborn, J W

1998-10-01

The hindbrain circumventricular organ, the area postrema (AP), receives multiple signals linked to body fluid homeostasis. In addition to baroreceptor input, AP cells contain receptors for ANG II, vasopressin, and atrial natriuretic peptide. Hence, it has been proposed that the AP is critical in long-term adjustments in sympathetic outflow in response to changes in dietary NaCl. The present study was designed to test the hypothesis that long-term control of arterial pressure over a range of dietary NaCl requires an intact AP. Male Sprague-Dawley rats were randomly selected for lesion of the AP (APx) or sham lesion. Three months later, rats were instrumented with radiotelemetry transmitters for continuous monitoring of mean arterial pressure (MAP) and heart rate and were placed in individual metabolic cages. Rats were given 1 wk postoperative recovery. The dietary salt protocol consisted of a 7-day period of 1.0% NaCl (control), 14 days of 4.0% NaCl (high), 7 days of 1.0% NaCl, and finally 14 days of 0.1% NaCl (low). The results are reported as the average arterial pressure observed on the last day of the given dietary salt period: APx (n = 7) 114 +/- 2 (1.0%), 110 +/- 3 (4.0%), 110 +/- 3 (1.0%), and 114 +/- 4 (0.1%) mmHg; sham (n = 6) 115 +/- 2 (1.0%), 114 +/- 3 (4.0%), 111 +/- 3 (1. 0%), and 113 +/- 2 (0.1%) mmHg. Neither group of rats demonstrated significant changes in MAP throughout the entire dietary salt protocol. Furthermore, no significant differences in MAP were detected between groups throughout the protocol. All lesions were histologically verified. These results suggest that the area postrema plays no role in long-term control of arterial pressure during chronic changes in dietary salt.

Genetic Decreases in Atrial Natriuretic Peptide and Salt-Sensitive Hypertension

NASA Astrophysics Data System (ADS)

John, Simon W. M.; Krege, John H.; Oliver, Paula M.; Hagaman, John R.; Hodgin, Jeffrey B.; Pang, Stephen C.; Flynn, T. Geoffrey; Smithies, Oliver

1995-02-01

To determine if defects in the atrial natriuretic peptide (ANP) system can cause hypertension, mice were generated with a disruption of the proANP gene. Homozygous mutants had no circulating or atrial ANP, and their blood pressures were elevated by 8 to 23 millimeters of mercury when they were fed standard (0.5 percent sodium chloride) and intermediate (2 percent sodium chloride) salt diets. On standard salt diets, heterozygotes had normal amounts of circulating ANP and normal blood pressures. However, on high (8 percent sodium chloride) salt diets they were hypertensive, with blood pressures elevated by 27 millimeters of mercury. These results demonstrate that genetically reduced production of ANP can lead to salt-sensitive hypertension.

Effect of Genetic Information Regarding Salt-Sensitive Hypertension on the Intent to Maintain a Reduced Salt Diet: Implications for Health Communication in Japan.

PubMed

Miyamoto, Keiko; Iwakuma, Miho; Nakayama, Takeo

2017-03-01

The authors investigated the relationship between the awareness of dietary salt and genetics and the intent to maintain a low-salt diet. In particular, they assessed whether hypothetical genetic information regarding salt-sensitive hypertension motivates the intent to reduce dietary salt for communicating the health benefits of lower salt consumption to citizens. A self-administered questionnaire survey was conducted with 2500 randomly sampled residents aged 30 to 69 years living in Nagahama, Japan. Genetic information regarding higher salt sensitivity increased motivation to reduce salt intake for both those who agreed that genes cause hypertension and those who did not. Less than 50% of those who agreed that genes cause hypertension lost their intention to lower their salt consumption when they found they did not possess the susceptibility gene. Communicating genetic information positively affected motivation to reduce salt intake. The present study clarifies the difficulty in changing the behavioral intent of those who have significantly less incentive to reduce salt intake. Therefore, a multidimensional approach is crucial to reduce salt consumption. ©2016 Wiley Periodicals, Inc.

Forebrain circumventricular organs mediate salt appetite induced by intravenous angiotensin II in rats.

PubMed

Morris, Michael J; Wilson, Wendy L; Starbuck, Elizabeth M; Fitts, Douglas A

2002-09-13

Two circumventricular organs, the subfornical organ (SFO) and organum vasculosum laminae terminalis (OVLT), may mediate salt appetite in response to acute intravenous infusions of angiotensin (ANG) II. Fluid intakes and mean arterial pressures were measured in rats with sham lesions or electrolytic lesions of the SFO or OVLT during an intravenous infusion of 30 ng/min ANG II. Beginning 21 h before the 90-min infusion, the rats were depleted of sodium with furosemide and given a total of 300 mg/kg captopril in 75 ml/kg water in three spaced gavages to block the usual salt appetite and to hydrate the rats. No other food or fluids were available for ingestion. Sham-lesioned rats drank 9.3+/-1.2 ml if 0.3 M NaCl alone was available and drank 8.9+/-1.6 ml of saline and 3.7+/-1.6 ml of water if both were available. Either SFO or OVLT lesions reduced the intakes of saline to <5 ml in both conditions and of water to <1 ml. Mean arterial pressure did not differ among the groups and was maintained above 100 mmHg after the depletion and captopril treatments because of the large doses of water. Thus, a full expression of salt appetite in response to an acute intravenous infusion of ANG II requires the integrity of both the SFO and OVLT. Copyright 2002 Elsevier Science B.V.

Effects of excess salt and fat intake on myocardial function and infarct size in rat.

PubMed

Mozaffari, Mahmood S; Patel, Champa; Ballas, Claudia; Schaffer, Stephen W

2006-03-13

Important risk factors for cardiovascular disease include excess dietary intake of saturated fat and (or) salt. This study tested the hypothesis that excess intakes of saturated fat (e.g., beef tallow) and salt cause greater myocardial cell death following ischemia-reperfusion injury than each risk factor alone. Male rats were divided into four groups: basal fat diet (4.5% as calories; control), high fat diet (40% as calories; FAT), basal fat diet and high salt (1% NaCl solution; SALT) and high fat diet and high salt (FATSALT). The gain in body weight was significantly higher for FAT and FATSALT groups than those of either the control or the SALT group. Five weeks of exposure to the dietary regimens did not significantly affect the coronary flow rate and except for the salt-fed group, had no effect on the rate-pressure-product of the isolated heart perfused in Langendorff mode. Although infarct size was not affected by the high fat diet, it was reduced by the high salt regimen relative to the high fat diet or the control groups. When rats were fed the FAT and SALT combination, the effect of salt feeding on infarct size was not observed. In addition, the FATSALT group displayed a more marked deterioration in contractile function following ischemia-reperfusion injury than the other groups. In conclusion, short-term intake of a high fat diet, which significantly increases body weight, does not worsen ischemia-reperfusion injury although the treatment prevents the reduction of infarct size associated with high salt feeding.

Essential role of Kir5.1 channels in renal salt handling and blood pressure control

PubMed Central

Levchenko, Vladislav; Ilatovskaya, Daria V.; Pavlov, Tengis S.; Pochynyuk, Oleh M.; Jacob, Howard J.; Geurts, Aron M.; Hodges, Matthew R.

2017-01-01

Supplementing diets with high potassium helps reduce hypertension in humans. Inwardly rectifying K+ channels Kir4.1 (Kcnj10) and Kir5.1 (Kcnj16) are highly expressed in the basolateral membrane of distal renal tubules and contribute to Na+ reabsorption and K+ secretion through the direct control of transepithelial voltage. To define the importance of Kir5.1 in blood pressure control under conditions of salt-induced hypertension, we generated a Kcnj16 knockout in Dahl salt-sensitive (SS) rats (SSKcnj16–/–). SSKcnj16–/– rats exhibited hypokalemia and reduced blood pressure, and when fed a high-salt diet (4% NaCl), experienced 100% mortality within a few days triggered by salt wasting and severe hypokalemia. Electrophysiological recordings of basolateral K+ channels in the collecting ducts isolated from SSKcnj16–/– rats revealed activity of only homomeric Kir4.1 channels. Kir4.1 expression was upregulated in SSKcnj16–/– rats, but the protein was predominantly localized in the cytosol in SSKcnj16–/– rats. Benzamil, but not hydrochlorothiazide or furosemide, rescued this phenotype from mortality on a high-salt diet. Supplementation of high-salt diet with increased potassium (2% KCl) prevented mortality in SSKcnj16–/– rats and prevented or mitigated hypertension in SSKcnj16–/– or control SS rats, respectively. Our results demonstrate that Kir5.1 channels are key regulators of renal salt handling in SS hypertension. PMID:28931751

Preliminary maintenance experience for DSS 13 unattended operations demonstration. [Deep Space Network

NASA Technical Reports Server (NTRS)

Remer, D. S.; Lorden, G.

1979-01-01

The maintenance data base collected for 15 weeks of recent unattended and automated operation of DSS 13 is summarized. During this period, DSS 13 was receiving spacecraft telemetry while being controlled remotely from JPL in Pasadena. Corrective and preventive maintenance manhours are reported by subsystem for DSS 13 including the equipment added for the automation demonstration. The corrective and preventive maintenance weekly manhours at DSS 13 averaged 22 and 40, respectively. The antenna hydraulic and electronic systems accounted for about half of the preventive and corrective maintenance manhours for a comparable attended DSN station, DSS 11.

Integrating economy, ecology and uncertainty in an oil-spill DSS: The Prestige accident in Spain, 2002

NASA Astrophysics Data System (ADS)

Wirtz, Kai W.; Liu, Xin

2006-12-01

Major accidental oil spills still affect sensitive marine areas and shorelines around the world, constituting a challenge for operational as well as strategic contingency management. As a rationale basis for addressing both issues we here propose a Decision Support System (DSS) consisting of a combination of modelling and evaluation methods which in particular assesses various impacts on habitats and local economies. By integrating the state-of-the-art oil spill contingency simulation system OSCAR with wind and current forecasts, environmental GIS data and multi-criteria analysis techniques, the DSS is able to rank different response actions to a chemical or oil spill. In this study, the usefulness of the approach is tested by hindcasting the Prestige accident off the coast of Spain in 2002. In particular, the short- to mid-term economic and ecological consequences of different mitigation measures are estimated. We identified clearly one worst option matching the actual decision taken by the responsible parties and one or two almost equally well performing routes. Two procedures of including uncertainty at various stages of the DSS are tested. The first method averages ensembles of outcomes between each modelling/evaluation stage, while the second one preserves the entire degree of freedom till the final ranking procedure. Results in the Prestige case turned out to be rather insensitive against both ways to account for uncertainties. The robustness as well as clarity of the DSS has the potential to enhance the efficiency of decision making even in politically sensitive situations. Limitations as well as ongoing improvements of the system are highlighted, in particular emphasizing linkages to environmental economics.

Biliary excretion of pravastatin and taurocholate in rats with bile salt export pump (Bsep) impairment.

PubMed

Cheng, Yaofeng; Freeden, Chris; Zhang, Yueping; Abraham, Pamela; Shen, Hong; Wescott, Debra; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

2016-07-01

The bile salt export pump (BSEP) is expressed on the canalicular membrane of hepatocytes regulating liver bile salt excretion, and impairment of BSEP function may lead to cholestasis in humans. This study explored drug biliary excretion, as well as serum chemistry, individual bile acid concentrations and liver transporter expressions, in the SAGE Bsep knockout (KO) rat model. It was observed that the Bsep protein in KO rats was decreased to 15% of that in the wild type (WT), as quantified using LC-MS/MS. While the levels of Ntcp and Mrp2 were not significantly altered, Mrp3 expression increased and Oatp1a1 decreased in KO animals. Compared with the WT rats, the KO rats had similar serum chemistry and showed normal liver transaminases. Although the total plasma bile salts and bile flow were not significantly changed in Bsep KO rats, individual bile acids in plasma and liver demonstrated variable changes, indicating the impact of Bsep KO. Following an intravenous dose of deuterium labeled taurocholic acid (D4-TCA, 2 mg/kg), the D4-TCA plasma exposure was higher and bile excretion was delayed by approximately 0.5 h in the KO rats. No differences were observed for the pravastatin plasma concentration-time profile or the biliary excretion after intravenous administration (1 mg/kg). Collectively, the results revealed that these rats have significantly lower Bsep expression, therefore affecting the biliary excretion of endogenous bile acids and Bsep substrates. However, these rats are able to maintain a relatively normal liver function through the remaining Bsep protein and via the regulation of other transporters. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis.

PubMed

Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting; Larsson, Erik; Wåhlin, Nils; Jensen, Boye L; G Persson, A Erik; Carlström, Mattias

2016-01-01

Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P < 0.05) and displayed increased urine production and lower urine osmolality. The blood pressure change in response to salt loading (salt sensitivity) was more pronounced in the PUUO group compared with the control group (15 ± 2 vs. 5 ± 1 mmHg, P < 0.05). Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P < 0.05) and normalized the renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates

Selective aldosterone blockade prevents angiotensin II/salt-induced vascular inflammation in the rat heart.

PubMed

Rocha, Ricardo; Martin-Berger, Cynthia L; Yang, Pochang; Scherrer, Rachel; Delyani, John; McMahon, Ellen

2002-12-01

We studied the role of aldosterone (aldo) in myocardial injury in a model of angiotensin (Ang) II-hypertension. Wistar rats were given 1% NaCl (salt) to drink and randomized into one of the following groups (n = 10; treatment, 21 d): 1) vehicle control (VEH); 2) Ang II infusion (25 ng/min, sc); 3) Ang II infusion plus the selective aldo blocker, eplerenone (epl, 100 mg/kg.d, orally); 4) Ang II infusion in adrenalectomized (ADX) rats; and 5) Ang II infusion in ADX rats with aldo treatment (20 micro g/kg.d, sc). ADX rats received also dexamethasone (12 micro g/kg.d, sc). Systolic blood pressure increased with time in all treatment groups except the VEH group (VEH, 136 +/- 6; Ang II/NaCl, 203 +/- 12; Ang II/NaCl/epl, 196 +/- 10; Ang II/NaCl/ADX, 181 +/- 7; Ang II/NaCl/ADX/aldo, 236 +/- 8 mm Hg). Despite similar levels of hypertension, epl and ADX attenuated the increase in heart weight/body weight induced by Ang II. Histological examination of the hearts evidenced myocardial and vascular injury in the Ang II/salt (7 of 10 hearts with damage, P < 0.05 vs. VEH) and Ang II/salt/ADX/aldo groups (10 of 10 hearts with damage, P < 0.05). Injury included arterial fibrinoid necrosis, perivascular inflammation (primarily macrophages), and focal infarctions. Vascular lesions were associated with expression of the inflammatory mediators cyclooxygenase 2 (COX-2) and osteopontin in the media of coronary arteries. Myocardial injury, COX-2, and osteopontin expression were markedly attenuated by epl treatment (1 of 10 hearts with damage, P < 0.05 vs. Ang II/salt) and adrenalectomy (2 of 10 hearts with damage, P < 0.05 vs. Ang II/salt). Our data indicate that aldo plays a major role in Ang II-induced vascular inflammation in the heart and implicate COX-2 and osteopontin as potential mediators of the damage.

Lithium evokes a more pronounced natriuresis when administered orally than when given intravenously to salt-depleted rats.

PubMed

Mu, J; Johansson, M; Hansson, G C; Lundgren, O

1999-07-01

The effects on renal sodium excretion of giving lithium chloride (LiCl; 0.75 mmol per kg body mass) by gavage or intravenously were investigated. The experiments were carried out on Wistar-Kyoto (WKY) or spontaneously hypertensive (SHR) rats in metabolic cages. The rats had been on a low-salt diet for 4 days. Urine excretion of water, sodium and potassium was followed before and for 24 h after giving LiCl. An oral dose of LiCl evoked a more pronounced renal sodium excretion in either strain of rat as compared to that following intravenous administration, in agreement with previous observations of the effects of giving sodium chloride. Choline chloride (1.5 mmol per kg body mass) given by gavage to WKY rats or SHR evoked no change in the renal excretion of sodium. Based on the results of the present study and on observations reported in the literature, we propose that the intestinal tract contains a sodium "sensor", which upon activation releases a natriuretic factor to cause renal sodium excretion. The present results indicate that the proposed "sensor" is sensitive to lithium but not chloride ions.

Blueberry Husks and Probiotics Attenuate Colorectal Inflammation and Oncogenesis, and Liver Injuries in Rats Exposed to Cycling DSS-Treatment

PubMed Central

Håkansson, Åsa; Bränning, Camilla; Molin, Göran; Adawi, Diya; Hagslätt, Marie-Louise; Jeppsson, Bengt; Nyman, Margareta; Ahrné, Siv

2012-01-01

Long-term colonic inflammation promotes carcinogenesis and histological abnormalities of the liver, and colorectal tumours frequently arise in a background of dysplasia, a precursor of adenomas. Altered colonic microbiota with an increased proportion of bacteria with pro-inflammatory characteristics, have been implicated in neoplastic progression. The composition of the microbiota can be modified by dietary components such as probiotics, polyphenols and dietary fibres. In the present study, the influence of probiotics in combination with blueberry husks on colorectal carcinogenesis and subsequent liver damage was evaluated. Colorectal tumours were induced in rats by cyclic treatment with dextran sulphate sodium (DSS). Blueberry husks and a mixture of three probiotic strains (Bifidobacterium infantis DSM 15159, Lactobacillus gasseri, DSM 16737 and Lactobacillus plantarum DSM 15313) supplemented a basic diet fortified with oats. The condition of the rats was monitored using a disease activity index (DAI). A qualitative and quantitative histological judgement was performed on segments of distal colon and rectum and the caudate lobe of the liver. The formation of short-chain fatty acids, bacterial translocation, the inflammatory reaction and viable count of lactobacilli and Enterobaceriaceae were addressed. Blueberry husks with or without probiotics significantly decreased DAI, and significantly reduced the number of colonic ulcers and dysplastic lesions. With a decreased proportion of blueberry husk in the diet, the probiotic supplement was needed to achieve a significant decrease in numbers of dysplastic lesions. Probiotics decreased faecal viable count of Enterobacteriaceae and increased that of lactobacilli. Blueberry husks with or without probiotics lowered the proportion of butyric acid in distal colon, and decreased the haptoglobin levels. Probiotics mitigated hepatic injuries by decreasing parenchymal infiltration and the incidence of stasis and translocation

Salt Sensitivity and Hypertension: A Paradigm Shift from Kidney Malfunction to Vascular Endothelial Dysfunction

PubMed Central

Choi, Hoon Young; Park, Hyeong Cheon

2015-01-01

Hypertension is a complex trait determined by both genetic and environmental factors and is a major public health problem due to its high prevalence and concomitant increase in the risk for cardiovascular disease. With the recent large increase of dietary salt intake in most developed countries, the prevalence of hypertension increases tremendously which is about 30% of the world population. There is substantial evidence that suggests some people can effectively excrete high dietary salt intake without an increase in arterial BP, and another people cannot excrete effectively without an increase in arterial BP. Salt sensitivity of BP refers to the BP responses for changes in dietary salt intake to produce meaningful BP increases or decreases. The underlying mechanisms that promote salt sensitivity are complex and range from genetic to environmental influences. The phenotype of salt sensitivity is therefore heterogeneous with multiple mechanisms that potentially link high salt intake to increases in blood pressure. Moreover, excess salt intake has functional and pathological effects on the vasculature that are independent of blood pressure. Epidemiologic data demonstrate the role of high dietary salt intake in mediating cardiovascular and renal morbidity and mortality. Almost five decades ago, Guyton and Coleman proposed that whenever arterial pressure is elevated, pressure natriuresis enhances the excretion of sodium and water until blood volume is reduced sufficiently to return arterial pressure to control values. According to this hypothesis, hypertension can develop only when something impairs the excretory ability of sodium in the kidney. However, recent studies suggest that nonosmotic salt accumulation in the skin interstitium and the endothelial dysfunction which might be caused by the deterioration of vascular endothelial glycocalyx layer (EGL) and the epithelial sodium channel on the endothelial luminal surface (EnNaC) also play an important role in

Antihypertensive activities of the aqueous extract of Kalanchoe pinnata (Crassulaceae) in high salt-loaded rats.

PubMed

Bopda, Orelien Sylvain Mtopi; Longo, Frida; Bella, Thierry Ndzana; Edzah, Protais Marcellin Ohandja; Taïwe, Germain Sotoing; Bilanda, Danielle Claude; Tom, Esther Ngo Lemba; Kamtchouing, Pierre; Dimo, Theophile

2014-04-28

The leaves of Kalanchoe pinnata (Crassulaceae) are used in Cameroon folk medicine to manage many diseases such as cardiovascular dysfunctions. In this work, we aimed to evaluate the activities of aqueous leaf extract of Kalanchoe pinnata on the blood pressure of normotensive rat (NTR) and salt hypertensive rats (SHR), as well as its antioxidant properties. Hypertension was induced in rats by oral administration of 18% NaCl for 4 weeks. For the preventive study, three groups of rats received 18% NaCl solution and the plant extract at 25 mg/kg/day, 50 mg/kg/day or 100 mg/kg/day by gavage. Two positive control groups received 18% NaCl solution and either spironolactone (0.71 mg/kg/day) or eupressyl (0.86 mg/kg/day) by gavage for 4 weeks. At the end of this experimental period, systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and heart rate (HR) were measured by the invasive method. Some oxidative stress biomarkers (reduced glutathione (GSH), superoxide dismutase (SOD), nitric monoxide (NO) were evaluated in heart, aorta, liver and kidney. NO level was indirectly evaluated by measuring nitrite concentration. Kalanchoe pinnata extract prevented significantly the increase of systolic and diastolic arterial pressures in high salt-loaded rats (SHR). In SHR, concomitant administration of Kalanchoe pinnata at 25, 50 and 100 mg/kg/day significantly prevented the increase in blood pressure by 32%, 24% and 47% (for SAP); 35%, 33% and 56% (for DAP), respectively. No significant change was recorded in heart rate of those rats. The plant extract improved antioxidant status in various organs, but more potently in aorta. Thus, antioxidant and modulatory effects of Kalanchoe pinnata at the vasculature might be of preponderant contribution to its overall antihypertensive activity. The work demonstrated that the concomitant administration of high-salt and the aqueous extract of Kalanchoe pinnata elicits prevention of salt-induced hypertension in rat. This

Role of Vasopressin in Rat Models of Salt-Dependent Hypertension.

PubMed

Prager-Khoutorsky, Masha; Choe, Katrina Y; Levi, David I; Bourque, Charles W

2017-05-01

Dietary salt intake increases both plasma sodium and osmolality and therefore increases vasopressin (VP) release from the neurohypophysis. Although this effect could increase blood pressure by inducing fluid reabsorption and vasoconstriction, acute activation of arterial baroreceptors inhibits VP neurons via GABA A receptors to oppose high blood pressure. Here we review recent findings demonstrating that this protective mechanism fails during chronic high salt intake in rats. Two recent studies showed that chronic high sodium intake causes an increase in intracellular chloride concentration in VP neurons. This effect causes GABA A receptors to become excitatory and leads to the emergence of VP-dependent hypertension. One study showed that the increase in intracellular chloride was provoked by a decrease in the expression of the chloride exporter KCC2 mediated by local secretion of brain-derived neurotrophic factor and activation of TrkB receptors. Prolonged high dietary salt intake can cause pathological plasticity in a central homeostatic circuit that controls VP secretion and thereby contribute to peripheral vasoconstriction and hypertension.

A DSS for sustainable development and environmental protection of agricultural regions.

PubMed

Manos, Basil D; Papathanasiou, Jason; Bournaris, Thomas; Voudouris, Kostas

2010-05-01

This paper presents a decision support system (DSS) for sustainable development and environmental protection of agricultural regions developed in the framework of the Interreg-Archimed project entitled WaterMap (development and utilization of vulnerability maps for the monitoring and management of groundwater resources in the ARCHIMED areas). Its aim is to optimize the production plan of an agricultural region taking in account the available resources, the environmental parameters, and the vulnerability map of the region. The DSS is based on an optimization multicriteria model. The spatial integration of vulnerability maps in the DSS enables regional authorities to design policies for optimal agricultural development and groundwater protection from the agricultural land uses. The DSS can further be used to simulate different scenarios and policies by the local stakeholders due to changes on different social, economic, and environmental parameters. In this way, they can achieve alternative production plans and agricultural land uses as well as to estimate economic, social, and environmental impacts of different policies. The DSS is computerized and supported by a set of relational databases. The corresponding software has been developed in a Microsoft Windows XP platform, using Microsoft Visual Basic, Microsoft Access, and the LINDO library. For demonstration reasons, the paper includes an application of the DSS in a region of Northern Greece.

Telmisartan improves survival and ventricular function in SHR rats with extensive cardiovascular damage induced by dietary salt excess.

PubMed

Susic, Dinko; Frohlich, Edward D

2014-05-01

Excessive dietary salt intake induces extensive cardiovascular and renal damage in spontaneously hypertensive rats (SHR) that may be prevented by antihypertensive agents. This study examines whether salt-induced cardiac damage may be reversed by angiotensin II (type 1) receptor blockade (telmisartan). Eight-week-old male SHRs were divided into four groups; Group 1 (NS) was fed regular rat chow, and Group 2 (HS) received high-salt diet (HS; 8% NaCl). After 8 weeks on their respective diets, systemic hemodynamics and indices of left ventricular (LV) function were determined. Group 3 (HSnoT) was given HS for 8 weeks and then switched to a regular chow (0.6% NaCl) diet with no other treatment, and Group 4 (HSArb) received HS for 8 weeks and was then given regular diet plus telmisartan. Rats from these latter two groups were monitored for the ensuing 30 days. Compared with the NS group, rats in the HS group exhibited increased mean arterial pressure (161 ± 7 vs. 184 ± 8 mm Hg) and LV diastolic dysfunction, as evidenced by a decreased rate of LV pressure decline (-8754 ± 747 vs. -4234 ± 754 mmHg/sec) at the end of the 8 weeks of their respective treatment. After switching to regular chow, only one of 11 rats in the HSnoT group survived for the 30 days, whereas 10 died within 18 days; in the HSArb group only one of nine rats died; eight survived 30 days (P < .01). Telmisartan significantly improved LV function and survival in those SHR rats having extensive cardiovascular damage induced by dietary salt excess. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Reactive oxygen species dynamics in roots of salt sensitive and salt tolerant cultivars of rice.

PubMed

Saini, Shivani; Kaur, Navdeep; Pati, Pratap Kumar

2018-06-01

Salinity stress is one of the major constraints for growth and survival of plants that affects rice productivity worldwide. Hence, in the present study, roots of two contrasting salinity sensitive cultivars, IR64 (IR64, salt sensitive) and Luna Suvarna (LS, salt tolerant) were compared with regard to the levels of reactive oxygen species (ROS) to derive clues for their differential salt stress adaptation mechanisms. In our investigation, the tolerant cultivar exhibited longer primary roots, more lateral roots, higher root number leading to increased root biomass, with respect to IR64. It was observed that LS roots maintained higher level of H 2 O 2 in comparison to IR64. The activities of various enzymes involved in enzymatic antioxidant defense mechanism (SOD, CAT, GPX, DHAR and MDHAR) were found to be greater in LS roots. Further, the higher transcript level accumulation of genes encoding ROS generating (RbohA, RbohD and RbohE) and scavenging enzymes (Fe-SOD, Chloroplastic Cu/Zn-SOD, CAT and DHAR) were noticed in the roots of tolerant cultivar, LS. Moreover, the content of other stress markers such as total protein and proline were also elevated in LS roots. While, the expression of proline biosynthesis gene (P5CS) and proline catabolism gene (PDH) was observed to be lower in LS. Copyright © 2018. Published by Elsevier Inc.

Computational Analysis of Candidate Disease Genes and Variants for Salt-Sensitive Hypertension in Indigenous Southern Africans

PubMed Central

Tiffin, Nicki; Meintjes, Ayton; Ramesar, Rajkumar; Bajic, Vladimir B.; Rayner, Brian

2010-01-01

Multiple factors underlie susceptibility to essential hypertension, including a significant genetic and ethnic component, and environmental effects. Blood pressure response of hypertensive individuals to salt is heterogeneous, but salt sensitivity appears more prevalent in people of indigenous African origin. The underlying genetics of salt-sensitive hypertension, however, are poorly understood. In this study, computational methods including text- and data-mining have been used to select and prioritize candidate aetiological genes for salt-sensitive hypertension. Additionally, we have compared allele frequencies and copy number variation for single nucleotide polymorphisms in candidate genes between indigenous Southern African and Caucasian populations, with the aim of identifying candidate genes with significant variability between the population groups: identifying genetic variability between population groups can exploit ethnic differences in disease prevalence to aid with prioritisation of good candidate genes. Our top-ranking candidate genes include parathyroid hormone precursor (PTH) and type-1angiotensin II receptor (AGTR1). We propose that the candidate genes identified in this study warrant further investigation as potential aetiological genes for salt-sensitive hypertension. PMID:20886000

Increased Renal Iron Accumulation in Hypertensive Nephropathy of Salt-Loaded Hypertensive Rats

PubMed Central

Naito, Yoshiro; Sawada, Hisashi; Oboshi, Makiko; Fujii, Aya; Hirotani, Shinichi; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Eguchi, Akiyo; Morisawa, Daisuke; Ohyanagi, Mitsumasa; Tsujino, Takeshi; Masuyama, Tohru

2013-01-01

Although iron is reported to be associated with the pathogenesis of chronic kidney disease, it is unknown whether iron participates in the pathophysiology of nephrosclerosis. Here, we investigate whether iron is involved in the development of hypertensive nephropathy and the effects of iron restriction on nephrosclerosis in salt- loaded stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were given either a normal or high-salt diet for 8 weeks. Another subset of SHRSP were fed a high-salt with iron-restricted diet. SHRSP given a high-salt diet developed severe hypertension and nephrosclerosis. As a result, survival rate was decreased after 8 weeks diet. Importantly, massive iron accumulation and increased iron content were observed in the kidneys of salt-loaded SHRSP, along with increased superoxide production, urinary 8-Hydroxy-2′-deoxyguanosine excretion, and urinary iron excretion; however, these changes were markedly attenuated by iron restriction. Of interest, expression of cellular iron transport proteins, transferrin receptor 1 and divalent metal transporter 1, was increased in the tubules of salt-loaded SHRSP. Notably, iron restriction attenuated the development of severe hypertension and nephrosclerosis, thereby improving survival rate in salt-loaded SHRSP. Taken together, these results suggest a novel mechanism by which iron plays a role in the development of hypertensive nephropathy and establish the effects of iron restriction on salt-induced nephrosclerosis. PMID:24116080

Absence of stearoyl-CoA desaturase-1 does not promote DSS-induced acute colitis.

PubMed

Macdonald, Marcia L E; Bissada, Nagat; Vallance, Bruce A; Hayden, Michael R

2009-12-01

Absence of stearoyl-CoA desaturase-1 (SCD1) in mice leads to chronic inflammation of the skin and increased susceptibility to atherosclerosis, while also increasing plasma inflammatory markers. A recent report suggested that SCD1 deficiency also increases disease severity in a mouse model of inflammatory bowel disease, induced by dextran sulfate sodium (DSS). However, SCD1-deficient mice are known to consume increased amounts of water, which would also be expected to increase the intake of DSS-treated water. The aim of this study was to determine the effect of SCD1 deficiency on DSS-induced acute colitis with DSS dosing adjusted to account for genotype differences in fluid consumption. Wild-type controls were treated with 3.5% DSS for 5 days to induce moderately severe colitis, while the concentration of DSS given to SCD1-deficient mice was lowered to 2.5% to control for increased fluid consumption. Colonic inflammation was assessed by clinical and histological scoring. Although SCD1-deficient mice consumed a total intake of DSS that was greater than that of wild-type controls, colonic inflammation, colon length and fecal blood were not altered by SCD1-deficiency in DSS-induced colitis, while diarrhea and total weight loss were modestly improved. Despite SCD1 deficiency leading to chronic inflammation of the skin and increased susceptibility to atherosclerosis, it does not accelerate inflammation in the DSS-induced model of acute colitis when DSS intake is controlled. These observations suggest that SCD1 deficiency does not play a significant role in colonic inflammation in this model.

Renal inflammation, autoimmunity and salt-sensitive hypertension

PubMed Central

Rodríguez-Iturbe, Bernardo; Franco, Martha; Tapia, Edilia; Quiroz, Yasmir; Johnson, Richard J

2011-01-01

This article reviews the role of immune competent cells infiltrating the kidney and their association with oxidative stress and renal angiotensin activity in the development of salt-sensitive hypertension.We discuss the alteration of the pressure-natriuresis relationship resulting from renal inflammation and its improvement resulting from immunosuppressive treatment.The potential role of T cell-driven reactivity in sustaining the renal inflammation is examined in the light of accumulating evidence of autoimmune mechanisms in experimental and clinical hypertension. PMID:21251049

[A cross-racial analysis on the susceptible gene polymorphisms of salt-sensitive hypertension].

PubMed

Lu, Jia-peng; Zhang, Ling; Wang, Wei

2010-10-01

To compare the genetic distributions of salt-sensitivity of four ethnic populations in Hapmap database. The frequencies data (395 subjects) of salt-sensitivity polymorphisms (AGT/M235T, ACE/ID, CYP11B2/C-344T, ADDI/Gly460Trp, GNB3/C825 and CYP3A5/A6986G)of Utah residents with ancestry from northern and western Europe (CEU), Han Chinese in Beijing (CHB), Japanese in Tokyo (JPT) and Yoruba mother-father-child trios in Ibadan, Nigeria (YRI) were obtained from International HapMap Project. The good-fit χ(2) test was performed to test whether the frequencies of each genotype reached Hardy-Weinberg equilibrium. The differences of the genotype and allele distribution and trend analysis were detected via χ(2) test. Furthermore, multiple comparisons between two populations were analyzed by Lancaster's partition of chi-squares. There were significant differences of each genotype distribution among four ethnic populations (P < 0.05). The distribution of genotype frequencies and susceptible allele frequencies of salt sensitive candidate genes were similar between CHB and JPT. Excepted for GNB3/825T allele (38.8% vs.34.4%, P = 0.521), susceptible allele frequencies in AGT/235T (79.2% vs. 41.2%, P < 0.001), ACE/I (56.5% vs. 43.5%, P < 0.001), CYP11B2/-344T (74.1% vs. 56.7%, P = 0.001), ADDI/460Trp (51.8% vs. 20.4%, P < 0.001) and CYP3A5/A6986 (30.1% vs. 3.6%, P < 0.001) were significantly higher in CHB than in CEU. There distribution of ADDI/460Trp allele was significant lower in YRI (4%) than in CHB (51.8%, P < 0.001). However frequencies of AGT/235T, CYP11B2/-334T, GNB3/825T and CYP3A5/6986A in CHB were significantly lower than those in YRI (P < 0.05). Trend analyses showed significantly increased trend in AGT/235T (41.2% < 79.2% < 92.0%, P < 0.001), CYP11B2/-334T (56.7% < 74.1% < 84.8%, P < 0.001) and CYP3A5/6986A (3.6% < 30.1% < 84.5%, P < 0.001) in CEU, CHB and YRI. There are significant discrepancy of salt-sensitivity variant distributions among four ethnic populations

INCREASED RENAL OXIDATIVE STRESS IN SALT-SENSITIVE HUMAN GRK4γ486V TRANSGENIC MICE

PubMed Central

Diao, Zhenyu; Asico, Laureano D.; Villar, Van Anthony M.; Zheng, Xiaoxu; Cuevas, Santiago; Armando, Ines; Jose, Pedro A.; Wang, Xiaoyan

2017-01-01

We tested the hypothesis that salt-sensitive hypertension is caused by renal oxidative stress by measuring the blood pressure and reactive oxygen species-related proteins in the kidneys of human G protein-coupled receptor kinase 4γ (hGRK4γ) 486V transgenic mice and non-transgenic (Non-T) littermates on normal and high salt diets. High salt diet increased the blood pressure, associated with impaired sodium excretion, in hGRK4γ486V mice. Renal expressions of NOX isoforms were similar in both strains on normal salt diet but NOX2 was decreased by high salt diet to a greater extent in Non-T than hGRK4γ486V mice. Renal HO-2, but not HO-1, protein was greater in hGRK4γ486V than Non-T mice on normal salt diet and normalized by high salt diet. On normal salt diet, renal CuZnSOD and ECSOD proteins were similar but renal MnSOD was lower in hGRK4γ486V than Non-T mice and remained low on high salt diet. High salt diet decreased renal CuZnSOD in hGRK4γ486V but not Non-T mice and decreased renal ECSOD to a greater extent in hGRK4γ486V than Non-T mice. Renal SOD activity, superoxide production, and NOS3 protein were similar in two strains on normal salt diet. However, high salt diet decreased SOD activity and NOS3 protein and increased superoxide production in hGRK4γ486V mice but not in Non-T mice. High salt diet also increased urinary 8-isoprostane and 8-hydroxydeoxyguanosine to a greater extent in hGRK4γ486V than Non-T mice. hGRK4γwild-type mice were normotensive and hGRK4γ142V mice were hypertensive but both were salt-resistant and in normal redox balance. Chronic tempol treatment partially prevented the salt-sensitivity of hGRK4γ486V mice. Thus, hGRK4γ486V causes salt-sensitive hypertension due, in part, to defective renal antioxidant mechanisms. PMID:28189851

Ethanol modulates the VR-1 variant amiloride-insensitive salt taste receptor. II. Effect on chorda tympani salt responses.

PubMed

Lyall, Vijay; Heck, Gerard L; Phan, Tam-Hao T; Mummalaneni, Shobha; Malik, Shahbaz A; Vinnikova, Anna K; Desimone, John A

2005-06-01

The effect of ethanol on the amiloride- and benzamil (Bz)-insensitive salt taste receptor was investigated by direct measurement of intracellular Na(+) activity ([Na(+)](i)) using fluorescence imaging in polarized fungiform taste receptor cells (TRCs) and by chorda tympani (CT) taste nerve recordings. CT responses to KCl and NaCl were recorded in Sprague-Dawley rats, and in wild-type (WT) and vanilloid receptor-1 (VR-1) knockout mice (KO). CT responses were monitored in the presence of Bz, a specific blocker of the epithelial Na(+) channel (ENaC). CT responses were also recorded in the presence of agonists (resiniferatoxin and elevated temperature) and antagonists (capsazepine and SB-366791) of VR-1 that similarly modulate the Bz-insensitive VR-1 variant salt taste receptor. In the absence of mineral salts, ethanol induced a transient decrease in TRC volume and elicited only transient phasic CT responses. In the presence of mineral salts, ethanol increased the apical cation flux in TRCs without a change in volume, increased transepithelial electrical resistance across the tongue, and elicited CT responses that were similar to salt responses, consisting of both a phasic component and a sustained tonic component. At concentrations <50%, ethanol enhanced responses to KCl and NaCl, while at ethanol concentrations >50%, those CT responses were inhibited. Resiniferatoxin and elevated temperature increased the sensitivity of the CT response to ethanol in salt-containing media, and SB-366791 inhibited the effect of ethanol, resiniferatoxin, and elevated temperature on the CT responses to mineral salts. VR-1 KO mice demonstrated no Bz-insensitive CT response to NaCl and no sensitivity to ethanol. We conclude that ethanol increases salt taste sensitivity by its direct action on the Bz-insensitive VR-1 variant salt taste receptor.

Danshensu-mediated protective effect against hepatic fibrosis induced by carbon tetrachloride in rats.

PubMed

Qu, W; Huang, H; Li, K; Qin, C

2014-12-01

The culprit of hepatic fibrosis (HF) is linked to suprathreshold deposition of collagen. Thus, collagen reduction by improved metabolism contributes to HF management. In this study, we aimed to investigate the hepatoprotective effects of Danshensu (DSS) against carbon tetrachloride (CCl4)-induced HF rats. The results showed that DSS-administrated rats resulted in decreasing in hepatosomatic indexes, and lowering serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Meanwhile, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were increased, while the content of malonaldehyde (MDA) was lessened in liver tissue of DSS administration group. In addition, the pro-fibrotic markers of hydroxyproline (Hyp), type III procollagen (PCIII) and hyaluronic acid (HA) contents were decreased. Histopathological examination confirmed that the hepatotoxicity in CCl4-injured rats was alleviated following the DSS administration. Furthermore, intrahepatic protein expressions of alpha-smooth muscle actin (α-SMA), phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) were effectively down-regulated, respectively. Overall, this work demonstrates that DSS played the protective effect against CCl4-induced cytotoxicity in liver tissue, which the probable mechanism is associated with attenuation of lipid peroxidation, collagen accumulation and enhancement of anti-oxidative defense capability, as well as regulation of intrahepatic JAK/STAT pathway for maintaining collagenic homoeostasis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Salt stress induces differential regulation of the phenylpropanoid pathway in Olea europaea cultivars Frantoio (salt-tolerant) and Leccino (salt-sensitive).

PubMed

Rossi, Lorenzo; Borghi, Monica; Francini, Alessandra; Lin, Xiuli; Xie, De-Yu; Sebastiani, Luca

2016-10-01

Olive tree (Olea europaea L.) is an important crop in the Mediterranean Basin where drought and salinity are two of the main factors affecting plant productivity. Despite several studies have reported different responses of various olive tree cultivars to salt stress, the mechanisms that convey tolerance and sensitivity remain largely unknown. To investigate this issue, potted olive plants of Leccino (salt-sensitive) and Frantoio (salt-tolerant) cultivars were grown in a phytotron chamber and treated with 0, 60 and 120mM NaCl. After forty days of treatment, growth analysis was performed and the concentration of sodium in root, stem and leaves was measured by atomic absorption spectroscopy. Phenolic compounds were extracted using methanol, hydrolyzed with butanol-HCl, and quercetin and kaempferol quantified via high performance liquid-chromatography-electrospray-mass spectrometry (HPLC-ESI-MS) and HPLC-q-Time of Flight-MS analyses. In addition, the transcripts levels of five key genes of the phenylpropanoid pathway were measured by quantitative Real-Time PCR. The results of this study corroborate the previous observations, which showed that Frantoio and Leccino differ in allocating sodium in root and leaves. This study also revealed that phenolic compounds remain stable or are strongly depleted under long-time treatment with sodium in Leccino, despite a strong up-regulation of key genes of the phenylpropanoid pathway was observed. Frantoio instead, showed a less intense up-regulation of the phenylpropanoid genes but overall higher content of phenolic compounds. These data suggest that Frantoio copes with the toxicity imposed by elevated sodium not only with mechanisms of Na + exclusion, but also promptly allocating effective and adequate antioxidant compounds to more sensitive organs. Copyright © 2016 Elsevier GmbH. All rights reserved.

32 CFR 321.8 - DSS review of request for amendment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.8 DSS review of request for... himself and maintained by the Defense Security Service, Office of FOI and Privacy will handle the request... 32 National Defense 2 2012-07-01 2012-07-01 false DSS review of request for amendment. 321.8...

32 CFR 321.8 - DSS review of request for amendment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.8 DSS review of request for... himself and maintained by the Defense Security Service, Office of FOI and Privacy will handle the request... 32 National Defense 2 2010-07-01 2010-07-01 false DSS review of request for amendment. 321.8...

32 CFR 321.8 - DSS review of request for amendment.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.8 DSS review of request for... himself and maintained by the Defense Security Service, Office of FOI and Privacy will handle the request... 32 National Defense 2 2011-07-01 2011-07-01 false DSS review of request for amendment. 321.8...

32 CFR 321.8 - DSS review of request for amendment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.8 DSS review of request for... himself and maintained by the Defense Security Service, Office of FOI and Privacy will handle the request... 32 National Defense 2 2013-07-01 2013-07-01 false DSS review of request for amendment. 321.8...

32 CFR 321.8 - DSS review of request for amendment.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) PRIVACY PROGRAM DEFENSE SECURITY SERVICE PRIVACY PROGRAM § 321.8 DSS review of request for... himself and maintained by the Defense Security Service, Office of FOI and Privacy will handle the request... 32 National Defense 2 2014-07-01 2014-07-01 false DSS review of request for amendment. 321.8...

Low-salt diet enhances vascular reactivity and Ca(2+) entry in pregnant rats with normal and reduced uterine perfusion pressure.

PubMed

Giardina, Jena B; Cockrell, Kathy L; Granger, Joey P; Khalil, Raouf A

2002-02-01

Salt moderation is often recommended to prevent excessive increases in blood pressure during pregnancy, particularly in women who are prone to pregnancy-induced hypertension; however, the vascular effects of low dietary salt intake during pregnancy are unclear. We investigated whether a low-salt diet during pregnancy alters the mechanisms of vascular smooth muscle contraction. Active stress and (45)Ca(2+) influx were measured in endothelium-denuded aortic strips of virgin and normal pregnant Sprague-Dawley rats and a hypertensive pregnant rat model produced by reduction in uterine perfusion pressure (RUPP), fed either a normal-sodium (NS, 1% NaCl) or low-sodium diet (LS, 0.2% NaCl) for 7 days. The mean arterial pressure was as follows: virgin/NS 108 +/- 8, virgin/LS 117 +/- 7, pregnant/NS 102 +/- 3, pregnant/LS 117 +/- 4, RUPP/NS 119 +/- 3, and RUPP/LS 133 +/- 6 mm Hg. Phenylephrine (Phe) caused concentration-dependent increases in active stress and (45)Ca(2+) influx that were greater in RUPP rats than in normal pregnant or virgin rats and were enhanced in pregnant/LS and RUPP/LS compared with pregnant/NS and RUPP/NS, respectively. High KCl (16 to 96 mmol/L), which stimulates Ca(2+) entry from the extracellular space, also caused increases in active stress that were greater in RUPP than in normal pregnant, in pregnant/LS than in pregnant/NS, and in RUPP/LS than in RUPP/NS rats. The Phe-induced (45)Ca(2+) influx--active stress relation was greater in RUPP/NS than in pregnant/NS and was enhanced in pregnant/LS and RUPP/LS compared with pregnant/NS and RUPP/NS, respectively. In Ca(2+)-free (2 mmol/L ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetra-acetic acid) Krebs, stimulation of intracellular Ca(2+) release by Phe (10(-5) mol/L) or caffeine (25 mmol/L) caused a transient contraction that was not significantly different in all groups of rats. Thus, a low-salt diet in pregnant and RUPP rats is associated with increases in vascular reactivity that involves Ca

Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlation with salt sensitivity in normal subjects.

PubMed

ter Maaten, J C; Bakker, S J; Serné, E H; ter Wee, P M; Donker, A J; Gans, R O

1999-10-01

Insulin induces sodium retention by increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects could link insulin resistance to blood-pressure elevation and salt sensitivity. We assessed the relationship between the effects of sequential physiological and supraphysiological insulin dosages (50 and 150 mU/kg/h) on renal sodium handling, and insulin sensitivity and salt sensitivity using the euglycaemic clamp technique and clearances of [131I]hippuran, [125I]iothalamate, sodium, and lithium in 20 normal subjects displaying a wide range of insulin sensitivity. Time-control experiments were performed in the same subjects. Salt sensitivity was determined using a diet method. During the successive insulin infusions, GFR increased by 5.9% (P = 0.003) and 10.9% (P<0.001), while fractional sodium excretion decreased by 34 and 50% (both P<0.001). Distal tubular sodium reabsorption increased and proximal tubular sodium reabsorption decreased. Insulin sensitivity correlated with changes in GFR during physiological (r = 0.60, P = 0.005) and supraphysiological (r = 0.58, P = 0.007) hyperinsulinaemia, but not with changes in proximal tubular sodium reabsorption. Salt sensitivity correlated with changes in proximal tubular sodium reabsorption (r = 0.49, P = 0.028), but not in GFR, during physiological hyperinsulinaemia. Neither insulin sensitivity or salt sensitivity correlated with changes in overall fractional sodium excretion. Insulin sensitivity and salt sensitivity correlate with changes in different elements of renal sodium handling, but not with overall sodium excretion, during insulin infusion. The relevance for blood pressure regulation remains to be proved.

Salt acclimation process: a comparison between a sensitive and a tolerant Olea europaea cultivar.

PubMed

Pandolfi, Camilla; Bazihizina, Nadia; Giordano, Cristiana; Mancuso, Stefano; Azzarello, Elisa

2017-03-01

Saline soils are highly heterogeneous in time and space, and this is a critical factor influencing plant physiology and productivity. Temporal changes in soil salinity can alter plant responses to salinity, and pre-treating plants with low NaCl concentrations has been found to substantially increase salt tolerance in different species in a process called acclimation. However, it still remains unclear whether this process is common to all plants or is only expressed in certain genotypes. We addressed this question by assessing the physiological changes to 100 mM NaCl in two contrasting olive cultivars (the salt-sensitive Leccino and the salt-tolerant Frantoio), following a 1-month acclimation period with 5 or 25 mM NaCl. The acclimation improved salt tolerance in both cultivars, but activated substantially different physiological adjustments in the tolerant and the sensitive cultivars. In the tolerant Frantoio the acclimation with 5 mM NaCl was more effective in increasing plant salt tolerance, with a 47% increase in total plant dry mass compared with non-acclimated saline plants. This enhanced biomass accumulation was associated with a 50% increase in K+ retention ability in roots. On the other hand, in the sensitive Leccino, although the acclimation process did not improve performance in terms of plant growth, pre-treatment with 5 and 25 mM NaCl substantially decreased salt-induced leaf cell ultrastructural changes, with leaf cell relatively similar to those of control plants. Taken together these results suggest that in the tolerant cultivar the acclimation took place primarily in the root tissues, while in the sensitive they occurred mainly at the shoot level. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Increased sensitivity to salt stress in tocopherol-deficient Arabidopsis mutants growing in a hydroponic system

PubMed Central

Ellouzi, Hasna; Hamed, Karim Ben; Cela, Jana; Müller, Maren; Abdelly, Chedly; Munné-Bosch, Sergi

2013-01-01

Recent studies suggest that tocopherols could play physiological roles in salt tolerance but the mechanisms are still unknown. In this study, we analyzed changes in growth, mineral and oxidative status in vte1 and vte4 Arabidopsis thaliana mutants exposed to salt stress. vte1 and vte4 mutants lack α-tocopherol, but only the vte1 mutant is additionally deficient in γ-tocopherol. Results showed that a deficiency in vitamin E leads to reduced growth and increased oxidative stress in hydroponically-grown plants. This effect was observed at early stages, not only in rosettes but also in roots. The vte1 mutant was more sensitive to salt-induced oxidative stress than the wild type and the vte4 mutant. Salt sensitivity was associated with (i) high contents of Na+, (ii) reduced efficiency of PSII photochemistry (Fv/Fm ratio) and (iii) more pronounced oxidative stress as indicated by increased hydrogen peroxide and malondialdeyde levels. The vte 4 mutant, which accumulates γ- instead of α-tocopherol showed an intermediate sensitivity to salt stress between the wild type and the vte1 mutant. Contents of abscisic acid, jasmonic acid and the ethylene precursor, 1-aminocyclopropane-1-carboxylic acid were higher in the vte1 mutant than the vte4 mutant and wild type. It is concluded that vitamin E-deficient plants show an increased sensitivity to salt stress both in rosettes and roots, therefore indicating the positive role of tocopherols in stress tolerance, not only by minimizing oxidative stress, but also controlling Na+/K+ homeostasis and hormonal balance. PMID:23299430

Parenteral nutrition dysregulates bile salt homeostasis in a rat model of parenteral nutrition-associated liver disease.

PubMed

Koelfat, Kiran V K; Schaap, Frank G; Hodin, Caroline M J M; Visschers, Ruben G J; Svavarsson, Björn I; Lenicek, Martin; Shiri-Sverdlov, Ronit; Lenaerts, Kaatje; Olde Damink, Steven W M

2017-10-01

Parenteral nutrition (PN), a lifesaving therapy in patients with intestinal failure, has been associated with hepatobiliary complications including steatosis, cholestasis and fibrosis, collectively known as parenteral nutrition-associated liver disease (PNALD). To date, the pathogenesis of PNALD is poorly understood and therapeutic options are limited. Impaired bile salt homeostasis has been proposed to contribute PNALD. The objective of this study was to establish a PNALD model in rats and to evaluate the effects of continuous parenteral nutrition (PN) on bile salt homeostasis. Rats received either PN via the jugular vein or received normal diet for 3, 7 or 14 days. Serum biochemistry, hepatic triglycerides, circulating bile salts and C4, IL-6 and TNF-alpha, and lipogenic and bile salt homeostatic gene expression in liver and ileum were assessed. PN increased hepatic triglycerides already after 3 days of administration, and resulted in conjugated bilirubin elevation after 7 or more days. This indicates PN-induced steatosis and impaired canalicular secretion of bilirubin, the latter which is in line with reduced hepatic expression of Mrp2 mRNA. There was no histological evidence for liver inflammation after PN administration, and circulating levels of pro-inflammatory cytokines IL-6 and TNF-α, were comparable in all groups. Hepatic expression of Fxr mRNA was decreased after 7 days of PN, without apparent effect on expression of Fxr targets Bsep and Shp. Nonetheless, Cyp7a1 expression was reduced after 7 days of PN, indicative for lowered bile salt synthesis. Circulating levels of C4 (marker of bile salt synthesis) were also decreased after 3, 7 and 14 days of PN. Levels of circulating bile salts were not affected by PN. This study showed that PN in rats caused early mild steatosis and cholestasis, while hepatic and systemic inflammation were not present. The onset of these abnormalities was associated with alterations in bile salt synthesis and transport. This

Salt sensitivity in normotensives with family history of hypertension: studies of membrane transport, intracellular electrolytes and alpha 2-adrenergic receptors.

PubMed

Skrabal, F; Gruber, G; Meister, B; Ledochowski, M; Doll, P; Lang, F; Cerny, E

1985-12-01

Using long-term automatic blood pressure recording it has previously been shown that subjects with family history of hypertension show a minute fall of blood pressure during sodium restriction, which is reversible by high sodium intake. Thus normotensives with hypertensive antecedents as a group are salt-sensitive, whereas normotensives without heredity of hypertension as a group are salt-resistant. The present study compares intracellular sodium, potassium and calcium, sodium pump activity, NaK-cotransport of red blood cells and density and affinity of alpha 2-adrenergic receptors of platelets in normotensive subjects classified according to family history of hypertension and according to 'salt sensitivity' and 'salt resistance'. Neither the family history of hypertension nor salt sensitivity correlated with intracellular sodium, potassium, calcium, Na-pump activity and NaK-cotransport. Alpha 2-adrenergic density was higher in salt-sensitive than in salt-resistant subjects (P < 0.05) but similar in subjects with a positive and negative family history of hypertension. However, alpha 2-adrenergic receptor density decreased significantly during 2 weeks of moderate salt restriction from 169.6 +/- 34.2 to 142.6 +/- 30.8 (P < 0.01, paired t-test), which may explain the decreased pressor response to infused noradrenaline observed in a previous study during moderate salt restriction. It is concluded that in humans there is no association of genetic predisposition of hypertension or of salt sensitivity to an alteration of sodium pump activity, NaK-cotransport, intracellular sodium and calcium. Alpha 2-receptor density of platelets deserves further study as a possible predictor of salt sensitivity in normotensives.

Chronic Supplementation of Paeonol Combined with Danshensu for the Improvement of Vascular Reactivity in the Cerebral Basilar Artery of Diabetic Rats

PubMed Central

Hu, Jing; Li, Ya-Ling; Li, Zi-Lin; Li, Hua; Zhou, Xuan-Xuan; Qiu, Peng-Cheng; Yang, Qian; Wang, Si-Wang

2012-01-01

One of the leading causes of death in the world is cerebrovascular disease. Numerous Chinese traditional medicines, such as Cortex Moutan (root bark of Paeonia suffruticosa Andrew) and Radix Salviae miltiorrhizae (root and rhizome of Salvia miltiorrhiza Bunge), protect against cerebrovascular diseases and exhibit anti-atherosclerotic effects. Traditional medicines have been routinely used for a long time in China. In addition, these two herbs are prescribed together in clinical practice. Therefore, the pharmacodynamic interactions between the active constituents of these two herbs, which are paeonol (Pae) and danshensu (DSS), should be particularly studied. The study of Pae and DSS can provide substantial foundations in understanding their mechanisms and empirical evidence to support clinical practice. This study investigated the effects and possible mechanisms of the pharmacodynamic interaction between Pae and DSS on cerebrovascular malfunctioning in diabetes. Experimental diabetes was induced in rats, which was then treated with Pae, DSS, and Pae + DSS for eight weeks. Afterward, cerebral arteries from all groups were isolated and equilibrated in an organ bath with Krebs buffer and ring tension. Effects of Pae, DSS, and Pae + DSS were observed on vessel relaxation with or without endothelium as well as on the basal tonus of vessels from normal and diabetic rats. Indexes about oxidative stress were also determined. We report that the cerebral arteries from diabetic rats show decreased vascular reactivity to acetylcholine (ACh) which was corrected in Pae, DSS, and Pae + DSS treated groups. Furthermore, phenylephrine (PE)-induced contraction response decreased in the treated groups. Phenylephrine and CaCl2-induced vasoconstrictions are partially inhibited in the three treated groups under Ca2+-free medium. Pre-incubated with tetraethylammonium, a non-selective K+ channel blocker, the antagonized relaxation responses increased in DSS and Pae + DSS treated diabetic

The Salt Overly Sensitive (SOS) pathway: established and emerging roles.

PubMed

Ji, Hongtao; Pardo, José M; Batelli, Giorgia; Van Oosten, Michael J; Bressan, Ray A; Li, Xia

2013-03-01

Soil salinity is a growing problem around the world with special relevance in farmlands. The ability to sense and respond to environmental stimuli is among the most fundamental processes that enable plants to survive. At the cellular level, the Salt Overly Sensitive (SOS) signaling pathway that comprises SOS3, SOS2, and SOS1 has been proposed to mediate cellular signaling under salt stress, to maintain ion homeostasis. Less well known is how cellularly heterogenous organs couple the salt signals to homeostasis maintenance of different types of cells and to appropriate growth of the entire organ and plant. Recent evidence strongly indicates that different regulatory mechanisms are adopted by roots and shoots in response to salt stress. Several reports have stated that, in roots, the SOS proteins may have novel roles in addition to their functions in sodium homeostasis. SOS3 plays a critical role in plastic development of lateral roots through modulation of auxin gradients and maxima in roots under mild salt conditions. The SOS proteins also play a role in the dynamics of cytoskeleton under stress. These results imply a high complexity of the regulatory networks involved in plant response to salinity. This review focuses on the emerging complexity of the SOS signaling and SOS protein functions, and highlights recent understanding on how the SOS proteins contribute to different responses to salt stress besides ion homeostasis.

Brown rice and retrograded brown rice alleviate inflammatory response in dextran sulfate sodium (DSS)-induced colitis mice.

PubMed

Praengam, Kemika; Sahasakul, Yuraporn; Kupradinun, Piengchai; Sakarin, Siriwan; Sanitchua, Wanwisa; Rungsipipat, Anudep; Rattanapinyopituk, Kasem; Angkasekwinai, Pornpimon; Changsri, Khaimuk; Mhuantong, Wuttichai; Tangphatsornruang, Sithichoke; Tuntipopipat, Siriporn

2017-12-13

The present study was aimed to investigate the impacts of brown rice (BR) and retrograded brown rice (R-BR) consumption on colonic health and gut microbiota in dextran sulfate sodium (DSS) induced colitis mice. Thirty two female C57Bl/6Mlac mice were fed with modified AIN 93G diets by replacing cornstarch in the original composition with white rice (WR), BR and R-BR powder. The mice were divided into 4 groups and fed with the following experimental diets for 4 weeks: (1) negative control (WR: diet with WR), (2) positive control (DSS_WR: DSS and diet with WR), (3) DSS_BR: DSS and diet with BR, and (4) DSS_R-BR: DSS and diet with R-BR. BR and R-BR had a greater content of fat, dietary fiber, GABA, γ-oryzanol, γ-tocotrienol, ferulic acid and p-coumaric acid than WR (p < 0.05). No significant difference in the level of these bioactive compounds was noted between BR and R-BR. Nevertheless, R-BR had a 1.8 fold resistant starch (RS) content of BR (p < 0.05). The DSS_BR and DSS_R-BR groups showed a lower ratio of colonic weight to length, and a lower content of iNOS, COX-2, MPO, IL-6 and INF-γ in colonic homogenates than the DSS_WR group. However, the DSS treated mice fed with the R-BR diet had significantly milder histopathological inflammatory injury and lower colonic iNOS expression than the DSS_BR and DSS_WR groups. The percentage of mesenteric regulatory T cells significantly increased in the DSS_R-BR group compared to that in the DSS_WR group. The DSS treated mice fed with the R-BR diet showed a significant increase in cecal bacterial diversity and abundance of genera Prevotella, Ruminococcus, Dorea, Coprococcus and Dehalobacterium but a significant decrease in pathogenic bacteria including Bacteroides and Enterococcus compared to the DSS_WR group. Thus, the present data indicate that BR and R-BR ameliorate colonic inflammation in experimental colitis induced by DSS in mice by suppressing inflammatory mediators and modulating regulatory T cell responses as well as

Prevention of salt induced hypertension and fibrosis by angiotensin converting enzyme inhibitors in Dahl S rats

PubMed Central

Liang, B; Leenen, F H H

2007-01-01

Background and purpose: In Dahl S rats, high salt increases activity of the tissue renin-angiotensin-aldosterone system (RAAS) in the CNS, heart and kidneys. Here, we assessed the effects of chronic angiotensin converting enzyme (ACE) inhibition on salt-induced hypertension and cardiovascular and renal hypertrophy and fibrosis, relative to the extent of ACE blockade. Experimental approach: From 4.5 weeks of age, Dahl S rats received either the lipophilic ACE inhibitor trandolapril (1 or 5 mg kg-1 day-1) or the hydrophilic ACE inhibitor lisinopril (10 or 50 mg kg-1 day-1) and a high salt diet was started 0.5 week later. Treatments ended at 9 weeks of age. Key results: High salt diet markedly increased blood pressure (BP), decreased plasma angiotensin II and increased ACE binding densities in brain, heart, aorta and kidneys. Trandolapril and lisinopril prevented 50% of the increase in BP in light and dark period of the day. After the last doses, trandolapril decreased ACE densities by ∼80% in brain nuclei and heart and lisinopril by ∼60% in the brain and by ∼70% in the heart. The two ACE inhibitors prevented right ventricular hypertrophy and attenuated left ventricular hypertrophy but did not affect renal hypertrophy caused by high salt. Both drugs prevented high salt-induced fibrosis in heart, kidney and aorta. Conclusion and implication: As the ACE inhibitors could completely prevent tissue fibrosis and partially prevent tissue hypertrophy and hypertension, the tissue RAAS may play a critical role in salt-induced fibrosis, but a lesser role in the hypertrophy. PMID:17906684

Biochemical Effects of Aqueous Extract of Persea americana (Mill) on the Myocardium of Left Ventricle of High Salt-Fed Adult Wistar Rats.

PubMed

Olushola, Ayoola I; Aderibigbe, Komolafe O; Stephen, Saka O; Ayodeji, Odukoya S

2017-10-01

The cardioprotective effects of Persea americana extract was investigated on biochemical activities of high salt-fed adult Wistar rats in this study. Forty healthy Wistar rats of both sexes weighing 120 to 150 g were randomly assigned into 8 groups of 5 rats each (groups A, B, C, D, E, F, G, and H). Rats in groups A, F, G, and H were fed with standard laboratory pellets, while groups B, C, D, and E were fed on the high-salt diet for 4 weeks. Concomitantly, daily administration of 50, 100, and 150 mg/kg of the P americana extract were given orally to groups C and F, D and G, and E and H, respectively, while rats in groups A and B were administered distilled water. Blood samples were taken by cardiac puncture; concentration of sodium ion, potassium ion, nitric oxide, and activity of lactate dehydrogenase were determined. One-way analysis of variance was used to analyze data, followed by Student-Newman-Keuls (SNK) test for multiple comparison. Results revealed that concentration of potassium ion and nitric oxide was significantly lower ( P < .05) in high salt-fed groups. Sodium ion concentration and activity of lactate dehydrogenase were higher in high salt-fed group while P americana prevented biochemical perturbations in other experimental groups. In conclusion, high salt-diet induced biochemical alterations which were significantly protected by oral administration of P americana extract.

Artificial Intelligence (AI), Operations Research (OR), and Decision Support Systems (DSS): A conceptual framework

NASA Technical Reports Server (NTRS)

Parnell, Gregory S.; Rowell, William F.; Valusek, John R.

1987-01-01

In recent years there has been increasing interest in applying the computer based problem solving techniques of Artificial Intelligence (AI), Operations Research (OR), and Decision Support Systems (DSS) to analyze extremely complex problems. A conceptual framework is developed for successfully integrating these three techniques. First, the fields of AI, OR, and DSS are defined and the relationships among the three fields are explored. Next, a comprehensive adaptive design methodology for AI and OR modeling within the context of a DSS is described. These observations are made: (1) the solution of extremely complex knowledge problems with ill-defined, changing requirements can benefit greatly from the use of the adaptive design process, (2) the field of DSS provides the focus on the decision making process essential for tailoring solutions to these complex problems, (3) the characteristics of AI, OR, and DSS tools appears to be converging rapidly, and (4) there is a growing need for an interdisciplinary AI/OR/DSS education.

Attenuation of cardiac fibrosis by pirfenidone and amiloride in DOCA-salt hypertensive rats

PubMed Central

Mirkovic, Stevo; Seymour, Anne-Marie L; Fenning, Andrew; Strachan, Anna; Margolin, Solomon B; Taylor, Stephen M; Brown, Lindsay

2002-01-01

This study has administered pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone) or amiloride to attenuate the remodelling and associated functional changes, especially an increased cardiac stiffness, in DOCA-salt hypertensive rats. In control rats, the elimination half-life of pirfenidone following a single intravenous dose of 200 mg kg−1 was 37 min while oral bioavailability at this dose was 25.7%. Plasma pirfenidone concentrations in control rats averaged 1.9±0.1 μg ml−1 over 24 h after 14 days' administration as a 0.4% mixture in food. Pirfenidone (approximately 250 – 300 mg kg−1 day−1 as 0.4% in food) and amiloride (1 mg kg−1 day−1 sc) were administered for 2 weeks starting 2 weeks post-surgery. Pirfenidone but not amiloride attenuated ventricular hypertrophy (2.69±0.09, UNX 2.01±0.05. DOCA-salt 3.11±0.09 mg kg−1 body wt) without lowering systolic blood pressure. Collagen deposition was significantly increased in the interstitium after 2 weeks and further increased with scarring of the left ventricle after 4 weeks; pirfenidone and amiloride reversed the increases and prevented further increases. This accumulation of collagen was accompanied by an increase in diastolic stiffness constant; both amiloride and pirfenidone reversed this increase. Noradrenaline potency (positive chronotropy) was decreased in right atria (neg log EC50: control 6.92±0.06; DOCA-salt 6.64±0.08); pirfenidone but not amiloride reversed this change. Noradrenaline was a more potent vasoconstrictor in thoracic aortic rings (neg log EC50: control 6.91±0.10; DOCA-salt 7.90±0.07); pirfenidone treatment did not change noradrenaline potency. Thus, pirfenidone and amiloride reverse and prevent cardiac remodelling and the increased cardiac stiffness without reversing the increased vascular responses to noradrenaline. PMID:11861324

[Correction of isoproterenol-induced myocardial injury with magnesium salts in magnesium-deficient rats].

PubMed

Kharitonova, M V; Zheltova, A A; Spasov, A A; Smirnov, A V; Pan'shin, N G; Iezhitsa, I N

2013-01-01

The effect of Mg L-asparaginate (Mg-L-Asp), Mg chloride (MgCl2) and Mg sulfate (MgSO4) on the severity of isoproterenol-induced myocardial injury in Mg-deficient rats has been evaluated. To induce Mg deficiency, twenty-eight rats were placed on a low Mg diet (Mg content < 15 mg/kg) and demineralized water for 10 weeks. Twelve control rats were fed a basal control diet (Mg content = 500 mg/kg) and water (with Mg content 20 mg/l) for equal duration. On day 49 of low Mg diet, Mg-deficient rats were randomly divided into four groups: 1) group that continued to receive low Mg diet; 2) low Mg diet plus oral MgSO4; 3) low Mg diet plus oral Mg-L-Asp and 4) low Mg diet plus oral MgCl2 (50 mg of Mg per kg of body weight). Isoproterenol was injected subcutaneously (30 mg/kg BW, twice, at an interval of 24 hours) on the day 70 of the study, when plasma and erythrocyte Mg level in rats fed a low Mg diet were significantly decreased by 47% and 45% compared to intact animals. Twenty-four hours after second injection of isoproterenol, tests for activities of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were run and histopathological study was carried out. Administration of isoproterenol to rats resulted in significantly elevated plasma CK, LDH and AST, however analyses in Mg deficient group demonstrated more dramatically increased activity of CK and AST compared to control rats (3,06 and 4,67 fold in Mg-deficient group vs. 1,91 and 3,92 fold in intact group). Increased leakage of cardiac injury markers was concomitant to increased volume of fuchsinophilic cardiomyocytes (54.2 +/- 1.7% in Mg-deficient group and 38.9 +/- 1.9% in intact group, p < 0.05). However, pretreatment with of MgCl2, MgSO4 and Mg-L-Asp during 21 days favorably decreased sensitivity of myocardium to isoproterenol-induced ischemic injury. All evaluated salts significantly decreased myocyte marker enzymes as well as protected myocardium against isoproterenol

Maternal High-Fat and High-Salt Diets Have Differential Programming Effects on Metabolism in Adult Male Rat Offspring.

PubMed

Segovia, Stephanie A; Vickers, Mark H; Harrison, Claudia J; Patel, Rachna; Gray, Clint; Reynolds, Clare M

2018-01-01

Maternal high-fat or high-salt diets can independently program adverse cardiometabolic outcomes in offspring. However, there is a paucity of evidence examining their effects in combination on metabolic function in adult offspring. Female Sprague Dawley rats were randomly assigned to either: control (CD; 10% kcal from fat, 1% NaCl), high-salt (SD; 10% kcal from fat, 4% NaCl), high-fat (HF; 45% kcal from fat, 1% NaCl) or high-fat and salt (HFSD; 45% kcal from fat, 4% NaCl) diets 21 days prior to mating and throughout pregnancy and lactation. Male offspring were weaned onto a standard chow diet and were culled on postnatal day 130 for plasma and tissue collection. Adipocyte histology and adipose tissue, liver, and gut gene expression were examined in adult male offspring. HF offspring had significantly greater body weight, impaired insulin sensitivity and hyperleptinemia compared to CD offspring, but these increases were blunted in HFSD offspring. HF offspring had moderate adipocyte hypertrophy and increased expression of the pre-adipocyte marker Dlk1 . There was a significant effect of maternal salt with increased hepatic expression of Dgat1 and Igfb2 . Gut expression of inflammatory ( Il1r1, Tnfα, Il6 , and Il6r ) and renin-angiotensin system ( Agtr1a, Agtr1b ) markers was significantly reduced in HFSD offspring compared to HF offspring. Therefore, salt mitigates some adverse offspring outcomes associated with a maternal HF diet, which may be mediated by altered adipose tissue morphology and gut inflammatory and renin-angiotensin regulation.

Parasympathetic activation by pyridostigmine on chemoreflex sensitivity in heart-failure rats.

PubMed

Sabino, João Paulo J; da Silva, Carlos Alberto Aguiar; Giusti, Humberto; Glass, Mogens Lesner; Salgado, Helio C; Fazan, Rubens

2013-12-01

We evaluated the effects of parasympathetic activation by pyridostigmine (PYR) on chemoreflex sensitivity in a rat model of heart failure (HF rats). HF rats demonstrated higher pulmonary ventilation (PV), which was not affected by PYR. When HF and control rats treated or untreated with PYR were exposed to 15% O2, all groups exhibited prompt increases in respiratory frequency (RF), tidal volume (TV) and PV. When HF rats were exposed to 10% O2 they showed greater PV response which was prevented by PYR. The hypercapnia triggered by either 5% CO2 or 10% CO2 promoted greater RF and PV responses in HF rats. PYR blunted the RF response in HF rats but did not affect the PV response. In conclusion, PYR prevented increased peripheral chemoreflex sensitivity, partially blunted central chemoreflex sensitivity and did not affect basal PV in HF rats. © 2013.

Hydrologic Drought Decision Support System (HyDroDSS)

USGS Publications Warehouse

Granato, Gregory E.

2014-01-01

The hydrologic drought decision support system (HyDroDSS) was developed by the U.S. Geological Survey (USGS) in cooperation with the Rhode Island Water Resources Board (RIWRB) for use in the analysis of hydrologic variables that may indicate the risk for streamflows to be below user-defined flow targets at a designated site of interest, which is defined herein as data-collection site on a stream that may be adversely affected by pumping. Hydrologic drought is defined for this study as a period of lower than normal streamflows caused by precipitation deficits and (or) water withdrawals. The HyDroDSS is designed to provide water managers with risk-based information for balancing water-supply needs and aquatic-habitat protection goals to mitigate potential effects of hydrologic drought. This report describes the theory and methods for retrospective streamflow-depletion analysis, rank correlation analysis, and drought-projection analysis. All three methods are designed to inform decisions made by drought steering committees and decisionmakers on the basis of quantitative risk assessment. All three methods use estimates of unaltered streamflow, which is the measured or modeled flow without major withdrawals or discharges, to approximate a natural low-flow regime. Retrospective streamflow-depletion analysis can be used by water-resource managers to evaluate relations between withdrawal plans and the potential effects of withdrawal plans on streams at one or more sites of interest in an area. Retrospective streamflow-depletion analysis indicates the historical risk of being below user-defined flow targets if different pumping plans were implemented for the period of record. Retrospective streamflow-depletion analysis also indicates the risk for creating hydrologic drought conditions caused by use of a pumping plan. Retrospective streamflow-depletion analysis is done by calculating the net streamflow depletions from withdrawals and discharges and applying these depletions

Role of the Vascular Wall in Sodium Homeostasis and Salt Sensitivity

PubMed Central

Olde Engberink, Rik H.G.; Rorije, Nienke M.G.; Homan van der Heide, Jaap J.; van den Born, Bert-Jan H.

2015-01-01

Excessive sodium intake is associated with both hypertension and an increased risk of cardiovascular events, presumably because of an increase in extracellular volume. The extent to which sodium intake affects extracellular volume and BP varies considerably among individuals, discriminating subjects who are salt-sensitive from those who are salt-resistant. Recent experiments have shown that, other than regulation by the kidney, sodium homeostasis is also regulated by negatively charged glycosaminoglycans in the skin interstitium, where sodium is bound to glycosaminoglycans without commensurate effects on extracellular volume. The endothelial surface layer is a dynamic layer on the luminal side of the endothelium that is in continuous exchange with flowing blood. Because negatively charged glycosaminoglycans are abundantly present in this layer, it may act as an intravascular buffer compartment that allows sodium to be transiently stored. This review focuses on the putative role of the endothelial surface layer as a contributor to salt sensitivity, the consequences of a perturbed endothelial surface layer on sodium homeostasis, and the endothelial surface layer as a possible target for the treatment of hypertension and an expanded extracellular volume. PMID:25294232

Renal tubular angiotensin converting enzyme is responsible for nitro-L-arginine methyl ester (L-NAME)-induced salt sensitivity

PubMed Central

Giani, Jorge F.; Eriguchi, Masahiro; Bernstein, Ellen A.; Katsumata, Makoto; Shen, Xiao Z.; Li, Liang; McDonough, Alicia A.; Fuchs, Sebastien; Bernstein, Kenneth E.; Gonzalez-Villalobos, Romer A.

2017-01-01

Renal parenchymal injury predisposes to salt-sensitive hypertension, but how this occurs is not known. Here we tested whether renal tubular angiotensin converting enzyme (ACE), the main site of kidney ACE expression, is central to the development of salt sensitivity in this setting. Two mouse models were used: it-ACE mice in which ACE expression is selectively eliminated from renal tubular epithelial cells; and ACE 3/9 mice, a compound heterozygous mouse model that makes ACE only in renal tubular epithelium from the ACE 9 allele, and in liver hepatocytes from the ACE 3 allele. Salt sensitivity was induced using a post L-NAME salt challenge. While both wild-type and ACE 3/9 mice developed arterial hypertension following three weeks of high salt administration, it-ACE mice remained normotensive with low levels of renal angiotensin II. These mice displayed increased sodium excretion, lower sodium accumulation, and an exaggerated reduction in distal sodium transporters. Thus, in mice with renal injury induced by L-NAME pretreatment, renal tubular epithelial ACE, and not ACE expression by renal endothelium, lung, brain, or plasma, is essential for renal angiotensin II accumulation and salt-sensitive hypertension. PMID:27988209

DSS 13 microprocessor antenna controller

NASA Technical Reports Server (NTRS)

Gosline, R. M.

1988-01-01

A microprocessor-based antenna monitor and control system with multiple CPUs are described. The system was developed as part of the unattended station project for DSS 13 and was enhanced for use by the SETI project. The operational features, hardware, and software designs are described, and a discussion is provided of the major problems encountered.

Renal neural mechanisms in salt-sensitive hypertension.

PubMed

DiBona, G F

1995-01-01

Genetic forms of salt (NaCl)-sensitive hypertension are characterized by increased renal sympathetic nerve activity responses to environmental stimuli. The increases in renal sympathetic nerve activity produce marked changes in renal function with renal vasoconstriction and sodium and water retention which can contribute to the initiation, development and maintenance of hypertension. In genetic forms of NaCl-sensitive hypertension, increased dietary NaCl intake produces alterations in norepinephrine kinetics with decreased concentrations of norepinephrine in regions of the anterior hypothalamus which are critical for the regulation of peripheral sympathetic nerve activity. This local central decrease in tonic alpha 2 adrenoceptor sympathoinhibitory input leads to increased peripheral (renal) sympathetic nerve activity and hypertension. Similarly, with increased dietary NaCl intake, patients with NaCl-sensitive hypertension develop increased arterial pressure, renal vasoconstriction, increased glomerular capillary pressure and increased urinary albumin excretion. Thus, increased dietary NaCl intake can, via central nervous system actions, produce increases in renal sympathetic nerve activity whose renal functional effects contribute to the pathophysiology of hypertension.

Salt-sparing diuretic action of a water-soluble urea analog inhibitor of urea transporters UT-A and UT-B in rats

PubMed Central

Cil, Onur; Esteva-Font, Cristina; Tas, Sadik Taskin; Su, Tao; Lee, Sujin; Anderson, Marc O.; Ertunc, Mert; Verkman, A. S.

2015-01-01

Inhibitors of kidney urea transporter (UT) proteins have potential use as salt-sparing diuretics (‘urearetics’) with a different mechanism of action than diuretics that target salt transporters. To study UT inhibition in rats, we screened about 10,000 drugs, natural products and urea analogs for inhibition of rat UT-A1. Drug and natural product screening found nicotine, sanguinarine and an indolcarbonylchromenone with IC50 of 10–20 μM. Urea analog screening found methylacetamide and dimethylthiourea (DMTU). DMTU fully and reversibly inhibited rat UT-A1 and UT-B by a noncompetitive mechanism with IC50 of 2–3 mM. Homology modeling and docking computations suggested DMTU binding sites on rat UT-A1. Following a single intraperitoneal injection of 500 mg/kg DMTU, peak plasma concentration was 9 mM with t1/2 of about 10 hours, and a urine concentration of 20–40 mM. Rats chronically treated with DMTU had a sustained, reversible reduction in urine osmolality from 1800 to 600 mOsm, a 3-fold increase in urine output, and mild hypokalemia. DMTU did not impair urinary concentrating function in rats on a low protein diet. Compared to furosemide-treated rats, the DMTU-treated rats had greater diuresis and reduced urinary salt loss. In a model of Syndrome of Inappropriate Antidiuretic Hormone secretion, DMTU treatment prevented hyponatremia and water retention produced by water-loading in dDAVP-treated rats. Thus, our results establish a rat model of UT inhibition and demonstrate the diuretic efficacy of UT inhibition. PMID:25993324

Salt-sparing diuretic action of a water-soluble urea analog inhibitor of urea transporters UT-A and UT-B in rats.

PubMed

Cil, Onur; Esteva-Font, Cristina; Tas, Sadik Taskin; Su, Tao; Lee, Sujin; Anderson, Marc O; Ertunc, Mert; Verkman, Alan S

2015-08-01

Inhibitors of kidney urea transporter (UT) proteins have potential use as salt-sparing diuretics ('urearetics') with a different mechanism of action than diuretics that target salt transporters. To study UT inhibition in rats, we screened about 10,000 drugs, natural products and urea analogs for inhibition of rat UT-A1. Drug and natural product screening found nicotine, sanguinarine and an indolcarbonylchromenone with IC50 of 10-20 μM. Urea analog screening found methylacetamide and dimethylthiourea (DMTU). DMTU fully and reversibly inhibited rat UT-A1 and UT-B by a noncompetitive mechanism with IC50 of 2-3 mM. Homology modeling and docking computations suggested DMTU binding sites on rat UT-A1. Following a single intraperitoneal injection of 500 mg/kg DMTU, peak plasma concentration was 9 mM with t1/2 of about 10 h, and a urine concentration of 20-40 mM. Rats chronically treated with DMTU had a sustained, reversible reduction in urine osmolality from 1800 to 600 mOsm, a 3-fold increase in urine output, and mild hypokalemia. DMTU did not impair urinary concentrating function in rats on a low protein diet. Compared to furosemide-treated rats, the DMTU-treated rats had greater diuresis and reduced urinary salt loss. In a model of syndrome of inappropriate antidiuretic hormone secretion, DMTU treatment prevented hyponatremia and water retention produced by water-loading in dDAVP-treated rats. Thus, our results establish a rat model of UT inhibition and demonstrate the diuretic efficacy of UT inhibition.

Protective effect of dietary potassium against cardiovascular damage in salt-sensitive hypertension: possible role of its antioxidant action.

PubMed

Ando, Katsuyuki; Matsui, Hiromitsu; Fujita, Megumi; Fujita, Toshiro

2010-01-01

It is well known that high salt intake induces hypertension and cardiovascular damage, while dietary potassium supplementation counteracts these harmful effects. Actually, the protective effect of potassium is strengthened with excess salt as compared with salt depletion. Although the precise mechanisms have not been fully elucidated, in our previous reports, the antihypertensive effect of dietary potassium was accompanied by sympathetic nerve inhibition in salt-sensitive hypertension. Also, potassium supplement suppressed salt-induced insulin resistance. These effects of dietary potassium can explain its cardio- and vasculo-protective action in addition to the potassium supplementation induced decreased salt-induced rise in blood pressure. On the other hand, salt-sensitive hypertension is associated with reactive oxygen species (ROS) overproduction. Moreover, sympathoexcitation can be induced by central ROS upregulation and insulin resistance can be caused by ROS excess in the target organs of insulin, such as skeletal muscle. Conversely, the seemingly different actions of potassium can be explained by the antioxidant effect of dietary potassium; in our recent studies, potassium supplementation inhibits salt-induced progress of cardiac diastolic dysfunction and vascular neointima formation by cuff placement around arteries, associated with the inhibition of regional ROS overproduction, in salt-sensitive hypertension. Thus, it is possible that dietary potassium protects against salt-induced cardiovascular damage by the reduction of ROS generation and by central sympatholytic action and amelioration of insulin resistance induced through its antioxidant effect.

The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

PubMed

Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

2016-02-01

A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes. © 2016 John Wiley & Sons Australia, Ltd.

32 CFR 321.14 - DSS implementation policies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... to all sources of investigative information, including subjects, during interview, in response to questions that go beyond the required printed and oral notices. Agents shall be guided by DSS Handbook for...

32 CFR 321.14 - DSS implementation policies.

Code of Federal Regulations, 2011 CFR

2011-07-01

... to all sources of investigative information, including subjects, during interview, in response to questions that go beyond the required printed and oral notices. Agents shall be guided by DSS Handbook for...

HRMS sky survey wideband feed system design for DSS 24 beam waveguide antenna

NASA Technical Reports Server (NTRS)

Stanton, P. H.; Lee, P. R.; Reilly, H. F.

1993-01-01

The High-Resolution Microwave Survey (HRMS) Sky Survey project will be implemented on the DSS 24 beam waveguide (BWG) antenna over the frequency range of 2.86 to 10 GHz. Two wideband, ring-loaded, corrugated feed horns were designed to cover this range. The horns match the frequency-dependent gain requirements for the DSS 24 BWG system. The performance of the feed horns and the calculated system performance of DSS 24 are presented.

Promotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry.

PubMed

Zhao, Weixing; Vaithiyalingam, Sivaraja; San Filippo, Joseph; Maranon, David G; Jimenez-Sainz, Judit; Fontenay, Gerald V; Kwon, Youngho; Leung, Stanley G; Lu, Lucy; Jensen, Ryan B; Chazin, Walter J; Wiese, Claudia; Sung, Patrick

2015-07-16

The tumor suppressor BRCA2 is thought to facilitate the handoff of ssDNA from replication protein A (RPA) to the RAD51 recombinase during DNA break and replication fork repair by homologous recombination. However, we find that RPA-RAD51 exchange requires the BRCA2 partner DSS1. Biochemical, structural, and in vivo analyses reveal that DSS1 allows the BRCA2-DSS1 complex to physically and functionally interact with RPA. Mechanistically, DSS1 acts as a DNA mimic to attenuate the affinity of RPA for ssDNA. A mutation in the solvent-exposed acidic domain of DSS1 compromises the efficacy of RPA-RAD51 exchange. Thus, by targeting RPA and mimicking DNA, DSS1 functions with BRCA2 in a two-component homologous recombination mediator complex in genome maintenance and tumor suppression. Our findings may provide a paradigm for understanding the roles of DSS1 in other biological processes. Copyright © 2015 Elsevier Inc. All rights reserved.

WAR DSS: A DECISION SUPPORT SYSTEM FOR ENVIRONMENTALLY CONSCIOUS CHEMICAL PROCESS DESIGN

EPA Science Inventory

The second generation of the Waste Reduction (WAR) Algorithm is constructed as a decision support system (DSS) in the design of chemical manufacturing facilities. The WAR DSS is a software tool that can help reduce the potential environmental impacts (PEIs) of industrial chemical...

Sensitivity of storage field performance to geologic and cavern design parameters in salt domes.

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

Ehgartner, Brian L.; Park, Byoung Yoon

2009-03-01

A sensitivity study was performed utilizing a three dimensional finite element model to assess allowable cavern field sizes for strategic petroleum reserve salt domes. A potential exists for tensile fracturing and dilatancy damage to salt that can compromise the integrity of a cavern field in situations where high extraction ratios exist. The effects of salt creep rate, depth of salt dome top, dome size, caprock thickness, elastic moduli of caprock and surrounding rock, lateral stress ratio of surrounding rock, cavern size, depth of cavern, and number of caverns are examined numerically. As a result, a correlation table between the parametersmore » and the impact on the performance of storage field was established. In general, slower salt creep rates, deeper depth of salt dome top, larger elastic moduli of caprock and surrounding rock, and a smaller radius of cavern are better for structural performance of the salt dome.« less

Long-Term Inhibition of Xanthine Oxidase by Febuxostat Does Not Decrease Blood Pressure in Deoxycorticosterone Acetate (DOCA)-Salt Hypertensive Rats

PubMed Central

Szasz, Theodora; Davis, Robert Patrick; Garver, Hannah S.; Burnett, Robert J.; Fink, Gregory D.; Watts, Stephanie W.

2013-01-01

Xanthine oxidase and its products, uric acid and ROS, have been implicated in the pathogenesis of cardiovascular disease, such as hypertension. We have previously reported that allopurinol inhibition of XO does not alter the progression of deoxycorticosterone acetate (DOCA)-salt hypertension in rats. However other researchers have observed a reduction in blood pressure after allopurinol treatment in the same model. To resolve this controversy, in this study we used the newer and more effective XO inhibitor febuxostat, and hypothesized that a more complete XO blockade might impair hypertension development and its end-organ consequences. We used DOCA-salt hypertensive rats and administered vehicle (salt water) or febuxostat (orally, 5 mg/kg/day in salt water) in a short-term “reversal” experiment (2 weeks of treatment 3 weeks after DOCA-salt beginning) and a long-term “prevention” experiment (treatment throughout 4 weeks of DOCA-salt). We confirmed XO inhibition by febuxostat by measuring circulating and tissue levels of XO metabolites. We found an overall increase in hypoxanthine (XO substrate) and decrease in uric acid (XO product) levels following febuxostat treatment. However, despite a trend for reduced blood pressure in the last week of long-term febuxostat treatment, no statistically significant difference in hemodynamic parameters was observed in either study. Additionally, no change was observed in relative heart and kidney weight. Aortic media/lumen ratio was minimally improved by long-term febuxostat treatment. Additionally, febuxostat incubation in vitro did not modify contraction of aorta or vena cava to norepinephrine, angiotensin II or endothelin-1. We conclude that XO inhibition is insufficient to attenuate hypertension in the rat DOCA-salt model, although beneficial vascular effects are possible. PMID:23393607

Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

PubMed

Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

2015-10-10

Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. Copyright © 2015 Elsevier B.V. All rights reserved.

CD8+ T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension.

PubMed

Liu, Yunmeng; Rafferty, Tonya M; Rhee, Sung W; Webber, Jessica S; Song, Li; Ko, Benjamin; Hoover, Robert S; He, Beixiang; Mu, Shengyu

2017-01-09

Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8 + T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8 + T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8 + T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K + channel Kir4.1, and stimulation of the Cl - channel ClC-K. The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension.

CD8+ T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension

PubMed Central

Liu, Yunmeng; Rafferty, Tonya M.; Rhee, Sung W.; Webber, Jessica S.; Song, Li; Ko, Benjamin; Hoover, Robert S.; He, Beixiang; Mu, Shengyu

2017-01-01

Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8+ T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8+ T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension. Co-culture with CD8+ T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K+ channel Kir4.1, and stimulation of the Cl− channel ClC-K. The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention. Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension. PMID:28067240

Modeling and analysis of the DSS-14 antenna control system

NASA Technical Reports Server (NTRS)

Gawronski, W.; Bartos, R.

1996-01-01

An improvement of pointing precision of the DSS-14 antenna is planned for the near future. In order to analyze the improvement limits and to design new controllers, a precise model of the antenna and the servo is developed, including a finite element model of the antenna structure and detailed models of the hydraulic drives and electronic parts. The DSS-14 antenna control system has two modes of operation: computer mode and precision mode. The principal goal of this investigation is to develop the model of the computer mode and to evaluate its performance. The DSS-14 antenna computer model consists of the antenna structure and drives in azimuth and elevation. For this model, the position servo loop is derived, and simulations of the closed-loop antenna dynamics are presented. The model is significantly different from that for the 34-m beam-waveguide antennas.

RF optics study for DSS-43 ultracone implementation

NASA Technical Reports Server (NTRS)

Lee, P.; Veruttipong, W.

1994-01-01

The Ultracone feed system will be implemented on DSS 43 to support the S-band (2.3 GHz) Galileo contingency mission. The feed system will be installed in the host country's cone, which is normally used for radio astronomy, VLBI, and holography. The design must retain existing radio-astronomy capabilities, which could be impaired by shadowing from the large S-band feed horn. Computer calculations were completed to estimate system performance and shadowing effects for various configurations of the host country's cone feed systems. Also, the DSS-43 system performance using higher gain S-band horns was analyzed. A new S-band horn design with improved return loss and cross-polarization characteristics is presented.

Pharmacokinetic alterations of rhubarb anthraquinones in experimental colitis induced by dextran sulfate sodium in the rat.

PubMed

Wu, Wen-Jin; Yan, Ru; Li, Ting; Li, Ya-Ping; Zhou, Rui-Na; Wang, Yi-Tao

2017-02-23

Rhubarb (Rhei Rhizoma et Radix) is used for the treatment of digestive diseases in traditional medicinal practice in China. Recent studies also support its beneficial activities in alleviating ulcerative colitis (UC). This study aimed to characterize the oral pharmacokinetics of rhubarb anthraquinones, the main bioactive components of this herb, in the experimental chronic colitis rat model induced by dextran sulfate sodium (DSS) and to identify the factors causing the pharmacokinetic alterations. Rats received drinking water (normal group) or 5% DSS for the first 7 days and 3% DSS for additional 14 days (UC group). On day 21 both groups received an oral dose of the rhubarb extract (equivalent to 5.0g crude drug/kg body weight). Plasma anthraquinone aglycones levels were determined directly by an LC-MS/MS method and the total of each anthraquinone (aglycone+conjugates) was quantified after β-glucuronidases hydrolysis. Rhubarb anthraquinones predominantly existed as conjugates in plasma samples from both groups and only free aloe-emodin, rhein and emodin were detected. Compared to the normal rats, both C max and AUC of the three free anthraquinones were increased, while the systemic exposure (AUC) of the total (aglycone+conjugates) of most anthraquinones decreased by UC accompanied by the disappearance of multiple-peak phenomenon in the plasma concentration-time profiles. Gut bacteria from UC rats exhibited a decreased activity in hydrolyzing anthraquinone glycosides to form respective aglycone and there were significant decreases in microbial β-glucosidases and β-glucuronidases activities. Moreover, the intestinal microsomes from UC rats catalyzed glucuronidation of free anthraquinones with higher activities, while the activities of hepatic microsomes were comparable to normal rats. The decreases of β-glucuronidases activity in DSS-induced chronic rat colitis should mainly account for the decreases in systemic exposure and abrogation of enterohepatic

Evaluation of a rapid protocol for the assessment of salt sensitivity against the blood pressure response to dietary sodium chloride restriction.

PubMed

Galletti, F; Ferrara, I; Stinga, F; Iacone, R; Noviello, F; Strazzullo, P

1997-04-01

The "gold standard" for the assessment of salt sensitivity of hypertension is the blood pressure response to dietary NaCl restriction; nevertheless, for practical purposes, a more rapid test that would not depend on the patient's compliance to the dietary prescription would be very useful in clinical research and medical practice. The aim of this study was thus to evaluate the effectiveness and reliability of a rapid, easy-to-standardize protocol for the assessment of salt sensitivity against the blood pressure response to dietary salt restriction. A total of 108 hypertensive patients were screened for salt sensitivity by the modified protocol of Grim et al. Thereafter, nine patients identified by the test as salt sensitive and nine identified as salt resistant followed, for two consecutive periods of 1 week, a diet with normal (200 mmol/day) or low (50 mmol/day) NaCl content. Compliance to the diet was checked by repeated 24-h urine collections. The group as a whole experienced a significant fall in blood pressure during the low Na diet (mean pressure = 123 +/- 3 v 118 +/- 3 mm Hg; P < .05). However, whereas patients identified as salt sensitive by the Grim protocol had a marked and significant blood pressure decrease (systolic -12 mm Hg, diastolic -7 mm Hg), no change was observed in those classified as salt resistant (systolic -2 mm Hg, diastolic -2 mm Hg). A significant correlation between changes in urinary Na excretion and changes in blood pressure was found only in salt-sensitive hypertensive patients. In conclusion, the modified Grim protocol tested in this study was able to correctly predict a significant blood pressure response to dietary salt restriction in the majority of cases. A validation of this test in a larger patient population may be advisable.

Airway extravasation induced by increasing airway temperature in ovalbumin-sensitized rats

PubMed Central

Hsu, Chun-Chun; Tapia, Reyno J.; Lee, Lu-Yuan

2015-01-01

This study was carried out to determine whether hyperventilation of humidified warm air (HWA) induced airway extravasation in ovalbumin (Ova)-sensitized rats. Our results showed: 1) After isocapnic hyperventilation with HWA for 2 min, tracheal temperature (Ttr) was increased to 40.3°C, and the Evans blue contents in major airways and lung tissue were elevated to 651% and 707%, respectively, of that after hyperventilation with humidified room air in Ova-sensitized rats; this striking effect of HWA was absent in control rats. 2) The HWA-induced increase in Evans blue content in sensitized rats was completely prevented by a pretreatment with either L-732138, a selective antagonist of neurokinin type 1 (NK-1) receptor, or formoterol, a selective agonist of β2 adrenoceptor. This study demonstrated that an increase in airway temperature induced protein extravasation in the major airways and lung tissue of sensitized rats, and an activation of the NK-1 receptor by tachykinins released from bronchopulmonary C-fiber nerve endings was primarily responsible. PMID:25864799

A Novel Modification of the AOM/DSS Model for Inducing Intestinal Adenomas in Mice.

PubMed

Angelou, Anastasios; Andreatos, Nikolaos; Antoniou, Efstathios; Zacharioudaki, Argiro; Theodoropoulos, George; Damaskos, Christos; Garmpis, Nikolaos; Yuan, Chunhui; Xiao, Weidong; Theocharis, Stamatios; Zografos, George; Papalois, Apostolos; Margonis, Georgios Antonios

2018-06-01

Our aim was to develop an animal model of the precancerous stages of colitis-associated carcinogenesis by modifying the established azoxymethane/dextran sulfate sodium (AOM/DSS) protocol. Six mice were treated with varying cycles of DSS following AOM administration as above (group 1: three mice received three 5-day cycles of 3.0% DSS and group 2: three mice received three 7-day cycles of 2.5% DSS; every cycle was followed by a 2-week rest period) and were sacrificed on day 84 of the experiment. By contrast, three female C57BL6 mice (group 3) were treated with a single intraperitoneal dose (10 mg/kg of body weight) of AOM followed by three 5-day cycles of oral 2.5% DSS, with each cycle interrupted by a 2-week rest period. The mice of this group were sacrificed at 60 days. In groups 1 and 2, cancer was noted in five out of the six mice. In group 3, adenomas with dysplastic lesions were noted in all of the mice, but none had developed adenocarcinoma. Our results suggest that the administration of three 5-day cycles of 2.5% DSS following an initial dose of AOM may successfully induce adenoma formation without the concurrent presence of carcinoma in female C57BL6 mice that are sacrificed on experimental day 60. In turn, this modification of the widely used AOM/DSS protocol may constitute a novel approach for investigating colitis-related colonic adenomas. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Role of PDGFs/PDGFRs signaling pathway in myocardial fibrosis of DOCA/salt hypertensive rats

PubMed Central

Fan, Bin; Ma, Likun; Li, Qian; Wang, Lin; Zhou, Junling; Wu, Jiawei

2014-01-01

This study aimed to investigate the role of PDGF/PDGFR signaling pathway in myocardial fibrosis of desoxycorticosterone (DOCA) induced salt-sensitive hypertensive rats and explore the influence of PDGF/PDGFR signaling pathway on fibroblasts and myofibroblasts in the heart. 60 male SD rats underwent right nephrectomy and bred with 1% sodium chloride and 0.1% potassium chloride for 4 weeks, and then randomly divided into 3 groups (CON group, DOCA group and DOCA+IMA group). Results showed that: 1) 14 and 28 days after intervention, the SBP in DOCA and DOCA+IMA group was significantly higher than that in CON group. At days 28, the severity of myocardial fibrosis and PVCA/VA ratio in DOCA group were significantly increased when compared with CON group. The severity of myocardial fibrosis and PVCA/VA ratio in DOCA+IMA group were markedly lower than those in DOCA group although they were higher than those in CON group. 2) At days 14, the mRNA expressions of PDGFRα and PDGFRβ in DOCA group were significantly higher than CON and DOCA+IMA group. At days 28, the mRNA expressions of PDGFRβ, FSP-1, α-SMA, procollagen I and procollagen III in DOCA group were significantly higher than those in CON group. In addition, in a specific group, the PDGFRβ mRNA expression was higher than the PDGFRα mRNA expression. In DOCA+IMA group, the mRNA expressions of PDGFRβ, FSP-1, α-SMA, procollagen I and procollagen III were markedly reduced when compared with DOCA group. 3) At 14 days, the protein expressions of PDGFRα and PDGFRβ in DOCA group were significantly higher than those in CON group. The PDGFRα protein expression in DOCA+IMA group was markedly lower than that in DOCA group. At days 28, the protein expressions of PDGFRα and PDGFRβ in DOCA group were significantly increased when compared with CON group. The protein expressions of PDGFRα and PDGFRβ in DOCA+IMA group were significantly lower than those in DOCA group. At day 28, the cardiac interstitium mainly contained

Effect of excess dietary salt on calcium metabolism and bone mineral in a spaceflight rat model

NASA Technical Reports Server (NTRS)

Navidi, Meena; Wolinsky, Ira; Fung, Paul; Arnaud, Sara B.

1995-01-01

High levels of salt promote urinary calcium (UCa) loss and have the potential to cause bone mineral deficits if intestinal Ca absorption does not compensate for these losses. To determine the effect of excess dietary salt on the osteopenia that follows skeletal unloading, we used a spaceflight model that unloads the hindlimbs of 200-g rats by tail suspension (S). Rats were studied for 2 wk on diets containing high salt (4 and 8%) and normal calcium (0.45%) and for 4 wk on diets containing 8% salt (HiNa) and 0.2% Ca (LoCa). Final body weights were 9-11% lower in S than in control rats (C) in both experiments, reflecting lower growth rates in S than in C during pair feeding. UCa represented 12% of dietary Ca on HiNA diets and was twofold higher in S than in C transiently during unloading. Net intestinal Ca absorption was consistently 11-18% lower in S than in C. Serum 1,25-dihydroxyvitamin D was unaffected by either LoCa or HiNa diets in S but was increased by LoCa and HiNa diets in C. Despite depressed intestinal Ca absoption in S and a sluggish response of the Ca endocrine system to HiNa diets, UCa loss did not appear to affect the osteopenia induced by unloading. Although any deficit in bone mineral content from HiNa diets may have been too small to detect or the duration of the study too short to manifest, there were clear differences in Ca metabolism from control levels in the response of the spaceflight model to HiNa diets, indicated by depression of intestinal Ca absorption and its regulatory hormone.

Effect of cyclodextrin complexation of curcumin on its solubility and antiangiogenic and anti-inflammatory activity in rat colitis model.

PubMed

Yadav, Vivek R; Suresh, Sarasija; Devi, Kshama; Yadav, Seema

2009-01-01

The purpose of the study was to prepare and evaluate the anti-inflammatory activity of cyclodextrin (CD) complex of curcumin for the treatment of inflammatory bowel disease (IBD) in colitis-induced rat model. Inclusion complexes of curcumin were prepared by common solvent and kneading methods. These complexes were further evaluated for increase in solubility of poorly soluble curcumin. The inclusion complexes were characterized for enhancement in solubility, in vitro dissolution, surface morphology, infrared, differential scanning calorimetry, and X-ray studies. Solubility, phase solubility, and in vitro dissolution studies showed that curcumin has higher affinity for hydroxypropyl-beta-CD (HPbetaCD) than other CDs. HPbetaCD complex of curcumin was further investigated for its antiangiogenic and anti-inflammatory activity using chick embryo and rat colitis model. HPbetaCD complex of curcumin proved to be a potent angioinhibitory compound, as demonstrated by inhibition of angiogenesis in chorioallantoic membrane assay. Curcumin- and HPbetaCD-treated rats showed a faster weight gain compared to dextran sulfate solution (DSS) controls. Whole colon length appeared to be significantly longer in HPbetaCD-treated rats than pure curcumin and DSS controls. An additional finding in the DSS-treated rats was the predominance of eosinophils in the chronic cell infiltrate. Decreased mast cell numbers in the mucosa of the colon of CD of curcumin- and pure-curcumin-treated rats was observed. This study concluded that the degree of colitis caused by administration of DSS was significantly attenuated by CD of curcumin. Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for IBD patients.

Isolated Flinders Sensitive Line rats have decreased dopamine D2 receptor mRNA.

PubMed

Bjørnebekk, Astrid; Mathé, Aleksander A; Brené, Stefan

2007-07-02

Social isolation has profound effects on animal behavior and dopamine systems. We investigated the effect of social isolation on the dopamine receptor and neuropeptide mRNAs in the brain reward system in an animal model of depression, the Flinders Sensitive Line rats and Sprague-Dawley controls. We demonstrate that socially isolated but not group housed Flinders sensitive line rats had lower dopamine D2 receptor mRNA levels compared with Sprague-Dawley rats. Isolated and group housed Flinders Sensitive Line rats had higher levels of dopamine D1 receptor and substance P and enkephalin but not dynorphin mRNAs when compared with Sprague-Dawley rats. Our findings of decreased dopamine D2 receptor levels in socially isolated Flinders Sensitive Line rats suggest that low D2 receptor expression may play a role in pathophysiology of depression.

Altered potassium ATP channel signaling in mesenteric arteries of old high salt-fed rats

PubMed Central

Whidden, Melissa A.; Basgut, Bilgen; Kirichenko, Nataliya; Erdos, Benedek; Tümer, Nihal

2016-01-01

[Purpose] Both aging and the consumption of a high salt diet are associated with clear changes in the vascular system that can lead to the development of cardiovascular disease; however the mechanisms are not clearly understood. Therefore, we examined whether aging and the consumption of excess salt alters the function of potassium ATP-dependent channel signaling in mesenteric arteries [Methods] Young (7 months) and old (29 months) Fischer 344 x Brown Norway rats were fed a control or a high salt diet (8% NaCl) for 12 days and mesenteric arteries were utilized for vascular reactivity measurements. [Results] Acetylcholine-induced endothelium relaxation was significantly reduced in old arteries (81 ± 4%) when compared with young arteries (92 ± 2%). Pretreatment with the potassium-ATP channel blocker glibenclamide reduced relaxation to acetylcholine in young arteries but did not alter dilation in old arteries. On a high salt diet, endothelium dilation to acetylcholine was significantly reduced in old salt arteries (60 ± 3%) when compared with old control arteries (81 ± 4%). Glibenclamide reduced acetylcholine-induced dilation in young salt arteries but had no effect on old salt arteries. Dilation to cromakalim, a potassium-ATP channel opener, was reduced in old salt arteries when compared with old control arteries. [Conclusion] These findings demonstrate that aging impairs endothelium-dependent relaxation in mesenteric arteries. Furthermore, a high salt diet alters the function of potassium-ATP-dependent channel signaling in old isolated mesenteric arteries and affects the mediation of relaxation stimuli. PMID:27508155

Blockade of renal medullary bradykinin B2 receptors increases tubular sodium reabsorption in rats fed a normal-salt diet

PubMed Central

Sivritas, Sema-Hayriye; Ploth, David W.; Fitzgibbon, Wayne R.

2008-01-01

The present study was performed to test the hypothesis that under normal physiological conditions and/or during augmentation of kinin levels, intrarenal kinins act on medullary bradykinin B2 (BKB2) receptors to acutely increase papillary blood flow (PBF) and therefore Na+ excretion. We determined the effect of acute inner medullary interstitial (IMI) BKB2 receptor blockade on renal hemodynamics and excretory function in rats fed either a normal (0.23%)- or a low (0.08%)-NaCl diet. For each NaCl diet, two groups of rats were studied. Baseline renal hemodynamic and excretory function were determined during IMI infusion of 0.9% NaCl into the left kidney. The infusion was then either changed to HOE-140 (100 μg·kg−1·h−1, treated group) or maintained with 0.9% NaCl (time control group), and the parameters were again determined. In rats fed a normal-salt diet, HOE-140 infusion decreased left kidney Na+ excretion (urinary Na+ extraction rate) and fractional Na+ excretion by 40 ± 5% and 40 ± 4%, respectively (P < 0.01), but did not alter glomerular filtration rate, inner medullary blood flow (PBF), or cortical blood flow. In rats fed a low-salt diet, HOE-140 infusion did not alter renal regional hemodynamics or excretory function. We conclude that in rats fed a normal-salt diet, kinins act tonically via medullary BKB2 receptors to increase Na+ excretion independent of changes in inner medullary blood flow. PMID:18632797

The logic of selecting an appropriate map projection in a Decision Support System (DSS)

USGS Publications Warehouse

Finn, Michael P.; Usery, E. Lynn; Woodard, Laura N.; Yamamoto, Kristina H.

2017-01-01

There are undeniable practical consequences to consider when choosing an appropriate map projection for a specific region. The surface of a globe covered by global, continental, and regional maps are so singular that each type distinctively affects the amount of distortion incurred during a projection transformation because of the an assortment of effects caused by distance, direction, scale , and area. A Decision Support System (DSS) for Map Projections of Small Scale Data was previously developed to help select an appropriate projection. This paper reports on a tutorial to accompany that DSS. The DSS poses questions interactively, allowing the user to decide on the parameters, which in turn determines the logic path to a solution. The objective of including a tutorial to accompany the DSS is achieved by visually representing the path of logic that is taken to a recommended map projection derived from the parameters the user selects. The tutorial informs the DSS user about the pedigree of the projection and provides a basic explanation of the specific projection design. This information is provided by informational pop-ups and other aids.

Watermelon consumption improves inflammation and antioxidant capacity in rats fed an atherogenic diet.

PubMed

Hong, Mee Young; Hartig, Nicole; Kaufman, Katy; Hooshmand, Shirin; Figueroa, Arturo; Kern, Mark

2015-03-01

Cardiovascular disease (CVD) is the leading cause of death in the United States. Watermelon, rich in antioxidants and other bioactive components, may be a viable method to improve CVD risk factors through reduced oxidative stress. The purpose of the study was to determine the effects of watermelon powder consumption on lipid profiles, antioxidant capacity, and inflammation in dextran sodium sulfate (DSS)-treated rats fed an atherogenic diet. We hypothesized that watermelon would increase antioxidant capacity and reduce blood lipids and inflammation through modulation of related gene expression. Forty male-weanling (21 days old) Sprague-Dawley rats were divided into 4 groups (10 per group, total N = 40) in a 2 diets (control or 0.33% watermelon) × 2 treatments (with or without DSS) factorial design using an atherogenic diet. Watermelon-fed groups exhibited significantly lower serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol (P< .05). C-reactive protein levels were significantly lower in watermelon-fed rats than the control (P= .001). In addition, oxidative stress as measured by thiobarbituric acid reactive substances was significantly lower in watermelon groups (P= .001). Total antioxidant capacity, superoxide dismutase, and catalase activities were greater in watermelon groups (P< .05). Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase were significantly lower in DSS-treated rats when watermelon was consumed (P< .05). Fatty acid synthase, 3-hydroxy-3methyl-glutaryl-CoA reductase, sterol regulatory element-binding protein 1, sterol regulatory element-binding protein 2, and cyclooxygenase-2 gene expression was significantly downregulated in the watermelon group without DSS (P< .05). These findings indicate that watermelon improves risk factors for CVD in rats through better lipid profiles, lower inflammation, and greater antioxidant capacity by altering gene expression for lipid

DSS 13 frequency stability tests performed during May 1985 through March 1986

NASA Technical Reports Server (NTRS)

Otoshi, T. Y.; Franco, M. M.

1986-01-01

Results of station frequency stability testing performed at DSS 13 (Deep Space Station) during May 1985 through March 1986 are presented. The testing was done on X-band uplink and X- and S-band downlink subsystems as well as on end-to-end systems. The subsystem test data are useful for assessing the frequency stability of various prototype X-band uplink or downlink subsystems for purposes of making design improvements. Information derived from extensive testing at DSS 13 will be useful in the preparation of an X-band Uplink Demonstration Experiment to be conducted at DSS 13, and will also be valuable in the preparations of gravity wave experiments to be conducted at other DSN stations in the future.

Changes of the peptide YY levels in the intestinal tissue of rats with experimental colitis following oral administration of mesalazine and prednisolone.

PubMed

Hirotani, Yoshihiko; Mikajiri, Kyoko; Ikeda, Kenji; Myotoku, Michiaki; Kurokawa, Nobuo

2008-09-01

Few studies have reported the changes in the peptide YY (PYY) levels in the intestinal tissue of rats with ulcerative colitis (UC) following oral administration of mesalazine and prednisolone. We investigated the effects of these drugs on the intestinal mucosal PYY levels in a rat model of UC. We confirmed that the PYY levels in the rat intestinal mucosal tissue were high in the lower intestinal tract. The leukocyte count and hemoglobin levels approached the normal values after administering mesalazine or prednisolone to rats treated with 3% dextran sulfate sodium (DSS). The PYY levels in the caecum and colon decreased significantly after administering DSS but increased when mesalazine was administered in a tissue-specific manner. Unlike mesalazine, the PYY levels increased in the ileum in addition to the colon and rectum after administering prednisolone. However, neither of the drugs induced any changes in the plasma PYY levels. These findings indicate that changes in the intestinal tissue PYY levels may be partially involved in the improvement of DSS-induced UC in rats following the administration of these drugs.

Salt-Sensitive Hypertension and Cardiac Hypertrophy in Transgenic Mice Expressing a Corin Variant Identified in African Americans

PubMed Central

Wang, Wei; Cui, Yujie; Shen, Jianzhong; Jiang, Jingjing; Chen, Shenghan; Peng, Jianhao; Wu, Qingyu

2012-01-01

African Americans represent a high risk population for salt-sensitive hypertension and heart disease but the underlying mechanism remains unclear. Corin is a cardiac protease that regulates blood pressure by activating natriuretic peptides. A corin gene variant (T555I/Q568P) was identified in African Americans with hypertension and cardiac hypertrophy. In this study, we test the hypothesis that the corin variant contributes to the hypertensive and cardiac hypertrophic phenotype in vivo. Transgenic mice were generated to express wild-type or T555I/Q568P variant corin in the heart under the control of α-myosin heavy chain promoter. The mice were crossed into a corin knockout background to create KO/TgWT and KO/TgV mice that expressed WT or variant corin, respectively, in the heart. Functional studies showed that KO/TgV mice had significantly higher levels of pro-atrial natriuretic peptide in the heart compared with that in control KO/TgWT mice, indicating that the corin variant was defective in processing natriuretic peptides in vivo. By radiotelemetry, corin KO/TgV mice were found to have hypertension that was sensitive to dietary salt loading. The mice also developed cardiac hypertrophy at 12–14 months of age when fed a normal salt diet or at a younger age when fed a high salt diet. The phenotype of salt-sensitive hypertension and cardiac hypertrophy in KO/TgV mice closely resembles the pathological findings in African Americans who carry the corin variant. The results indicate that corin defects may represent an important mechanism in salt-sensitive hypertension and cardiac hypertrophy in African Americans. PMID:22987923

SETI low-frequency feed design study for DSS 24

NASA Technical Reports Server (NTRS)

Stanton, P. H.; Lee, P. R.

1992-01-01

The Search for Extraterrestrial Intelligence Sky Survey project requires operation from 1 to 10 GHz on the beam waveguide (BWG) antenna DSS 24. The BWG reflectors are undersized in the 1- to 3.02-GHz range, resulting in poor performance. Horn designs and a method for implementing 1- to 3.02-GHz operation on DSS 24 are presented. A combination of a horn and a shaped feed reflector placed above the main reflector is suggested. The horn and feed reflector could be hidden in the RF shadow of the subreflector and struts. Results from computer analysis of this design indicate that adequate performance could be achieved.

Cocaine sensitization models an anhedonia-like condition in rats.

PubMed

Scheggi, Simona; Marchese, Giovanna; Grappi, Silvia; Secci, Maria Elena; De Montis, Maria Graziella; Gambarana, Carla

2011-04-01

Anhedonia is a core symptom of depression that also characterizes substance abuse-related mood disorders, in particular those secondary to stimulant abuse. This study investigated the long-lasting condition of cocaine sensitization as an inducing condition for anhedonia in rats. Cortical-mesolimbic dopamine plays a central role in assessing the incentive value of a stimulus and an increased dopamine output in these areas after a novel palatable meal seems to correlate with the ability to acquire an instrumental behaviour aimed at earning it again. This dopaminergic response is associated with consistent modifications in the phosphorylation pattern of some cAMP-dependent protein kinase (PKA) substrates and it is mediated by dopamine D1 receptor stimulation. Thus, since behavioural cocaine sensitization is characterized by tonically increased levels of phospho-Thr75 DARPP-32 that is a potent PKA inhibitor, we hypothesized that cocaine-sensitized rats might reveal deficits in palatable food responding. Indeed, non-food-deprived cocaine-sensitized rats showed no interest in palatable food, no dopaminergic response after a palatable meal in terms of increased dopamine output and DARPP-32 phosphorylation changes, and no ability to acquire a palatable food-sustained instrumental behaviour. Repeated administration of an established antidepressant compound, imipramine, corrected these deficits and reinstated the dopaminergic response in the cortico-mesolimbic areas to control values. Thus, the behavioural modifications observed in cocaine-sensitized rats satisfy some requirements for an experimental model of anhedonia since they are induced by repeated cocaine administration (aetiological validity), they mimic an anhedonia-like symptom (construct validity), and are reversed by the administration of imipramine (predictive validity).

Overexpression of a novel salt stress-induced glycine-rich protein gene from alfalfa causes salt and ABA sensitivity in Arabidopsis.

PubMed

Long, Ruicai; Yang, Qingchuan; Kang, Junmei; Zhang, Tiejun; Wang, Huimin; Li, Mingna; Zhang, Ze

2013-08-01

We cloned a novel salt stress-induced glycine-rich protein gene ( MsGRP ) from alfalfa. Its overexpression retards seed germination and seedling growth of transgenic Arabidopsis after salt and ABA treatments. Since soil salinity is one of the most significant abiotic stresses, salt tolerance is required to overcome salinity-induced reductions in crop productivity. Many glycine-rich proteins (GRPs) have been implicated in plant responses to environmental stresses, but the function and importance of some GRPs in stress responses remain largely unknown. Here, we report on a novel salt stress-induced GRP gene (MsGRP) that we isolated from alfalfa. Compared with some glycine-rich RNA-binding proteins, MsGRP contains no RNA recognition motifs and localizes in the cell membrane or cell wall according to the subcellular localization result. MsGRP mRNA is induced by salt, abscisic acid (ABA), and drought stresses in alfalfa seedlings, and its overexpression driven by a constitutive cauliflower mosaic virus-35S promoter in Arabidopsis plants confers salinity and ABA sensitivity compared with WT plants. MsGRP retards seed germination and seedling growth of transgenic Arabidopsis plants after salt and ABA treatments, which implies that MsGRP may affect germination and growth through an ABA-dependent regulation pathway. These results provide indirect evidence that MsGRP plays important roles in seed germination and seedling growth of alfalfa under some abiotic stress conditions.

Dose-response studies of intracerebroventricular infusion of aldosterone in sensitized and non-sensitized rats.

PubMed

Gomez Sanchez, E P

1988-06-01

We have shown previously that the intracerebroventricular (icvt) infusion of 5 ng/h aldosterone (ALD) in the sensitized rat (one kidney removed, 1% NaCl plus 0.15% KCl solution to drink) produced hypertension similar in amplitude and time of onset to a 100-fold dose administered subcutaneously (s.c.), while a 5-ng/h subcutaneous infusion had no effect on blood pressure (BP). Dose-response studies on the icvt infusion of ALD were carried out in sensitized and non-sensitized (intact, with tap water to drink) male Sprague-Dawley rats (SDR). In both studies, a control group received the diluent, artificial cerebrospinal fluid (CSF), icvt. In sensitized rats, the pressures became significantly (P less than 0.05) elevated at day 7 in those receiving 15 ng/h icvt, day 11 in those receiving 5 ng/h icvt and 500 ng/h s.c. and day 18 in those receiving 1.5 ng/h icvt. The indirect systolic BPs at day 20 of infusion were 119 +/- 0.8 (s.e.) mmHg for controls, 182 +/- 5 for 15 ng/h icvt, 140 +/- 2 mmHg for 5 ng/h icvt, 131 +/- 1 mmHg for 1.5 ng/h icvt, 125 +/- 1 mmHg for 0.5 ng/h, and 159 +/- 5 mmHg for 500 ng/h s.c. Recovery (removal of pumps and return to water to drink) for 18 days resulted in the return of normal pressures in all groups except the 15 ng/h, icvt group in which pressures remained slightly, but significantly elevated at 127 +/- 3 mmHg. In non-sensitized rats, the pressures became significantly elevated in animals receiving 45 ng/h icvt and 1 microgram/h s.c. by day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Status Report on Scoping Reactor Physics and Sensitivity/Uncertainty Analysis of LR-0 Reactor Molten Salt Experiments

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

Brown, Nicholas R.; Mueller, Donald E.; Patton, Bruce W.

2016-08-31

Experiments are being planned at Research Centre Rež (RC Rež) to use the FLiBe (2 7LiF-BeF 2) salt from the Molten Salt Reactor Experiment (MSRE) to perform reactor physics measurements in the LR-0 low power nuclear reactor. These experiments are intended to inform on neutron spectral effects and nuclear data uncertainties for advanced reactor systems utilizing FLiBe salt in a thermal neutron energy spectrum. Oak Ridge National Laboratory (ORNL) is performing sensitivity/uncertainty (S/U) analysis of these planned experiments as part of the ongoing collaboration between the United States and the Czech Republic on civilian nuclear energy research and development. Themore » objective of these analyses is to produce the sensitivity of neutron multiplication to cross section data on an energy-dependent basis for specific nuclides. This report provides a status update on the S/U analyses of critical experiments at the LR-0 Reactor relevant to fluoride salt-cooled high temperature reactor (FHR) and liquid-fueled molten salt reactor (MSR) concepts. The S/U analyses will be used to inform design of FLiBe-based experiments using the salt from MSRE.« less

DNA methylation changes detected by methylation-sensitive amplified polymorphism in two contrasting rice genotypes under salt stress.

PubMed

Wang, Wensheng; Zhao, Xiuqin; Pan, Yajiao; Zhu, Linghua; Fu, Binying; Li, Zhikang

2011-09-20

DNA methylation, one of the most important epigenetic phenomena, plays a vital role in tuning gene expression during plant development as well as in response to environmental stimuli. In the present study, a methylation-sensitive amplified polymorphism (MSAP) analysis was performed to profile DNA methylation changes in two contrasting rice genotypes under salt stress. Consistent with visibly different phenotypes in response to salt stress, epigenetic markers classified as stable inter-cultivar DNA methylation differences were determined between salt-tolerant FL478 and salt-sensitive IR29. In addition, most tissue-specific DNA methylation loci were conserved, while many of the growth stage-dependent DNA methylation loci were dynamic between the two genotypes. Strikingly, salt stress induced a decrease in DNA methylation specifically in roots at the seedling stage that was more profound in IR29 than in the FL478. This result may indicate that demethylation of genes is an active epigenetic response to salt stress in roots at the seedling stage, and helps to further elucidate the implications of DNA methylation in crop growth and development. Copyright © 2011. Published by Elsevier Ltd.

DSS 13 Microprocessor Antenna Controller

NASA Technical Reports Server (NTRS)

Gosline, R. M.

1984-01-01

A microprocessor based antenna controller system developed as part of the unattended station project for DSS 13 is described. Both the hardware and software top level designs are presented and the major problems encounted are discussed. Developments useful to related projects include a JPL standard 15 line interface using a single board computer, a general purpose parser, a fast floating point to ASCII conversion technique, and experience gained in using off board floating point processors with the 8080 CPU.

Sensitive and simultaneous determination of HIV protease inhibitors in rat biological samples by liquid chromatography-mass spectrometry.

PubMed

Gao, Weihua; Kishida, Tomoyuki; Kimura, Keisuke; Kageyama, Michiharu; Sumi, Masaki; Yoshikawa, Yukako; Shibata, Nobuhito; Takada, Kanji

2002-06-01

A sensitive and simultaneous liquid chromatographic-mass spectrometric (LC/MS) method for the determination of current four HIV protease inhibitors (PIs), indinavir (IDV), saquinavir (SQV), nelfinavir (NFV) and amprenavir (APV) in rat plasma and liver dialysate by a microdialysis method was described. An isocratic LC/MS method in combination with atmospheric pressure chemical ionization was developed for the determination of these four PIs in biological samples in the same run. The analytes including an internal standard were extracted from 100 microL of plasma or 150 microL of liver dialysate samples by salting-out with 100 microL of ice-cold 2 M K(3)PO(4) followed by ether extraction. The separation of analytes was carried out on a reversed-phase semi-micro column using 50% of acetonitrile containing 1% acetic acid as mobile phase at a flow rate of 0.2mL/min(-1). The separation was completed within 5 min. Precision, recovery and limits of detection indicated that the method was suitable for the quantitative determination of these PIs in rat plasma or liver dialysate. This simple, sensitive and highly specific LC/MS method is suitable for pharmacokinetic studies and therapeutic drug monitoring in AIDS patients who receive double protease therapy. Copyright 2002 John Wiley & Sons, Ltd.

Reduced NO production rapidly aggravates renal function through the NF-κB/ET-1/ETA receptor pathway in DOCA-salt-induced hypertensive rats.

PubMed

Kimura, Kimihiro; Ohkita, Mamoru; Koyama, Maki; Matsumura, Yasuo

2012-10-15

It has been reported that endothelin-1 (ET-1) overproduction and reduced nitric oxide (NO) production are closely related to the progression of renal diseases. In the present study, we examined the interrelation between ET-1 and NO system using rats treated with the combination of deoxycorticosterone acetate (DOCA)-salt and a non selective NO synthase inhibitor N(ω)-nitro-L-arginine (NOARG). Rats were treated with DOCA-salt (15 mg/kg, plus drinking water containing 1% NaCl) for two weeks, and then additional treatment of NOARG (0.6 mg/ml in the drinking water) was performed for three days. Combined treatment of DOCA-salt and NOARG drastically developed the severe renal dysfunction and tissue injury. This treatment additionally enhanced renal ET-1 production compared to the rats treated with DOCA-salt alone, whereas a selective ET(A) receptor antagonist ABT-627 completely prevented renal dysfunction and tissue injury. On the other hand, combined treatment of DOCA-salt and NOARG induced the phosphorylation of inhibitory protein kappa B (IκB), followed by the activation of nuclear factor-kappa B (NF-κB) in the kidney. In addition, pyrrolidine-dithiocarbamate completely suppressed not only NF-κB activation but also renal dysfunction and ET-1 overproduction. These results suggest that NF-κB/ET-1/ET(A) receptor-mediated actions are responsible for the increased susceptibility to DOCA-salt induced renal injuries in the case of reduced NO production. Copyright © 2012 Elsevier Inc. All rights reserved.

Impact of salt exposure on N-acetylgalactosamine-4-sulfatase (arylsulfatase B) activity, glycosaminoglycans, kininogen, and bradykinin

PubMed Central

Kotlo, Kumar; Bhattacharyya, Sumit; Yang, Bo; Feferman, Leonid; Tejaskumar, Shah; Linhardt, Robert; Danziger, Robert

2013-01-01

N -acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) is the enzyme that removes sulfate groups from the N-acetylgalactosamine-4-sulfate residue at the non-reducing end of chondroitin-4-sulfate (C4S) and dermatan sulfate (DS). Previous studies demonstrated reduction in cell-bound high molecular weight kininogen in normal rat kidney (NRK) epithelial cells when chondroitin-4-sulfate content was reduced following overexpression of ARSB activity, and chondroitinase ABC produced similar decline in cell-bound kininogen. Reduction in the cell-bound kininogen was associated with increase in secreted bradykinin. In this report, we extend the in vitro findings to in vivo models, and present findings in Dahl salt-sensitive (SS) rats exposed to high (SSH) and low salt (SSL) diets. In the renal tissue of the SSH rats, ARSB activity was significantly less than in the SSL rats, and chondroitin-4-sulfate and total sulfated glycosaminoglycan content were significantly greater. Disaccharide analysis confirmed marked increase in C4S disaccharides in the renal tissue of the SSH rats. In contrast, unsulfated, hyaluronan-derived disaccharides were increased in the rats on the low salt diet. In the SSH rats, with lower ARSB activity and higher C4S levels, cell-bound, high-molecular weight kininogen was greater and urinary bradykinin was lower. ARSB activity in renal tissue and NRK cells declined when exogenous chloride concentration was increased in vitro. The impact of high chloride exposure in vivo on ARSB, chondroitin-4-sulfation, and C4S-kininogen binding provides a mechanism that links dietary salt intake with bradykinin secretion and may be a factor in blood pressure regulation. PMID:23385884

Impact of salt exposure on N-acetylgalactosamine-4-sulfatase (arylsulfatase B) activity, glycosaminoglycans, kininogen, and bradykinin.

PubMed

Kotlo, Kumar; Bhattacharyya, Sumit; Yang, Bo; Feferman, Leonid; Tejaskumar, Shah; Linhardt, Robert; Danziger, Robert; Tobacman, Joanne K

2013-10-01

N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) is the enzyme that removes sulfate groups from the N-acetylgalactosamine-4-sulfate residue at the non-reducing end of chondroitin-4-sulfate (C4S) and dermatan sulfate (DS). Previous studies demonstrated reduction in cell-bound high molecular weight kininogen in normal rat kidney (NRK) epithelial cells when chondroitin-4-sulfate content was reduced following overexpression of ARSB activity, and chondroitinase ABC produced similar decline in cell-bound kininogen. Reduction in the cell-bound kininogen was associated with increase in secreted bradykinin. In this report, we extend the in vitro findings to in vivo models, and present findings in Dahl salt-sensitive (SS) rats exposed to high (SSH) and low salt (SSL) diets. In the renal tissue of the SSH rats, ARSB activity was significantly less than in the SSL rats, and chondroitin-4-sulfate and total sulfated glycosaminoglycan content were significantly greater. Disaccharide analysis confirmed marked increase in C4S disaccharides in the renal tissue of the SSH rats. In contrast, unsulfated, hyaluronan-derived disaccharides were increased in the rats on the low salt diet. In the SSH rats, with lower ARSB activity and higher C4S levels, cell-bound, high-molecular weight kininogen was greater and urinary bradykinin was lower. ARSB activity in renal tissue and NRK cells declined when exogenous chloride concentration was increased in vitro. The impact of high chloride exposure in vivo on ARSB, chondroitin-4-sulfation, and C4S-kininogen binding provides a mechanism that links dietary salt intake with bradykinin secretion and may be a factor in blood pressure regulation.

Psychological Stress Induces Temporary Masticatory Muscle Mechanical Sensitivity in Rats

PubMed Central

Huang, Fei; Zhang, Min; Chen, Yong-Jin; Li, Qiang; Wu, An-Zhen

2011-01-01

To explore the relationship between psychological stress and masticatory muscle pain, we created a communication stress animal model to determine whether psychological stress could induce increased mechanical sensitivity in masticatory muscles and to study the changes of mechanical nociceptive thresholds after stress removal. Forty-eight male Sprague-Dawley rats were divided into a control group (CON), a foot-shocked group (FS, including 3 subgroups recorded as FS-1, FS-2, and FS-3), a psychological stress group (PS), and a drug treatment group (DT). PS and DT rats were confined in a communication box for one hour a day to observe the psychological responses of neighboring FS rats.Measurements of the mechanical nociceptive thresholds of the bilateral temporal and masseter muscles showed a stimulus-response relationship between psychological stress and muscle mechanical sensitivity. The DT rats, who received a diazepam injection, showed almost the same mechanical sensitivity of the masticatory muscles to that of the control in response to psychological stress. Fourteen days after the psychological stressor was removed, the mechanical nociceptive thresholds returned to normal. These findings suggest that psychological stress is directly related to masticatory muscle pain. Removal of the stressor could be a useful method for relieving mechanical sensitivity increase induced by psychological stress. PMID:21331360

Vectorial transport of unconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected with human NTCP and BSEP or with rat Ntcp and Bsep.

PubMed

Mita, Sachiko; Suzuki, Hiroshi; Akita, Hidetaka; Hayashi, Hisamitsu; Onuki, Reiko; Hofmann, Alan F; Sugiyama, Yuichi

2006-03-01

Na(+)-taurocholate-cotransporting peptide (NTCP)/SLC10A1 and bile salt export pump (BSEP)/ABCB11 synergistically play an important role in the transport of bile salts by the hepatocyte. In this study, we transfected human NTCP and BSEP or rat Ntcp and Bsep into LLC-PK1 cells, a cell line devoid of bile salts transporters. Transport by these cells was characterized with a focus on substrate specificity between rats and humans. The basal to apical flux of taurocholate across NTCP- and BSEP-expressing LLC-PK1 monolayers was 10 times higher than that in the opposite direction, whereas the flux across the monolayer of control and NTCP or BSEP single-expressing cells did not show any vectorial transport. The basal to apical flux of taurocholate was saturated with a K(m) value of 20 microM. Vectorial transcellular transport was also observed for cholate, chenodeoxycholate, ursodeoxycholate, their taurine and glycine conjugates, and taurodeoxycholate and glycodeoxycholate, whereas no transport of lithocholate was detected. To evaluate the respective functions of NTCP and BSEP and to compare them with those of rat Ntcp and Bsep, we calculated the clearance by each transporter in this system. A good correlation in the clearance of the examined bile salts (cholate, chenodeoxycholate, ursodeoxycholate, and their taurine or glycine conjugates) was observed between transport by human and that of rat transporters in terms of their rank order: for NTCP, taurine conjugates > glycine conjugates > unconjugated bile salts, and for BSEP, unconjugated bile salts and glycine conjugates > taurine conjugates. In conclusion, the substrate specificity of human and rat NTCP and BSEP appear to be very similar at least for monovalent bile salts under physiological conditions.

The spatial learning and memory performance in methamphetamine–sensitized and withdrawn rats

PubMed Central

Bigdeli, Imanollah; Asia, Masomeh Nikfarjam- Haft; Miladi-Gorji, Hossein; Fadaei, Atefeh

2015-01-01

Objective(s): There is controversial evidence about the effect of methamphetamine (METH) on spatial memory. We tested the time- dependent effects of METH on spatial short-term (working) and long-term (reference) memory in METH –sensitized and withdrawn rats in the Morris water maze. Materials and Methods: Rats were sensitized to METH (2 mg/kg, daily/5 days, SC). Rats were trained in water maze (4 trials/day/for 5 days). Probe test was performed 24 hr after training. Two days after probe test, working memory training (2 trials/day/for 5 days) was conducted. Acquisition–retention interval was 75 min. The treatment was continued per day 30 and 120 min before the test. Two groups of METH –sensitized rats were trained in reference memory after a longer period of withdrawal (30 days). Results: Sensitized rats exhibited significantly longer escape latencies on the training, spent significantly less time in the target zone (all, P<0.05), and their working memory impaired 30 min after injection. While, METH has no effect on the spatial learning process 120 min after injection, and rats spent significantly less time in the target zone (P<0.05), as well it has no effect on working memory. Also, impairment of reference memory persisted after prolonged abstinence. Conclusion: Our findings indicated that METH impaired spatial learning and memory 30 min after injection, but spared spatial learning, either acquisition or retention of spatial working, but partially impaired retention of spatial reference memory following 120 min after injection in sensitized rats, which persisted even after prolonged abstinence. PMID:25945235

Enhancement of brain-targeting delivery of danshensu in rat through conjugation with pyrazine moiety to form danshensu-pyrazine ester.

PubMed

Hui, Ailing; Yin, Huayang; Zhang, Zheng; Zhou, An; Chen, Jingchao; Yang, Li; Wu, Zeyu; Zhang, Wencheng

2018-06-01

Tetramethylpyrazine was introduced to the structure of danshensu (DSS) as P-glycoprotein (P-gp)-inhibiting carrier, designing some novel brain-targeting DSS-pyrazine derivatives via prodrug delivery strategy. Following the virtual screening, three DSS-pyrazine esters (DT1, DT2, DT3) were selected because of their better prediction parameters related to brain-targeting. Among them, DT3 was thought to be a promising candidate due to its appropriate bioreversible property in vitro release assay. Further investigation with regard to DT3's brain-targeting effects in vivo was also reported in this study. High-performance liquid chromatography-diode array detection (HPLC-DAD) method was established for the quantitative determination of DT3 and DSS in rat plasma, brain homogenate after intravenous injection. In vivo metabolism of DT3 indicated that it was first converted into DT1, DT2, then the generation of DSS, which could be the result of carboxylesterase activity in rat blood and brain tissue. Moreover, the brain pharmacokinetics of DT3 was significantly altered with 2.16 times increase in half-life compared with that of DSS, and its drug targeting index (DTI) was up to 16.95. Above these data demonstrated that DT3 had better tendency of brain-targeting delivery, which would be positive for the treatment of brain-related disorders.

Changes in hydraulic conductance cause the difference in growth response to short-term salt stress between salt-tolerant and -sensitive black gram (Vigna mungo) varieties.

PubMed

Win, Khin Thuzar; Oo, Aung Zaw; Ookawa, Taiichiro; Kanekatsu, Motoki; Hirasawa, Tadashii

2016-04-01

Black gram (Vigna mungo) is an important crop in Asia, However, most black gram varieties are salt-sensitive. The causes of varietal differences in salt-induced growth reduction between two black gram varieties, 'U-Taung-2' (salt-tolerant; BT) and 'Mut Pe Khaing To' (salt-sensitive; BS), were examined the potential for the first step toward the genetic improvement of salt tolerance. Seedlings grown in vermiculite irrigated with full-strength Hoagland solution were treated with 0mM NaCl (control) or 225 mM NaCl for up to 10 days. In the 225 mM NaCl treatment, plant growth rate, net assimilation rate, mean leaf area, leaf water potential, and leaf photosynthesis were reduced more in BS than in BT plants. Leaf water potential was closely related to leaf photosynthesis, net assimilation rate, and increase in leaf area. In response to salinity stress, hydraulic conductance of the root, stem, and petiole decreased more strongly in BS than in BT plants. The reduction in stem and petiole hydraulic conductance was caused by cavitation, whereas the reduction in root hydraulic conductance in BS plants was caused by a reduction in root surface area and hydraulic conductivity. We conclude that the different reduction in hydraulic conductance is a cause of the differences in the growth response between the two black gram varieties under short-term salt stress. Copyright © 2016 Elsevier GmbH. All rights reserved.

Blood Pressure Genetic Risk Score Predicts Blood Pressure Responses to Dietary Sodium and Potassium: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity).

PubMed

Nierenberg, Jovia L; Li, Changwei; He, Jiang; Gu, Dongfeng; Chen, Jichun; Lu, Xiangfeng; Li, Jianxin; Wu, Xigui; Gu, C Charles; Hixson, James E; Rao, Dabeeru C; Kelly, Tanika N

2017-12-01

We examined the association between genetic risk score (GRS) for blood pressure (BP), based on single nucleotide polymorphisms identified in previous BP genome-wide association study meta-analyses, and salt and potassium sensitivity of BP among participants of the GenSalt study (Genetic Epidemiology Network of Salt Sensitivity). The GenSalt study was conducted among 1906 participants who underwent a 7-day low-sodium (51.3 mmol sodium/d), 7-day high-sodium (307.8 mmol sodium/d), and 7-day high-sodium plus potassium (60 mmol potassium/d) intervention. BP was measured 9× at baseline and at the end of each intervention period using a random zero sphygmomanometer. Associations between systolic BP (SBP), diastolic BP, and mean arterial pressure GRS and respective SBP, diastolic BP, and mean arterial pressure responses to the dietary interventions were assessed using mixed linear regression models that accounted for familial dependencies and adjusted for age, sex, field center, body mass index, and baseline BP. As expected, baseline SBP, diastolic BP, and mean arterial pressure significantly increased per quartile increase in GRS ( P =2.7×10 -8 , 9.8×10 -8 , and 6.4×10 -6 , respectively). In contrast, increasing GRS quartile conferred smaller SBP, diastolic BP, and mean arterial pressure responses to the low-sodium intervention ( P =1.4×10 -3 , 0.02, and 0.06, respectively) and smaller SBP responses to the high-sodium and potassium interventions ( P =0.10 and 0.05). In addition, overall findings were similar when examining GRS as a continuous measure. Contrary to our initial hypothesis, we identified an inverse relationship between BP GRS and salt and potassium sensitivity of BP. These data may provide novel implications on the relationship between BP responses to dietary sodium and potassium and hypertension. © 2017 American Heart Association, Inc.

Impact assessment and recommendation of alternative conjunctive water use strategies for salt affected agricultural lands through a field scale decision support system - a case study.

PubMed

Kaur, Ravinder; Paul, Madhumita; Malik, Rashmi

2007-06-01

Conjunctive use of saline/non-saline irrigation waters is generally aimed at minimizing yield losses and enhancing flexibility of cropping, without much alteration in farming operations. Recommendation of location-specific suitable conjunctive water use plans requires assessment of their long-term impacts on soil salinization/sodification and crop yield reductions. This is conventionally achieved through long-term field experiments. However such impact evaluations are site specific, expensive and time consuming. Appropriate decision support systems (DSS) can be time-efficient and cost-effective means for such long-term impact evaluations. This study demonstrates the application of one such (indigenously developed) DSS for recommending best conjunctive water use plans for a, rice-wheat growing, salt affected farmer's field in Gurgaon district of Haryana (India). Before application, the DSS was extensively validated on several farmers and controlled experimental fields in Gurgaon and Karnal districts of Haryana (India). Validation of DSS showed its potential to give realistic estimates of root zone soil salinity (with R = 0.76-0.94; AMRE = 0.03-0.06; RMSPD = 0.51-0.90); sodicity (with R = 0.99; AMRE = 0.02; RMSPD = 0.84) and relative crop yield reductions (AMRE = 0.24), under existing (local) resource management practices. Long term (10 years) root zone salt build ups and associated rice/wheat crop yield reductions, in a salt affected farmer's field, under varied conjunctive water use scenarios were evaluated with the validated DSS. It was observed that long-term applications of canal (CW) and tube well (TW) waters in a cycle and in 1:1 mixed mode, during Kharif season, predicted higher average root zone salt reductions (2-9%) and lower rice crop yield reductions (4-5%) than the existing practice of 3-CW, 3-TW, 3-CW. Besides this, long-term application of 75% CW mixed with 25% TW, during Rabi season, predicted about 17% lower average root-zone salt reductions than

Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats.

PubMed

Hodges, Matthew R; Echert, Ashley E; Puissant, Madeleine M; Mouradian, Gary C

2013-04-01

The Brown Norway (BN; BN/NHsdMcwi) rat exhibits a deficit in ventilatory CO2 sensitivity and a modest serotonin (5-HT) deficiency. Here, we tested the hypothesis that the selective serotonin reuptake inhibitor fluoxetine would augment CO2 sensitivity in BN but not Sprague Dawley (SD) rats. Ventilation during room air or 7% CO2 exposure was measured before, during and after 3 weeks of daily injections of saline or fluoxetine (10mg/(kgday)) in adult male BN and SD rats. Fluoxetine had minimal effects on room air breathing in BN and SD rats (p>0.05), although tidal volume (VT) was reduced in BN rats (p<0.05). There were also minimal effects of fluoxetine on CO2 sensitivity in SD rats, but fluoxetine increased minute ventilation, breathing frequency and VT during hypercapnia in BN rats (p<0.05). The augmented CO2 response was reversible upon withdrawal of fluoxetine. Brain levels of biogenic amines were largely unaffected, but 5-HIAA and the ratio of 5-HIAA/5-HT were reduced (p<0.05) consistent with selective and effective 5-HT reuptake inhibition. Thus, fluoxetine increases ventilatory CO2 sensitivity in BN but not SD rats, further suggesting altered 5-HT system function may contribute to the inherently low CO2 sensitivity in the BN rat. Copyright © 2013 Elsevier B.V. All rights reserved.

Dextran sulphate sodium (DSS) causes intestinal histopathology and inflammatory changes consistent with increased gut leakiness in chickens.

PubMed

Zou, X; Ji, J; Wang, J; Qu, H; Shu, D M; Guo, F Y; Luo, C L

2018-04-01

1. The clinical severity, histological changes, indicators of gut leakiness and inflammatory cytokine profiles were studied in chickens with dextran sulphate sodium (DSS)-induced intestinal inflammation. 2. The experimental groups (1.25%, 1.5% and 2.5% DSS) showed clinical signs, such as loose stools and weight loss, which increased with additional treatment days and, as expected, the effects of DSS-induced intestinal inflammation were time and dose-dependent. 3. After 10 d, histological manifestations were evident, including goblet cell depletion, mucus layer loss, significantly shorter villi and a thinner total ileal mucosa. 4. The d(-)-lactate value, which was used as a gut leakiness indicator, was significantly increased in the 2.5% DSS group. 5. Expression of the inflammatory cytokines interleukin-1Beta, tumour necrosis factor alpha and interleukin-10 in the serum significantly increased with DSS treatment. 6. This study indicates that the experimental intestinal inflammation induced by DSS is an ideal model to study the pathogenic mechanisms of intestinal inflammation in chickens and to test the efficacy of therapies.

Sensitivity to apomorphine-induced yawning and hypothermia in rats eating standard or high-fat chow.

PubMed

Baladi, Michelle G; Thomas, Yvonne M; France, Charles P

2012-07-01

Feeding conditions modify sensitivity to indirect- and direct-acting dopamine receptor agonists as well as the development of sensitization to these drugs. This study examined whether feeding condition affects acute sensitivity to apomorphine-induced yawning or changes in sensitivity that occur over repeated drug administration. Quinpirole-induced yawning was also evaluated to see whether sensitization to apomorphine confers cross-sensitization to quinpirole. Drug-induced yawning was measured in different groups of male Sprague Dawley rats (n = 6/group) eating high (34.3%) fat or standard (5.7% fat) chow. Five weeks of eating high-fat chow rendered otherwise drug-naïve rats more sensitive to apomorphine- (0.01-1.0 mg/kg, i.p.) and quinpirole- (0.0032-0.32 mg/kg, i.p.) induced yawning, compared with rats eating standard chow. In other rats, tested weekly with apomorphine, sensitivity to apomorphine-induced yawning increased (sensitization) similarly in rats with free access to standard or high-fat chow; conditioning to the testing environment appeared to contribute to increased yawning in both groups of rats. Food restriction decreased sensitivity to apomorphine-induced yawning across five weekly tests. Rats with free access to standard or high-fat chow and sensitized to apomorphine were cross-sensitized to quinpirole-induced yawning. The hypothermic effects of apomorphine and quinpirole were not different regardless of drug history or feeding condition. Eating high-fat chow or restricting access to food alters sensitivity to direct-acting dopamine receptor agonists (apomorphine, quinpirole), although the relative contribution of drug history and dietary conditions to sensitivity changes appears to vary among agonists.

High Salt Intake Increases Blood Pressure in Normal Rats: Putative Role of 20-HETE and No Evidence on Changes in Renal Vascular Reactivity

PubMed Central

Walkowska, A.; Kuczeriszka, M.; Sadowski, J.; Olszyński, K.H.; Dobrowolski, L.; Červenka, L.; Hammock, B.D.; Kompanowska-Jezierska, E.

2015-01-01

Background/Aims High salt (HS) intake may elevate blood pressure (BP), also in animals without genetic salt sensitivity. The development of salt-dependent hypertension could be mediated by endogenous vasoactive agents; here we examined the role of vasodilator epoxyeicosatrienoic acids (EETs) and vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE). Methods In conscious Wistar rats on HS diet systolic BP (SBP) was examined after chronic elevation of EETs using 4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (c-AUCB), a blocker of soluble epoxide hydrolase, or after inhibition of 20-HETE with 1-aminobenzotriazole (ABT). Thereafter, in acute experiments the responses of renal artery blood flow (Transonic probe) and renal regional perfusion (laser-Doppler) to intrarenal acetylcholine (ACh) or norepinephrine were determined. Results HS diet increased urinary 20-HETE excretion. The SBP increase was not reduced by c-AUCB but prevented by ABT until day 5 of HS exposure. Renal vasomotor responses to ACh or norepinephrine were similar on standard and HS diet. ABT but not c-AUCB abolished the responses to ACh. Conclusions 20-HETE seems to mediate the early-phase HS diet-induced BP increase while EETs are not engaged in the process. Since HS exposure did not alter renal vasodilator responses to Ach, endothelial dysfunction is not a critical factor in the mechanism of salt-induced blood pressure elevation. PMID:26067851

Lecithin inhibits fatty acid and bile salt absorption from rat small intestine in vivo.

PubMed

Saunders, D R; Sillery, J

1976-12-01

During digestion of a fatty meal, long chain free fatty acids (FFA) and lecithin are among the lipids solubilized in intestinal contents as mixed micelles with bile salts. We hypothesized that if lecithin were not hydrolyzed, the mixed micelles would be abnormal, and absorption of FFA and bile salts would be depressed. To test this hypothesis, isolated segments of rat small intestine were infused in vivo with micellar solutions of 2 mMolar linoleic acid and 10 mMolar taurocholate to which was added 3 mMolar 1-palmitoyl, 2-oleoyl lecithin (a common lecithin in bile and food), or 1-palmitoyl lysolecithin (the hydrolytic product of lecithin). Absorption of FFA and bile salt was measured under steady state conditions using a single-pass technique. Lecithin depressed the rate of FFA absorption by 40% (p less than 0.025) in jejunal and ileal segments whereas lysolecithin was associated with normal rates of FFA absorption. Lecithin also reduced taurocholate absorption from the ileum by 30% (p less than 0.05). These data support the idea that lecithin may depress FFA and bile salt absorption from the small intestine in pancreatic insufficiency.

Improving an Atlantic Fisheries DSS using Sea Surface Salinity Data from NASA's Aquarius Mission

NASA Technical Reports Server (NTRS)

Guest, DeNeice

2007-01-01

This report assesses the capacity of incorporating NASA#s Aquarius SSS (sea surface salinity) data into the SMAST (School of Marine Science and Technology) DSS for Fisheries Science. This data will enhance the SMAST DSS by providing SSS over a large area. Aquarius is a focused satellite mission designed to measure global SSS. SSS mapping is limited because conventional in situ SSS sampling is too sparse to give a large-scale view of the salinity variability. Aquarius will resolve missing physical processes that link the water cycle, the climate, and the ocean. The SMAST Fisheries program provides a DSS for fisheries science. It collects fisheries and environmental data, integrates them into a suite of data assimilation ocean models, and provides hindcasts, nowcasts, and forecasts for fisheries research, fisheries management, and the fishery industry. Currently, SMAST is using SSS data from the National Oceanic and Atmospheric Administration#s National Data Buoy Center. The SMAST DSS would be enhanced with SSS data from the Aquarius mission.

The development of an EDSS: Lessons learned and implications for DSS research

USGS Publications Warehouse

El-Gayar, O.; Deokar, A.; Michels, L.; Fosnight, G.

2011-01-01

The Solar and Wind Energy Resource Assessment (SWERA) project is focused on providing renewable energy (RE) planning resources to the public. Examples include wind, solar, and hydro assessments. SWERA DSS consists of three major components. First, SWERA 'Product Archive' provides for a discovery DSS upon which users can find and access renewable energy data and supporting models. Second, the 'Renewable Resource EXplorer' (RREX) component serves as a web-based, GIS analysis tool for viewing RE resource data available through the SWERA Product Archive. Third, the SWERA web service provides computational access to the data available in the SWERA spatial database through a location based query, and is also utilized in the RREX component. We provide a discussion of various design decisions used in the construction of this EDSS, followed by project experiences and implications for EDSS and broader DSS research. ?? 2011 IEEE.

The effect of varenicline on the development and expression of nicotine-induced behavioral sensitization and cross-sensitization in rats.

PubMed

Goutier, Wouter; Kloeze, Margreet B; McCreary, Andrew C

2015-03-01

The present study focused on the evaluation of behavioral sensitization and cross-sensitization induced by nicotine and varenicline in rats. Furthermore, it examined the influence of varenicline, a partial alpha4beta2 nicotinic receptor agonist, on nicotine-induced sensitization. To assess the development of behavioral sensitization, rats were chronically treated with vehicle, varenicline (0.03-3.0 mg/kg), nicotine (0.4 mg/kg) or combinations for 5 days and locomotor activity was measured. The expression of sensitization was assessed following a withdrawal period (17-26 days). The present results confirmed previous data showing the development and expression of nicotine-induced sensitization of locomotor activity in the rat. Varenicline did not induce sensitization on its own. When varenicline and nicotine were repeatedly administered sequentially, varenicline blocked the development and expression of nicotine-induced sensitization. Acute varenicline blocked the expression of nicotine-induced sensitization in a dose-dependent manner. Acute varenicline did not significantly increase locomotor activity, nor did it attenuate nicotine-induced sensitization. However, varenicline did cross-sensitize to the effects of nicotine, and vice versa. The present study showed that varenicline produced a dose-dependent bidirectional cross-sensitization with nicotine. Taken together, these findings provide pre-clinical evidence that varenicline is able to attenuate the effects of nicotine, yet simultaneously 'substitutes' for the effects of nicotine in the rat. Longitudinal studies would be needed to see if similar effects are seen in the clinical setting, and whether such effects contribute to the actions of varenicline as a smoking cessation aid. © 2013 Society for the Study of Addiction.

Sex determining gene on the X chromosome short arm: dosage sensitive sex reversal.

PubMed

Ogata, T; Matsuo, N

1996-08-01

The present review article summarizes current knowledge concerning the sex determining gene on Xp21, termed DSS (dosage sensitive sex reversal). The presence of DSS has been based on the finding that, in the presence of SRY, partial active Xp duplications encompassing the middle part of Xp result in sex reversal, whereas those of the distal or proximal part of Xp permit male sex development. Because Klinefelter patients develop as males, it is believed that DSS is normally subject to X-inactivation, and that two active copies of DSS override the function of SRY, resulting in gonadal dysgenesis because of meiotic pairing failure. It may be possible that DSS encodes a target sequence for repressing function of SRY or that DSS is involved in an X chromosome-counting mechanism. Molecular approaches have localized DSS to a 160 kb region and isolated candidate genes such as DAX-1 and MAGE-Xp, but there has been no formal evidence equating the candidate gene with DSS. In addition to its clinical importance, the exploration of DSS must provide a useful clue to phylogenetic studies of sex chromosomes and dosage compensation.

Behavioral cross-sensitization between DOCA-induced sodium appetite and cocaine-induced locomotor behavior

PubMed Central

Acerbo, Martin J.; Johnson, Alan Kim

2011-01-01

Behavioral sensitization involves increases in the magnitude of a response to a stimulus after repeated exposures to the same response initiator. Administration of psychomotor stimulants and the induction of appetitive motivational states associated with natural reinforcers like sugar and salt are among experimental manipulations producing behavioral sensitization. In rats, repeated administration of the mineralocorticoid agonist deoxycorticosterone acetate (DOCA) initially induces incremental increases in daily hypertonic saline consumption (i.e., sensitization of sodium appetite) in spite of the retention of sodium. The present studies investigated whether sodium appetite sensitization induced by DOCA shares mechanisms similar to those of psychomotor stimulant-induced sensitization, and whether there is evidence for reciprocal cross-sensitization. In Experiments 1 and 3, rats received control or cocaine treatments to induce locomotor sensitization. A week later DOCA (or vehicle) was administered to generate a sodium appetite. Animals pretreated with cocaine showed a greater sodium appetite. In Experiment 2, the order of the putative sensitizing treatments was reversed. Rats first received either a series of DOCA or vehicle treatments either with or without access to saline and were later tested for sensitization of the locomotor response to cocaine. Animals pretreated with DOCA without access to saline showed greater locomotor responses to cocaine than animals receiving vehicle treatments. Together these experiments indicate that treatments generating a sustained salt appetite and producing cocaine-induced psychomotor responses show reciprocal behavioral cross-sensitization. The underlying mechanisms accounting for this relationship may be the fact that psychostimulants and an unresolved craving for sodium can act as potent stressors. PMID:21352848

Integrated river basin management, ICT and DSS: Challenges and needs

NASA Astrophysics Data System (ADS)

Gourbesville, Philippe

River basin management is a complex task. Therefore, instruments that help to assess the present situation and assist in the development and evaluation of solutions may be important. Since several decades and after the implementation of the first compulsory legal environments and institutional organizations for IWRM and IRBM, the need for an efficient support in the different decision-making processes has emerged. After several experiences, the demonstration of the interest of ICT and DSS systems is obvious in the water resources management domain. However and until now, most of the efforts have been focused on the theoretical aspects with very few integrations into operational approaches. The implementation of the new European water framework directive (2000) represents today one key example from which some lessons can be learned in the way of definition and use of ICT and DSS systems for IWRM and IRBM. The paper presents the concepts available through ICT and DSS. The example of the WFD is used to underline the challenges and the difficulties for the elaboration of new tools - DSSs - which could be able to answer of the challenges of IWRM and IRBM.

Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats

PubMed Central

Senol, Altug; Isler, Mehmet; Sutcu, Recep; Akin, Mete; Cakir, Ebru; Ceyhan, Betul M; Kockar, M Cem

2015-01-01

AIM: To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium (DSS) in rats. METHODS: Twenty-four male Wistar-albino rats were randomized into four groups: normal control, kefir-control, colitis, and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir-colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 mL kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo (skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index (DAI), based on daily weight loss, stool consistency, and presence of bleeding in feces. Rats were sacrificed on the 15th day, blood specimens were collected, and colon tissues were rapidly removed. Levels of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-10, malondialdehyde, and inducible nitric oxide synthase (iNOS) were measured in colon tissue. RESULTS: The DAI was lower in the kefir-colitis group than in the colitis group (on the 3rd and 5th days of colitis induction; P < 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6th day in the kefir-colitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis-induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores (P < 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group (P < 0

Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats.

PubMed

Senol, Altug; Isler, Mehmet; Sutcu, Recep; Akin, Mete; Cakir, Ebru; Ceyhan, Betul M; Kockar, M Cem

2015-12-14

To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium (DSS) in rats. Twenty-four male Wistar-albino rats were randomized into four groups: normal control, kefir-control, colitis, and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir-colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 mL kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo (skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index (DAI), based on daily weight loss, stool consistency, and presence of bleeding in feces. Rats were sacrificed on the 15(th) day, blood specimens were collected, and colon tissues were rapidly removed. Levels of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-10, malondialdehyde, and inducible nitric oxide synthase (iNOS) were measured in colon tissue. The DAI was lower in the kefir-colitis group than in the colitis group (on the 3(rd) and 5(th) days of colitis induction; P < 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6(th) day in the kefir-colitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis-induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores (P < 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group (P < 0.05). Kefir treatment

Multi-criteria Decision Support System (DSS) for optimal locations of Soil Aquifer Treatment (SAT) facilities.

PubMed

Tsangaratos, P; Kallioras, A; Pizpikis, Th; Vasileiou, E; Ilia, I; Pliakas, F

2017-12-15

Managed Aquifer Recharge is a wide-spread well-established groundwater engineering method which is largely seen as sound and sustainable solution to water scarcity hydrologically sensitive areas, such as the Circum Mediterranean. The process of site selection for the installation of a MAR facility is of paramount importance for the feasibility and effectiveness of the project itself, especially when the facility will include the use of waters of impaired quality as a recharge source, as in the case of Soil-Aquifer-Treatment systems. The main objective of this study is to present the developed framework of a multi-criteria Decision Support System (DSS) that integrates within a dynamic platform the main groundwater engineering parameters associated with MAR applications together with the general geographical features which determine the effectiveness of such a project. The proposed system will provide an advanced coupled DSS-GIS tool capable of handling local MAR-related issues -such as hydrogeology, topography, soil, climate etc., and spatially distributed variables -such as societal, economic, administrative, legislative etc., with special reference to Soil-Aquifer-Treatment technologies. Copyright © 2017 Elsevier B.V. All rights reserved.

Rosiglitazone Improves Insulin Sensitivity and Baroreflex Gain in Rats with Diet-Induced Obesity

PubMed Central

Zhao, Ding; McCully, Belinda H.

2012-01-01

Obesity decreases baroreflex gain (BRG); however, the mechanisms are unknown. We tested the hypothesis that impaired BRG is related to the concurrent insulin resistance, and, therefore, BRG would be improved after treatment with the insulin-sensitizing drug rosiglitazone. Male rats fed a high-fat diet diverged into obesity-prone (OP) and obesity-resistant (OR) groups after 2 weeks. Then, OP and OR rats, as well as control (CON) rats fed a standard diet, were treated daily for 2 to 3 weeks with rosiglitazone (3 or 6 mg/kg) or its vehicle by gavage. Compared with OR and CON rats, conscious OP rats exhibited reductions in BRG (OP, 2.9 ± 0.1 bpm/mm Hg; OR, 4.0 ± 0.2 bpm/mm Hg; CON, 3.9 ± 0.2 bpm/mm Hg; P < 0.05) and insulin sensitivity (hyperinsulinemic euglycemic clamp; OP, 6.8 ± 0.9 mg/kg · min; OR, 22.2 ± 1.2 mg/kg · min; CON, 17.7 ± 0.8 mg/kg · min; P < 0.05), which were well correlated (r2 = 0.49; P < 0.01). In OP rats, rosiglitazone dose-dependently improved (P < 0.05) insulin sensitivity (12.8 ± 0.6 mg/kg · min at 3 mg/kg; 16.0 ± 1.5 mg/kg · min at 6 mg/kg) and BRG (3.8 ± 0.4 bpm/mm Hg at 3 mg/kg; 5.3 ± 0.7 bpm/mm Hg at 6 mg/kg). However, 6 mg/kg rosiglitazone also increased BRG in OR rats without increasing insulin sensitivity, disrupted the correlation between BRG and insulin sensitivity (r2 = 0.08), and, in OP and OR rats, elevated BRG relative to insulin sensitivity (analysis of covariance; P < 0.05). Moreover, in OP rats, stimulation of the aortic depressor nerve, to activate central baroreflex pathways, elicited markedly reduced decreases in heart rate and arterial pressure, but these responses were not improved by rosiglitazone. In conclusion, diet-induced obesity impairs BRG via a central mechanism that is related to the concurrent insulin resistance. Rosiglitazone normalizes BRG, but not by improving brain baroreflex processing or insulin sensitivity. PMID:22815534

Intracerebroventricular Injection of Rats. A Sensitive Assay Method for Endogenous Pyrogen Circulating in Rats (41015)

DTIC Science & Technology

1981-01-01

Rats:1A Sensitive Assay Method for Endogenous Pyrogen Circulating in Rats (41015)1-- / WALTER J.CRITZ ~fI~ U.S. Army Medical Resetirch Inshfute- riak...8217ohn iases. F’oPy Detrick, Frederick. Maryland 21701 OI! Abstract, Intracerebroventricular tics) injection of endogenous pyrogen (EPI into rats causes...the lower the con- in an alteration of the "set-point" for body centration at which the pyrogen can be temperature (2). Endogenous pyrogen is a

Potassium Inhibits Dietary Salt-Induced Transforming Growth Factor-β Production

PubMed Central

Ying, Wei-Zhong; Aaron, Kristal; Wang, Pei-Xuan; Sanders, Paul W.

2009-01-01

Human and animal studies demonstrate an untoward effect of excess dietary NaCl (salt) intake on cardiovascular function and life span. The endothelium in particular augments the production of transforming growth factor (TGF)-β, a fibrogenic growth factor, in response to excess dietary salt intake. This study explored the initiating mechanism that regulates salt-induced endothelial cell production of TGF-β. Male Sprague-Dawley rats were given diets containing different amounts of NaCl and potassium for 4 days. A bioassay for TGF-β demonstrated increased (35.2%) amounts of active TGF-β in the medium of aortic ring segments from rats on the high-salt diet compared with rats maintained on a 0.3% NaCl diet. Inhibition of the large-conductance, calcium-activated potassium channel inhibited dietary salt-induced vascular production of TGF-β but did not affect production of TGF-β by ring segments from rats on the low-salt diet. Immunohistochemical and Western analyses demonstrated the α subunit of the calcium-activated potassium channel in endothelial cells. Increasing medium [K+] inhibited production of dietary salt-induced vascular production levels of total and active TGF-β but did not alter TGF-β production by aortic rings from rats on the 0.3% NaCl diet. Increasing dietary potassium content decreased urinary active TGF-β in animals receiving the high-salt diet but did not change urinary active TGF-β in animals receiving the low-salt diet. The findings demonstrated an interesting interaction between the dietary intake of potassium and excess NaCl and further showed the fundamental role of the endothelial calcium-activated potassium channel in the vascular response to excess salt intake. PMID:19738156

Age-dependent MDPV-induced taste aversions and thermoregulation in adolescent and adult rats.

PubMed

Merluzzi, Andrew P; Hurwitz, Zachary E; Briscione, Maria A; Cobuzzi, Jennifer L; Wetzell, Bradley; Rice, Kenner C; Riley, Anthony L

2014-07-01

Adolescent rats are more sensitive to the rewarding and less sensitive to the aversive properties of various drugs of abuse than their adult counterparts. Given a nationwide increase in use of "bath salts," the present experiment employed the conditioned taste aversion procedure to assess the aversive effects of 3,4-methylenedioxypyrovalerone (MDPV; 0, 1.0, 1.8, or 3.2 mg/kg), a common constituent in "bath salts," in adult and adolescent rats. As similar drugs induce thermoregulatory changes in rats, temperature was recorded following MDPV administration to assess if thermoregulatory changes were related to taste aversion conditioning. Both age groups acquired taste aversions, although these aversions were weaker and developed at a slower rate in the adolescent subjects. Adolescents increased and adults decreased body temperature following MDPV administration with no correlation to aversions. The relative insensitivity of adolescents to the aversive effects of MDPV suggests that MDPV may confer an increased risk in this population. © 2013 Wiley Periodicals, Inc.

DSS 13 antenna monitor system. [Deep Space Network

NASA Technical Reports Server (NTRS)

Siev, B.; Bayergo, D.

1979-01-01

The development of a monitor system for the DSS 13 antenna is presented. The system checks for accumulator pressures, differential pressures, wind velocity, power supplies, fluid temperatures, and fluid levels. It was concluded that the system performed properly in high winds and correctly reported all malfunctions.

Eating high-fat chow enhances sensitization to the effects of methamphetamine on locomotion in rats

PubMed Central

McGuire, Blaine A.; Baladi, Michelle G.; France, Charles P.

2011-01-01

Eating high-fat chow can modify the effects of drugs acting directly or indirectly on dopamine systems and repeated intermittent drug administration can markedly increase sensitivity (i.e., sensitization) to the behavioral effects of indirect-acting dopamine receptor agonists (e.g., methamphetamine). This study examined whether eating high-fat chow alters the sensitivity of male Sprague Dawley rats to the locomotor stimulating effects of acute or repeated administration of methamphetamine. The acute effects of methamphetamine on locomotion were not different between rats (n=6/group) eating high-fat or standard chow for 1 or 4 weeks. Sensitivity to the effects of methamphetamine (0.1–10 mg/kg, i.p.) increased progressively across 4 once per week tests; this sensitization developed more rapidly and to a greater extent in rats eating high-fat chow as compared with rats eating standard chow. Thus, while eating high-fat chow does not appear to alter sensitivity of rats to acutely-administered methamphetamine, it significantly increases the sensitization that develops to repeated intermittent administration of methamphetamine. These data suggest that eating certain foods influences the development of sensitization to drugs acting on dopamine systems. PMID:21371470

Eating high-fat chow enhances sensitization to the effects of methamphetamine on locomotion in rats.

PubMed

McGuire, Blaine A; Baladi, Michelle G; France, Charles P

2011-05-11

Eating high-fat chow can modify the effects of drugs acting directly or indirectly on dopamine systems and repeated intermittent drug administration can markedly increase sensitivity (i.e., sensitization) to the behavioral effects of indirect-acting dopamine receptor agonists (e.g., methamphetamine). This study examined whether eating high-fat chow alters the sensitivity of male Sprague Dawley rats to the locomotor stimulating effects of acute or repeated administration of methamphetamine. The acute effects of methamphetamine on locomotion were not different between rats (n=6/group) eating high-fat or standard chow for 1 or 4 weeks. Sensitivity to the effects of methamphetamine (0.1-10mg/kg, i.p.) increased progressively across 4 once per week tests; this sensitization developed more rapidly and to a greater extent in rats eating high-fat chow as compared with rats eating standard chow. Thus, while eating high-fat chow does not appear to alter sensitivity of rats to acutely-administered methamphetamine, it significantly increases the sensitization that develops to repeated intermittent administration of methamphetamine. These data suggest that eating certain foods influences the development of sensitization to drugs acting on dopamine systems. Copyright © 2011 Elsevier B.V. All rights reserved.

On DSS Implementation in the Dynamic Model of the Digital Oil field

NASA Astrophysics Data System (ADS)

Korovin, Iakov S.; Khisamutdinov, Maksim V.; Kalyaev, Anatoly I.

2018-02-01

Decision support systems (DSS), especially based on the artificial intelligence (AI) techniques are been widely applied in different domains nowadays. In the paper we depict an approach of implementing DSS in to Digital Oil Field (DOF) dynamic model structure in order to reduce the human factor influence, considering the automation of all production processes to be the DOF model clue element. As the basic tool of data handling we propose the hybrid application on artificial neural networks and evolutional algorithms.

The Arabidopsis cax3 mutants display altered salt tolerance, pH sensitivity and reduced plasma membrane H+-ATPase activity.

PubMed

Zhao, Jian; Barkla, Bronwyn J; Marshall, Joy; Pittman, Jon K; Hirschi, Kendal D

2008-02-01

Perturbing CAX1, an Arabidopsis vacuolar H+/Ca2+ antiporter, and the related vacuolar transporter CAX3, has been previously shown to cause severe growth defects; however, the specific function of CAX3 has remained elusive. Here, we describe plant phenotypes that are shared among cax1 and cax3 including an increased sensitivity to both abscisic acid (ABA) and sugar during germination, and an increased tolerance to ethylene during early seedling development. We have also identified phenotypes unique to cax3, namely salt, lithium and low pH sensitivity. We used biochemical measurements to ascribe these cax3 sensitivities to a reduction in vacuolar H+/Ca2+ transport during salt stress and decreased plasma membrane H+-ATPase activity. These findings catalog an array of CAX phenotypes and assign a specific role for CAX3 in response to salt tolerance.

Effects of arachidonic acid intake on inflammatory reactions in dextran sodium sulphate-induced colitis in rats.

PubMed

Naito, Yukiko; Ji, Xu; Tachibana, Shigehiro; Aoki, Satoko; Furuya, Mami; Tazura, Yoshiyuki; Miyazawa, Daisuke; Harauma, Akiko; Moriguchi, Toru; Nagata, Tomoko; Iwai, Naoharu; Ohara, Naoki

2015-09-14

The aim of this study was to investigate the effects of the administration of oral arachidonic acid (AA) in rats with or without dextran sulphate sodium (DSS)-induced inflammatory bowel disease. Male Wistar rats were administered AA at 0, 5, 35 or 240 mg/kg daily by gavage for 8 weeks. Inflammatory bowel disease was induced by replacing drinking water with 3 % DSS solution during the last 7 d of the AA dosing period. These animals passed loose stools, diarrhoea and red-stained faeces. Cyclo-oxygenase-2 concentration and myeloperoxidase activity in the colonic tissue were significantly increased in the animals given AA at 240 mg/kg compared with the animals given AA at 0 mg/kg. Thromboxane B2 concentration in the medium of cultured colonic mucosae isolated from these groups was found to be dose-dependently increased by AA, and the increase was significant at 35 and 240 mg/kg. Leukotriene B4 concentration was also significantly increased and saturated at 5 mg/kg. In addition, AA at 240 mg/kg promoted DSS-induced colonic mucosal oedema with macrophage infiltration. In contrast, administration of AA for 8 weeks, even at 240 mg/kg, showed no effects on the normal rats. These results suggest that in rats with bowel disease AA metabolism is affected by oral AA, even at 5 mg/kg per d, and that excessive AA may aggravate inflammation, whereas AA shows no effects in rats without inflammatory bowel disease.

AOM/DSS Model of Colitis-Associated Cancer

PubMed Central

Parang, Bobak; Barret, Caitlyn W.; Williams, Christopher S.

2016-01-01

Summary Our understanding of colitis-associated carcinoma (CAC) has benefited substantially from mouse models that faithfully recapitulate human CAC. Chemical models, in particular, have enabled fast and efficient analysis of genetic and environmental modulators of CAC without the added requirement of time-intensive genetic crossings. Here we describe the Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) mouse model of inflammatory colorectal cancer. PMID:27246042

Deviance sensitivity in the auditory cortex of freely moving rats

PubMed Central

2018-01-01

Deviance sensitivity is the specific response to a surprising stimulus, one that violates expectations set by the past stimulation stream. In audition, deviance sensitivity is often conflated with stimulus-specific adaptation (SSA), the decrease in responses to a common stimulus that only partially generalizes to other, rare stimuli. SSA is usually measured using oddball sequences, where a common (standard) tone and a rare (deviant) tone are randomly intermixed. However, the larger responses to a tone when deviant does not necessarily represent deviance sensitivity. Deviance sensitivity is commonly tested using a control sequence in which many different tones serve as the standard, eliminating the expectations set by the standard ('deviant among many standards'). When the response to a tone when deviant (against a single standard) is larger than the responses to the same tone in the control sequence, it is concluded that true deviance sensitivity occurs. In primary auditory cortex of anesthetized rats, responses to deviants and to the same tones in the control condition are comparable in size. We recorded local field potentials and multiunit activity from the auditory cortex of awake, freely moving rats, implanted with 32-channel drivable microelectrode arrays and using telemetry. We observed highly significant SSA in the awake state. Moreover, the responses to a tone when deviant were significantly larger than the responses to the same tone in the control condition. These results establish the presence of true deviance sensitivity in primary auditory cortex in awake rats. PMID:29874246

The Effects of Difumarate Salt S-15176 after Spinal Cord Injury in Rats

PubMed Central

Tunçdemir, Matem; Kelten, Bilal; Akdemir, Osman; Karaoğlan, Alper; Taşdemiroğlu, Erol

2015-01-01

Objective In the present study we analyzed neuroprotective and antiapoptotic effect of the difumarate salt S-15176, as an anti-ischemic, an antioxidant and a stabilizer of mitochondrial membrane in secondary damage following spinal cord injury (SCI) in a rat model. Methods Three groups were performed with 30 Wistar rats; control (1), trauma (2), and a trauma+S-15176 (10 mg/kg i.p., dimethyl sulfoxide) treatment (3). SCI was performed at the thoracic level using the weight-drop technique. Spinal cord tissues were collected following intracardiac perfusion in 3rd and 7th days of posttrauma. Hematoxylin and eosin staining for histopatology, terminal deoxynucleotidyl transferase dUTP nick end labeling assay for apoptotic cells and immunohistochemistry for proapoptotic cytochrome-c, Bax and caspase 9 were performed to all groups. Functional recovery test were applied to each group in 3rd and 7th days following SCI. Results In trauma group, edematous regions, diffuse hemorrhage, necrosis, leukocyte infiltration and severe degeneration in motor neurons were observed prominently in gray matter. The number of apoptotic cells was significantly higher (p<0.05) than control group. In the S-15176-treated groups, apoptotic cell number in 3rd and 7th days (p<0.001), also cytochrome-c (p<0.001), Bax (p<0.001) and caspase 9 immunoreactive cells (p<0.001) were significantly decreased in number compared to trauma groups. Hemorrhage and edema in the focal areas were also noticed in gray matter of treatment groups. Results of the locomotor test were significantly increased in treatment group (p<0.05) when compared to trauma groups. Conclusion We suggest that difumarate salt S-15176 prevents mitochondrial pathways of apoptosis and protects spinal cord from secondary injury and helps to preserve motor function following SCI in rats. PMID:26180614

EFFECTS OF CHRONIC EXCESS SALT FEEDING

PubMed Central

Dahl, Lewis K.; Heine, Martha

1961-01-01

Female rats were fed diets containing either excess sea salt or excess sodium chloride for periods up to 14 months. The hypertension produced by sea salt was more pronounced than that caused by sodium chloride alone, although the average amount of sodium chloride contained in the sea salt feeding was slightly less. The ions involved in this incremental effect of sea salt were not identified. PMID:13719314

Optogenetic Inhibition of Ventral Pallidum Neurons Impairs Context-Driven Salt Seeking.

PubMed

Chang, Stephen E; Smedley, Elizabeth B; Stansfield, Katherine J; Stott, Jeffrey J; Smith, Kyle S

2017-06-07

Salt appetite, in which animals can immediately seek out salt when under a novel state of sodium deprivation, is a classic example of how homeostatic systems interface with learned associations to produce an on-the-fly updating of motivated behavior. Neural activity in the ventral pallidum (VP) has been shown to encode changes in the value of salt under such conditions, both the value of salt itself (Tindell et al., 2006) and the motivational value of its predictive cues (Tindell et al., 2009; Robinson and Berridge, 2013). However, it is not known whether the VP is necessary for salt appetite in terms of seeking out salt or consuming salt following sodium depletion. Here, we used a conditioned place-preference procedure to investigate the effects of optogenetically inhibiting the VP on context-driven salt seeking and the consumption of salt following deprivation. Male rats learned to associate one context with sucrose and another context with less-desirable salt. Following sodium depletion, and in the absence of either sucrose or salt, we found that inhibiting the VP selectively reduced the elevation in time spent in the salt-paired context. VP inhibition had minimal effects on the consumption of salt once it was made available. To our knowledge, this is the first evidence that the VP or any brain region is necessary for the ability to use contextual cues to guide salt seeking. These results highlight a dissociation between deficit-driven reward seeking and reward consumption to replenish those deficits, with the former process being particularly sensitive to on-line VP activity. SIGNIFICANCE STATEMENT Salt appetite, in which rats will immediately seek out a once-undesirable concentrated salt solution after being depleted of bodily sodium despite never having tasted salt as a positive reward, is a phenomenon showing how animals can update their motivational goals without any new learning or conditioning. This salt-seeking behavior is also observed when the animal

Soy protein supports cardiovascular health by downregulating hydroxymethylglutaryl-coenzyme A reductase and sterol regulatory element-binding protein-2 and increasing antioxidant enzyme activity in rats with dextran sodium sulfate-induced mild systemic inflammation.

PubMed

Marsh, Tanya G; Straub, Rachel K; Villalobos, Fatima; Hong, Mee Young

2011-12-01

Animal and human studies have indicated that the presence of soy in the diet improves cardiovascular health. Inflammation plays a pivotal role in the progression of cardiovascular disease (CVD). However, little is known about how dextran sodium sulfate (DSS)-induced systemic inflammation impacts overall heart health and, correspondingly, how soy protein modulates risk of CVD development in DSS-induced systemic inflammation. We hypothesized that soy protein-fed rats would have a lower risk of CVD by beneficial alteration of gene expression involving lipid metabolism and antioxidant capacity in DSS-induced systemic inflammation. Forty Sprague-Dawley rats were divided into 4 groups: casein, casein + DSS, soy protein, and soy protein + DSS. After 26 days, inflammation was induced in one group from each diet by incorporating 3% DSS in drinking water for 48 hours. Soy protein-fed rats had lower final body weights (P = .010), epididymal fat weights (P = .049), total cholesterol (P < .001), and low-density lipoprotein cholesterol (P < .001). In regard to gene expression, soy protein-fed rats had lower sterol regulatory element-binding protein-2 (P = .032) and hydroxymethylglutaryl-coenzyme A reductase (P = .028) levels and higher low-density lipoprotein receptor levels (P = .036). Antioxidant enzyme activity of superoxide dismutase and catalase was higher among the soy protein groups (P = .037 and P = .002, respectively). These results suggest that soy protein positively influences cardiovascular health by regulating serum lipids through modified expression of sterol regulatory element-binding protein-2 and its downstream genes (ie, hydroxymethylglutaryl-coenzyme A reductase and low-density lipoprotein receptor) and by promoting the antioxidant enzyme activity of superoxide dismutase and catalase. Copyright © 2011 Elsevier Inc. All rights reserved.

Platinum salt sensitivity in refinery workers: incidence and effects of smoking and exposure.

PubMed Central

Calverley, A E; Rees, D; Dowdeswell, R J; Linnett, P J; Kielkowski, D

1995-01-01

OBJECTIVE--To measure the incidence of platinum salt sensitivity (PSS) in refinery workers and examine the influence of cigarette smoking and exposure to platinum salts on sensitisation. DESIGN--A prospective cohort study with examination of workers at quarterly intervals for 18 months, and again at 24 months. SETTING--A South African primary platinum refinery. SUBJECTS--78 new recruits, selected by the refinery's usual procedure, without apparent atopy and in good respiratory health. RESULTS--After 24 months 32 (41%) subjects had been diagnosed PSS and were subsequently medically separated. Twenty two (28%) cases were confirmed by positive skin prick test to platinum salts, 10 (13%) cases were symptomatic but skin prick negative. Incidence of cases per 100 person-months was 1.9 skin prick positive and 0.8 negative. Risk of sensitisation was about eight times greater for smokers than non-smokers, and six times greater for high exposure than low exposure. CONCLUSION--Smoking and intensity of exposure were definitely associated with development of PSS. Positive responses to platinum salt skin prick test had a 100% positive predictive value for symptoms and signs of PSS if exposure continued. PMID:7489056

Influence of aldosterone and salt or ouabain in a10 rat aorta smooth muscle cells.

PubMed

Schwerdt, Gerald; Frisch, Annett; Mildenberger, Sigrid; Hilgenfeld, Tim; Grossmann, Claudia; Gekle, Michael

2012-01-01

It is currently under debate whether aldosterone is able to induce fibrosis or whether it acts only as a cofactor under pathological conditions, e.g. as an elevated salt (NaCl) load. We tested the interaction of 10 nM aldosterone, 15 mM NaCl and 1 μM ouabain using rat aorta smooth muscle cells (A10) with respect to the following parameters: necrosis, apoptosis, glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase activity, glutathione (GSH) content, collagen and fibronectin homeostasis and intracellular calcium distribution. Necrosis rates were increased after 48 h of incubation with aldosterone, salt or ouabain and in the combination of aldosterone and salt or ouabain. Apoptosis rates were decreased. A reduced defense capacity against oxidative stress was mirrored in the decreased G6PD activity and GSH content. Collagen III or fibronectin synthesis rates were unchanged, but gelatinase activity was increased resulting in a decreased media collagen III and fibronectin content. Calcium stores were increased by aldosterone in combination with ouabain. Aldosterone and salt per se can lead to cell injury that is aggravated in combination or with cardiotonic steroids. In cooperation with other vascular cells, this can generate a permissive milieu enabling aldosterone or salt to promote more extensive vascular injury. Copyright © 2012 S. Karger AG, Basel.

The Receptor-Like Kinase SIT1 Mediates Salt Sensitivity by Activating MAPK3/6 and Regulating Ethylene Homeostasis in Rice[C][W

PubMed Central

Li, Chen-Hui; Wang, Geng; Zhao, Ji-Long; Zhang, Li-Qing; Ai, Lian-Feng; Han, Yong-Feng; Sun, Da-Ye; Zhang, Sheng-Wei; Sun, Ying

2014-01-01

High salinity causes growth inhibition and shoot bleaching in plants that do not tolerate high salt (glycophytes), including most crops. The molecules affected directly by salt and linking the extracellular stimulus to intracellular responses remain largely unknown. Here, we demonstrate that rice (Oryza sativa) Salt Intolerance 1 (SIT1), a lectin receptor-like kinase expressed mainly in root epidermal cells, mediates salt sensitivity. NaCl rapidly activates SIT1, and in the presence of salt, as SIT1 kinase activity increased, plant survival decreased. Rice MPK3 and MPK6 function as the downstream effectors of SIT1. SIT1 phosphorylates MPK3 and 6, and their activation by salt requires SIT1. SIT1 mediates ethylene production and salt-induced ethylene signaling. SIT1 promotes accumulation of reactive oxygen species (ROS), leading to growth inhibition and plant death under salt stress, which occurred in an MPK3/6- and ethylene signaling-dependent manner in Arabidopsis thaliana. Our findings demonstrate the existence of a SIT1-MPK3/6 cascade that mediates salt sensitivity by affecting ROS and ethylene homeostasis and signaling. These results provide important information for engineering salt-tolerant crops. PMID:24907341

THE ROLE OF LYMPHOCYTES IN THE SENSITIZATION OF RATS TO RENAL HOMOGRAFTS

PubMed Central

Strober, S.; Gowans, J. L.

1965-01-01

In order to study the role of blood-borne small lymphocytes in the sensitization of rats to renal homografts 2 techniques for the perfusion of isolated rat kidneys were employed: (a) the in vitro perfusion of kidneys with thoracic duct cells suspended in either an artificial medium or in blood; the perfusates were then injected into rats syngeneic with the lymphocyte donors; (b) the in vivo perfusion of kidneys with blood issuing from the femoral artery and returning to the femoral vein of living rats. The degree of sensitization conferred on the recipients by the perfusates was assessed by applying a skin homograft from the kidney donor and scoring the epithelial necrosis at 6 days. The in vitro experiments indicated that parental strain thoracic duct cells, which had passed through an F1 hybrid kidney could confer upon a parental rat sensitivity to an F1 skin graft. Several perfusions with radioactively labelled lymphocytes showed that the injected cells migrated to the lymph nodes and spleen of the recipients Labelled large pyroninophilic cells were occasionally seen in the spleen and lymph nodes of recipients, and it was suggested that these had arisen from the injected cells. Although the in vitro perfusions with blood indicated that renal homografts might sensitize their hosts within 1 hour, the in vivo perfusions suggested that about 5 to 12 hours were required. The more rapid sensitization in vitro was possibly due to the more frequent opportunity for contact between lymphocytes and kidney vascular endothelium which was afforded by the conditions in vitro. PMID:14316949

Comparative Evaluation between Sulfasalazine Alone and in Combination with Herbal Medicine on DSS-Induced Ulcerative Colitis Mice

PubMed Central

Shin, Mi-Rae; Kim, Kyeong Jo; Kim, Soo Hyun; Kim, Su Ji

2017-01-01

The present study aimed to investigate the comparative evaluation of pharmacological efficacy between sulfasalazine alone and sulfasalazine in combination with herbal medicine on dextran sodium sulfate- (DSS-) induced UC in mice. Balb/c mice received 5% DSS in drinking water for 7 days to induce colitis. Animals were divided into five groups (n = 9): Group I (normal group), Group II (DSS control group), Group III (DSS + sulfasalazine (30 mg/kg)), Group IV (DSS + sulfasalazine (60 mg/kg)), and Group V (DSS + sulfasalazine (30 mg/kg) + Cinnamomi Cortex and Bupleuri Radix mixture (30 mg/kg) (SCB)). Colonic pathological changes were analyzed using hematoxyline/eosin staining. The antioxidant, inflammatory, and apoptotic protein levels were determined using western blotting. SCB supplementation, as well as sulfasalazine, suppressed colonic length and mucosal inflammatory infiltration. In addition, SCB treatment significantly reduced the expression of proinflammatory signaling molecules through suppression of both mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways and prevented the apoptosis of the colon. Moreover, SCB administration significantly led to the upregulation of antioxidant enzymes including SOD and catalase. Taken together, SCB treatment might offer a better treatment for human UC than sulfasalazine alone or may be useful as an alternative therapeutic strategy against UC, without any evidence of side effects. PMID:29018816

Excessively low salt diet damages the heart through activation of cardiac (pro) renin receptor, renin-angiotensin-aldosterone, and sympatho-adrenal systems in spontaneously hypertensive rats.

PubMed

Okamoto, Chihiro; Hayakawa, Yuka; Aoyama, Takuma; Komaki, Hisaaki; Minatoguchi, Shingo; Iwasa, Masamitsu; Yamada, Yoshihisa; Kanamori, Hiromitsu; Kawasaki, Masanori; Nishigaki, Kazuhiko; Mikami, Atsushi; Minatoguchi, Shinya

2017-01-01

A high salt intake causes hypertension and leads to cardiovascular disease. Therefore, a low salt diet is now recommended to prevent hypertension and cardiovascular disease. However, it is still unknown whether an excessively low salt diet is beneficial or harmful for the heart. Wistar Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) received normal salt chow (0.9% salt diet) and excessively low salt chow (0.01% salt diet referred to as saltless diet) for 8 weeks from 8 to 16 weeks of age. The effects of the excessively low salt diet on the cardiac (pro) renin receptor, renin-angiotensin-aldosterone, and sympatho-adrenal systems were investigated. The excessively low salt diet did not affect the systolic blood pressure but significantly increased the heart rate both in WKYs and SHRs. The excessively low salt diet significantly elevated plasma renin activity, plasma angiotensin I, II and aldosterone concentrations, and plasma noradrenaline and adrenaline concentrations both in WKYs and SHRs. Cardiac expressions of renin, prorenin, (P)RR, angiotensinogen, and angiotensin II AT1 receptor and phosphorylated (p)-ERK1/2, p-HSP27, p-38MAPK, and TGF-ß1 were significantly enhanced by the excessively low salt diet in both WKYs and SHRs. The excessively low salt diet accelerated cardiac interstitial and perivascular fibrosis and increased the cardiomyocyte size and interventricular septum thickness in WKYs and SHRs but the extent was greater in SHRs. An excessively low salt diet damages the heart through activation of plasma renin-angiotensin-aldosterone and sympatho-adrenal systems and activation of cardiac (P)RR and angiotensin II AT1 receptor and their downstream signals both in WKYs and SHRs.

Berberine promotes recovery of colitis and inhibits inflammatory responses in colonic macrophages and epithelial cells in DSS-treated mice

PubMed Central

Wang, Lihong; Shi, Yan; Cao, Hanwei; Liu, Liping; Washington, M. Kay; Chaturvedi, Rupesh; Israel, Dawn A.; Cao, Hailong; Wang, Bangmao; Peek, Richard M.; Wilson, Keith T.; Polk, D. Brent

2012-01-01

Inflammatory bowel disease (IBD) results from dysregulation of intestinal mucosal immune responses to microflora in genetically susceptible hosts. A major challenge for IBD research is to develop new strategies for treating this disease. Berberine, an alkaloid derived from plants, is an alternative medicine for treating bacterial diarrhea and intestinal parasite infections. Recent studies suggest that berberine exerts several other beneficial effects, including inducing anti-inflammatory responses. This study determined the effect of berberine on treating dextran sulfate sodium (DSS)-induced intestinal injury and colitis in mice. Berberine was administered through gavage to mice with established DSS-induced intestinal injury and colitis. Clinical parameters, intestinal integrity, proinflammatory cytokine production, and signaling pathways in colonic macrophages and epithelial cells were determined. Berberine ameliorated DSS-induced body weight loss, myeloperoxidase activity, shortening of the colon, injury, and inflammation scores. DSS-upregulated proinflammatory cytokine levels in the colon, including TNF, IFN-γ, KC, and IL-17 were reduced by berberine. Berberine decreased DSS-induced disruption of barrier function and apoptosis in the colon epithelium. Furthermore, berberine inhibited proinflammatory cytokine production in colonic macrophages and epithelial cells in DSS-treated mice and promoted apoptosis of colonic macrophages. Activation of signaling pathways involved in stimulation of proinflammatory cytokine production, including MAPK and NF-κB, in colonic macrophages and epithelial cells from DSS-treated mice was decreased by berberine. In summary, berberine promotes recovery of DSS-induced colitis and exerts inhibitory effects on proinflammatory responses in colonic macrophages and epithelial cells. Thus berberine may represent a new therapeutic approach for treating gastrointestinal inflammatory disorders. PMID:22173918

Design and implementation of a beam-waveguide mirror control system for vernier pointing of the DSS-13 antenna

NASA Technical Reports Server (NTRS)

Alvarez, L. S.; Moore, M.; Veruttipong, W.; Andres, E.

1994-01-01

The design and implementation of an antenna beam-waveguide (BWG) mirror position control system at the DSS-13 34-m antenna is presented. While it has several potential applications, a positioner on the last flat-plate BWG mirror (M6) at DSS 13 is installed to demonstrate the conical scan (conscan) angle-tracking technique at the Ka-band (32-GHz) operating frequency. Radio frequency (RF) beam-scanning predictions for the M6 mirror, computed from a diffraction analysis, are presented. From these predictions, position control system requirements are then derived. The final mechanical positioner and servo system designs, as implemented at DSS 13, are illustrated with detailed design descriptions given in the appendices. Preliminary measurements of antenna Ka-band beam scan versus M6 mirror tilt made at DSS 13 in December 1993 are presented. After reduction, the initial measurements are shown to be in agreement with the RF predicts. Plans for preliminary conscan experimentation at DSS 13 are summarized.

Comparison of two models of inflammatory bowel disease in rats.

PubMed

Catana, Cristina Sorina; Magdas, Cristian; Tabaran, Flaviu Alexandru; Crăciun, Elena Cristina; Deak, Georgiana; Magdaş, Virginia Ana; Cozma, Vasile; Gherman, Călin Mircea; Berindan-Neagoe, Ioana; Dumitraşcu, Dan Lucian

2018-03-26

There is a need for experimental animal models for inflammatory bowel diseases (IBD), but no proposed model has been unanimously accepted. The aim of this study was to develop 2 affordable models of IBD in rats and to compare them. We produced IBD in rats using either dextran sodium sulfate (DSS) or 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The requirements for experimental models were: a predictable clinical course, histopathology and inflammation similar to human ulcerative colitis (UC) and Crohn's disease (CD). The effect of acute administration of DSS and TNBS on oxidative stress (as measured by the assessment of glutathione peroxidase - GPx) was verified. The activity of whole blood GPx was measured using a commercially available Randox kit (Crumlin, UK). The administration of DSS increased GPx activity compared to the control and TNBS-treated groups, but not to a statistically significant degree. Histological examination of the colonic mucosa following the administration of DSS showed multifocal erosions with minimal to mild inflammatory infiltrate, mainly by polymorphonuclear cells (PMN), lymphocytes and plasma cells. For TNBS-induced colitis, the histological changes manifested as multifocal areas of ulcerative colitis with mild to severe inflammatory infiltrate. Whole blood GPx values displayed a direct dependence on the chemical agent used. Our results show a correlation between histopathology, proinflammatory state and oxidative stress. The experimental DSSor TNBS-induced bowel inflammation used in this study corresponds to human IBD and is reproducible with characteristics indicative of acute inflammation in the case of the protocols mentioned.

Nicotine protects against DSS colitis through regulating microRNA-124 and STAT3.

PubMed

Qin, Zhen; Wan, Jing-Jing; Sun, Yang; Wu, Tingyu; Wang, Peng-Yuan; Du, Peng; Su, Ding-Feng; Yang, Yili; Liu, Xia

2017-02-01

Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis, the underlying mechanisms remain not well understood. Our previous finding that nicotine inhibits inflammatory responses through inducing miR-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine against UC. Our present study found that miR-124 expression is upregulated in colon tissues from UC patients and DSS colitis mice. Nicotine treatment further augmented miR-124 expression in lymphocytes isolated from human ulcerative colonic mucosa and ulcerative colon tissues from DSS mice, both in infiltrated lymphocytes and epithelial cells. Moreover, knockdown of miR-124 significantly diminished the beneficial effect of nicotine on murine colitis and IL-6-treated Caco-2 colon epithelial cells. Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6 treated Caco-2 cells and Jurkat human T lymphocytes, in which miR-124 knockdown led to increased activation of STAT3. Blocking STAT3 activity alone is beneficial for DSS colitis and also abolished nicotine's protective effect in this model. These data indicate that nicotine exerts its protective action in UC through inducing miR-124 and inhibiting STAT3, and suggest that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC. Nicotine upregulates miR-124 expression in ulcerative colon tissues and cells. MiR-124 is required for the protective role of nicotine in DSS colitis mice and epithelial cells. The protective effect of nicotine in murine DSS colitis depends on blocking STAT3 activation. MiR-124 mediates the inhibitory role of nicotine on STAT3/p-STAT3. Targeting miR-124 and STAT3 represents a novel approach for treating ulcerative colitis.

Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China: a dietary intervention study.

PubMed

Chen, Jing; Gu, Dongfeng; Huang, Jianfeng; Rao, Dabeeru C; Jaquish, Cashell E; Hixson, James E; Chen, Chung-Shiuan; Chen, Jichun; Lu, Fanghong; Hu, Dongsheng; Rice, Treva; Kelly, Tanika N; Hamm, L Lee; Whelton, Paul K; He, Jiang

2009-03-07

Since insulin resistance is thought to be the underlying mechanism for metabolic syndrome, affected individuals might be sensitive to a dietary sodium intervention. We aimed to examine the association between metabolic syndrome and salt sensitivity of blood pressure. 1906 Chinese participants without diabetes, aged 16 years or more, were selected to receive a low-sodium diet (51.3 mmol per day) for 7 days followed by a high-sodium diet (307.8 mmol per day) for an additional 7 days. Participants were excluded from the analysis if metabolic risk factor information was missing or if they did not complete their dietary interventions. Blood pressure was measured at baseline and on days 2, 5, 6, and 7 of each intervention. Metabolic syndrome was defined as the presence of three or more of: abdominal obesity, raised blood pressure, high triglyceride concentration, low HDL cholesterol, or high glucose. High salt sensitivity was defined as a decrease in mean arterial blood pressure of more than 5 mm Hg during low-sodium or an increase of more than 5 mm Hg during high-sodium intervention. This study is registered with ClinicalTrials.gov, number NCT00721721. Of the 1881 participants with information regarding metabolic syndrome, 283 had metabolic syndrome. 1853 participants completed the low-sodium diet and 1845 completed the high-sodium diet. Multivariable-adjusted mean changes in blood pressure were significantly greater in participants with metabolic syndrome than in those without on both low-sodium and high-sodium diets (p<0.0001 for all comparisons). Additionally, risk of salt sensitivity rose with increasing numbers of risk factors for metabolic syndrome. Compared with those with no risk factors, participants with four or five had a 3.54-fold increased odds (95% CI 2.05-6.11) of high salt-sensitivity during the low-sodium and a 3.13-fold increased odds (1.80-5.43) of high salt-sensitivity during the high-sodium intervention. These results suggest that metabolic syndrome

Angelica acutiloba Kitagawa Extract Attenuates DSS-Induced Murine Colitis

PubMed Central

Jang, Jong-Chan; Lee, Kang Min

2016-01-01

We examined the protective effects of Angelica acutiloba Kitagawa (AAK) extract on a murine model of acute experimental colitis. Colitis was induced by 4% dextran sulfate sodium (DSS) in the drinking water of male C57BL/6 mice, for 7 consecutive days. Oral administration of AAK extract (500 mg/kg/day) significantly alleviated DSS-induced symptoms such as anorexia, weight loss, events of diarrhea or bloody stools, and colon shortening. Histological damage was also ameliorated, as evidenced by the architectural preservation and suppression of inflammatory cell infiltration in colonic samples. Treatment improved the colonic mRNA expression of different inflammatory markers: cytokines, inducible enzymes, matrix metalloproteinases, and tight junction-related proteins. In the isolated serum, IgE levels were downregulated. Collectively, these findings indicate the therapeutic potentials of AAK as an effective complementary or alternative modality for the treatment of ulcerative colitis. PMID:27293323

A cytochrome P450, OsDSS1, is involved in growth and drought stress responses in rice (Oryza sativa L.).

PubMed

Tamiru, Muluneh; Undan, Jerwin R; Takagi, Hiroki; Abe, Akira; Yoshida, Kakoto; Undan, Jesusa Q; Natsume, Satoshi; Uemura, Aiko; Saitoh, Hiromasa; Matsumura, Hideo; Urasaki, Naoya; Yokota, Takao; Terauchi, Ryohei

2015-05-01

Cytochrome P450s are among the largest protein coding gene families in plant genomes. However, majority of the genes remain uncharacterized. Here, we report the characterization of dss1, a rice mutant showing dwarfism and reduced grain size. The dss1 phenotype is caused by a non-synonymous point mutation we identified in DSS1, which is member of a P450 gene cluster located on rice chromosome 3 and corresponds to the previously reported CYP96B4/SD37 gene. Phenotypes of several dwarf mutants characterized in rice are associated with defects in the biosynthesis or perception of the phytohormones gibberellins (GAs) and brassinosteroids (BRs). However, both GA and BR failed to rescue the dss1 phenotype. Hormone profiling revealed the accumulation of abscisic acid (ABA) and ABA metabolites, as well as significant reductions in GA19 and GA53 levels, precursors of the bioactive GA1, in the mutant. The dss1 contents of cytokinin and auxins were not significantly different from wild-type plants. Consistent with the accumulation of ABA and metabolites, germination and early growth was delayed in dss1, which also exhibited an enhanced tolerance to drought. Additionally, expressions of members of the DSS1/CYP96B gene cluster were regulated by drought stress and exogenous ABA. RNA-seq-based transcriptome profiling revealed, among others, that cell wall-related genes and genes involved in lipid metabolism were up- and down-regulated in dss1, respectively. Taken together, these findings suggest that DSS1 mediates growth and stress responses in rice by fine-tuning GA-to-ABA balance, and might as well play a role in lipid metabolism.

Carvacrol exhibits anti-oxidant and anti-inflammatory effects against 1, 2-dimethyl hydrazine plus dextran sodium sulfate induced inflammation associated carcinogenicity in the colon of Fischer 344 rats.

PubMed

Arigesavan, Kaninathan; Sudhandiran, Ganapasam

2015-05-29

Chronic inflammation is one of the remarkable etiologic factors for various human ailments including cancer. The well known hypothesis is that persistent inflammation in colon can increase the risk of colorectal cancer (CRC). In this study, a pharmacological evaluation of carvacrol, a phenolic monoterpene constituent of essential oils produced from aromatic plant Oreganum vulgarea sp. on colitis associated colon cancer (CACC) induced by 1,2 Dimethylhydrazine (DMH) and dextran sodium sulfate (DSS) in male Fischer 344 rat model was studied. F344 rats were given three subcutaneous injections of DMH (40 mg/kg body wt) in the first week and were given free access to drinking water containing 1% DSS for the next one week followed by 7-14 days of water as three cycles. Carvacrol was administrated before and after tumor induction at a concentration of 50 mg/kg body weight (o.p). Carvacrol treated groups promotes the endogenous antioxidant system and suppress the inflammation in DMH/DSS induced animals. An increased antioxidant status and restoration of histological lesions in the inflamed colonic mucosa was observed in carvacrol treated rats. This effect was confirmed biochemically by reducing free-radical accumulation and suppressing expression of pro-inflammatory mediators. In this study, Carvacrol significantly increased the anti-oxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) glutathione (GSH) levels and reduced lipid peroxides (LPO), myeloperoxidase (MPO) and nitric oxide (NO) as compared to DMH/DSS induced rats. These dramatic changes facilitate the suppression of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), and interleukin-1 beta (IL-1β) in CACC induced rats. Taken together, these findings suggest that Carvacrol may play a beneficial role in DMH/DSS induced experimental rat model and serve as an excellent dietary antioxidant as well as anti-inflammatory agent. It may represent novel therapeutic interventions

Xilei San Ameliorates Experimental Colitis in Rats by Selectively Degrading Proinflammatory Mediators and Promoting Mucosal Repair

PubMed Central

Hori, Kazutoshi; Wang, Shenglan; Kogure, Yoko; Fukunaga, Ken; Kashiwamura, Shinichiro; Yamamoto, Satoshi; Nakamura, Shiro; Li, Junxiang; Miwa, Hiroto; Noguchi, Koichi

2014-01-01

Xilei san (XLS), a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC). The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS) to the rats' drinking water for 7 days. XLS was administered daily by retention enema from day 2 to day 7; the rats were sacrificed on day 8. The colon tissues were obtained for further experiments. A histological damage score and the activity of tissue myeloperoxidase were used to evaluate the severity of the colitis. The colonic cytokine levels were detected in a suspension array, and epithelial proliferation was assessed using Ki-67 immunohistochemistry. Intrarectal administration of XLS attenuated the DSS-induced colitis, as evidenced by a reduction in both the histological damage score and myeloperoxidase activity. It also decreased the levels of proinflammatory cytokines, but increased the mucosal repair-related cytokines. In addition, the epithelial Ki-67 expression was upregulated by XLS. These results suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory mediators and promoting mucosal repair. XLS could be a potential topical treatment for human UC. PMID:25120575

Xilei san ameliorates experimental colitis in rats by selectively degrading proinflammatory mediators and promoting mucosal repair.

PubMed

Hao, Yongbiao; Nagase, Kazuko; Hori, Kazutoshi; Wang, Shenglan; Kogure, Yoko; Fukunaga, Ken; Kashiwamura, Shinichiro; Yamamoto, Satoshi; Nakamura, Shiro; Li, Junxiang; Miwa, Hiroto; Noguchi, Koichi; Dai, Yi

2014-01-01

Xilei san (XLS), a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC). The present experiments were conducted to assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS) to the rats' drinking water for 7 days. XLS was administered daily by retention enema from day 2 to day 7; the rats were sacrificed on day 8. The colon tissues were obtained for further experiments. A histological damage score and the activity of tissue myeloperoxidase were used to evaluate the severity of the colitis. The colonic cytokine levels were detected in a suspension array, and epithelial proliferation was assessed using Ki-67 immunohistochemistry. Intrarectal administration of XLS attenuated the DSS-induced colitis, as evidenced by a reduction in both the histological damage score and myeloperoxidase activity. It also decreased the levels of proinflammatory cytokines, but increased the mucosal repair-related cytokines. In addition, the epithelial Ki-67 expression was upregulated by XLS. These results suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory mediators and promoting mucosal repair. XLS could be a potential topical treatment for human UC.

Increased sensitivity to the acute effects of MDMA ("ecstasy") in female rats.

PubMed

Palenicek, T; Votava, M; Bubenikova, V; Horacek, J

2005-11-15

Behavioral effects of +/-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are relatively well described in humans as well as in animals. However, little is known about gender differences to the effects of MDMA. The aim of our study was to evaluate gender differences in stimulant effects of MDMA (2.5, 5.0, and 10.0 mg/kg subcutaneously (s.c.)) in male and female Wistar rats. We have used three behavioral methods (activity cage, open field, and elevated plus-maze) each describing a different pattern of spontaneous behavior. In the activity cage, 30 min after the MDMA administration, horizontal and vertical locomotor activities were registered for a period of 3 min. In the open field test rats were placed into an arena 15 min after drug treatment and locomotor activity was registered for a period of 30 min. Finally, in the elevated plus-maze test, rats were given MDMA 30 min prior to measurements and subsequently they were tested in the maze for a period of 5 min. In our experiments we observed a dose-dependent locomotion-enhancing effect of MDMA both in male and female rats in both locomotor tests. Female rats were more sensitive to the locomotor-stimulating effect than males in both tests, suggesting higher sensitivity to the stimulatory effect of MDMA. Further on, MDMA increased thigmotaxis in female rats in the open field test and decreased "anxious-like" behavior in the elevated plus-maze in both genders. In conclusion, we observed higher sensitivity of females to the locomotor-stimulant effect of MDMA. Increased sensitivity of females to the behavioral effects of MDMA can be explained by increased reactivity of serotonergic and dopaminergic systems.

Early life stress sensitizes the renal and systemic sympathetic system in rats.

PubMed

Loria, Analia S; Brands, Michael W; Pollock, David M; Pollock, Jennifer S

2013-08-01

We hypothesized that maternal separation (MS), an early life stress model, induces a sensitization of the sympathetic system. To test this hypothesis, we evaluated the renal and systemic sympathetic system in 12- to 14-wk-old male control or MS rats with the following parameters: 1) effect of renal denervation on conscious renal filtration capacity, 2) norepinephrine (NE) content in key organs involved in blood pressure control, and 3) acute systemic pressor responses to adrenergic stimulation or ganglion blockade. MS was performed by separating pups from their mothers for 3 h/day from day 2 to 14; controls were nonhandled littermates. Glomerular filtration rate (GFR) was examined in renal denervated (DnX; within 2 wk) or sham rats using I¹²⁵-iothalamate plasma clearance. MS-DnX rats showed significantly increased GFR compared with MS-SHAM rats (3.8 ± 0.4 vs. 2.4 ± 0.2 ml/min, respectively, P < 0.05), whereas DnX had no effect in controls, indicating that renal nerves regulate GFR in MS rats. NE content was significantly increased in organ tissues from MS rats (P < 0.05, n = 6-8), suggesting a sensitization of the renal and systemic sympathetic system. Conscious MS rats displayed a significantly greater increase in mean arterial pressure (MAP) in response to NE (2 μg/kg ip) and a greater reduction in MAP in response to mecamylamine (2 mg/kg ip, P < 0.05, n = 4) monitored by telemetry, indicating that MS rats exhibit exaggerated responses to sympathetic stimulation. In conclusion, these data indicate that MS sensitizes the renal and systemic sympathetic system ultimately impairing blood pressure regulation.

Matrix metalloproteinase 9-induced increase in intestinal epithelial tight junction permeability contributes to the severity of experimental DSS colitis

PubMed Central

Nighot, Prashant; Al-Sadi, Rana; Guo, Shuhong; Watterson, D. Martin; Ma, Thomas

2015-01-01

Recent studies have implicated a pathogenic role for matrix metalloproteinases 9 (MMP-9) in inflammatory bowel disease. Although loss of epithelial barrier function has been shown to be a key pathogenic factor for the development of intestinal inflammation, the role of MMP-9 in intestinal barrier function remains unclear. The aim of this study was to investigate the role of MMP-9 in intestinal barrier function and intestinal inflammation. Wild-type (WT) and MMP-9−/− mice were subjected to experimental dextran sodium sulfate (DSS) colitis by administration of 3% DSS in drinking water for 7 days. The mouse colonic permeability was measured in vivo by recycling perfusion of the entire colon using fluorescently labeled dextran. The DSS-induced increase in the colonic permeability was accompanied by an increase in intestinal epithelial cell MMP-9 expression in WT mice. The DSS-induced increase in intestinal permeability and the severity of DSS colitis was found to be attenuated in MMP-9−/− mice. The colonic protein expression of myosin light chain kinase (MLCK) and phospho-MLC was found to be significantly increased after DSS administration in WT mice but not in MMP-9−/− mice. The DSS-induced increase in colonic permeability and colonic inflammation was attenuated in MLCK−/− mice and MLCK inhibitor ML-7-treated WT mice. The DSS-induced increase in colonic surface epithelial cell MLCK mRNA was abolished in MMP-9−/− mice. Lastly, increased MMP-9 protein expression was detected within the colonic surface epithelial cells in ulcerative colitis cases. These data suggest a role of MMP-9 in modulation of colonic epithelial permeability and inflammation via MLCK. PMID:26514773

DSS 13 frequency stability tests

NASA Technical Reports Server (NTRS)

Otoshi, T. Y.; Franco, M. M.

1987-01-01

In a previous article, the results of frequency stability tests at DSS 13 were presented in table form for tau = 1000 s for the test period May 1985 through March 1986. This article is a continuation of that initial report and presents specially selected Allan sigma (square root of variance) plots of each of the subsystem test previously reported. An additional result obtained from tests performed during July 1986 was included for completeness. The Allan sigma plots are useful in that frequency stability information is not only given for tau = 1000 s, but for tau values in the regions of 1, 100, 500, and 2000 s as well.

Attenuation of colonic inflammation by partial replacement of dietary linoleic acid with α-linolenic acid in a rat model of inflammatory bowel disease.

PubMed

Tyagi, Anupama; Kumar, Uday; Reddy, Suryam; Santosh, Vadakattu S; Mohammed, Saazida B; Ehtesham, Nasreen Z; Ibrahim, Ahamed

2012-11-14

Increasing prevalence of inflammatory bowel disease may be due to imbalance in the intake of n-6 and n-3 PUFA in the diet. This study investigates the impact of varying ratios of dietary linoleic acid (LA, 18 : 2n-6) to α-linolenic acid (ALA, 18 : 3n-3) on the inflammatory response in dextran sulphate sodium (DSS)-induced colitis. Weanling male Sprague-Dawley rats were divided into five groups: a non-colitic group with a LA:ALA ratio of 215 (CON-215), and colitic groups with LA:ALA ratios of 215 (DSS-215), 50 (DSS-50), 10 (DSS-10) and 2 (DSS-2). Blends of groundnut, palmolein and linseed oils were used to provide varying LA:ALA ratios. All the rats were fed the respective experimental isoenergetic diets containing 10 % fat for 90 d and DSS was administered during the last 11 d. Colonic inflammation was evaluated by clinical, biochemical and histological parameters. The results showed attenuation of colitis in the DSS-2 group as evidenced by significant reductions in disease activity index, mucosal myeloperoxidase activity (P < 0·05), alkaline phosphatase activity (P < 0·01) and increase in colon length (P < 0·01) compared to the groups fed with higher ratios (DSS-215). This was accompanied by significant reductions in mucosal proinflammatory cytokines TNF-α (P < 0·01) and IL-1β (P < 0·01) and improvement in the histological score. Further, ALA supplementation increased long-chain (LC) n-3 PUFA and decreased LC n-6 PUFA in colon structural lipids. These data suggest that substitution of one-third of LA with ALA (LA:ALA ratio 2) mitigates experimental colitis by down-regulating proinflammatory mediators.

Application of rat mast cell incubates as a possible short-time test for sensitizing occupational chemicals.

PubMed

Diel, F; Neidhart, B; Oprée, W

1981-01-01

The direct action of sensitizing occupational chemicals (formaldehyde, phenol, phenylhydrazine, p-aminophenol) on rat mast cells was investigated by determination of histamine using HPLC separation and fluorimetric detection. It turned out that dispensed mast cells from immunized and non-immunized Wistar-rats are more sensitive than small-cut lung tissue slices. Passive cutaneous anaphylaxis was negative after a fortnight sensitizing experiment with the here described occupational chemicals. Short-time tests with rat mast cells reflect anaphylactoid response and are suitable for the screening of sensitizing chemicals.

Alteration in contractile G-protein coupled receptor expression by moist snus and nicotine in rat cerebral arteries

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

Sandhu, Hardip, E-mail: sandhu.hardip@gmail.com; Xu Cangbao; Edvinsson, Lars

The cardiovascular risk for users of use of Swedish snus/American snuff (moist tobacco) has been debated for a long time. The present study was designed to examine the effects of water- or lipid-soluble (DMSO-soluble) snus and nicotine, the most important substance in tobacco, on the expression of vasocontractile G-protein coupled receptors (GPCR), such as endothelin ET{sub B}, serotonin 5-HT{sub 1B}, and thromboxane A{sub 2} TP receptors, in rat cerebral arteries. Studies show that these vasocontractile GPCR show alterations by lipid-soluble cigarette smoke particles via activation of mitogen-activated protein kinases (MAPK). However, the effects of moist tobacco on the expression ofmore » GPCR are less studied. Rat middle cerebral arteries were isolated and organ cultured in serum-free medium for 24 h in the presence of water-soluble snus (WSS), DMSO-soluble snus (DSS), or nicotine. The dose of snus and nicotine was kept at plasma level of snus users (25 ng nicotine/ml). A high dose (250 ng nicotine/ml) was also included due to the previous results showing alteration in the GPCR expression by nicotine at this concentration. Contractile responses to the ET{sub B} receptor agonist sarafotoxin 6c, 5-HT{sub 1B} receptor agonist 5-carboxamidotryptamine, and TP receptor agonist U46619 were investigated by a sensitive myograph. The expression of ET{sub B}, 5-HT{sub 1B}, and TP receptors was studied at mRNA and protein levels using quantitative real-time PCR and immunohistochemistry, respectively. Organ culture with WSS or DSS (25 ng nicotine/ml) lowered the 5-HT{sub 1B} receptor-mediated contraction. Furthermore, DSS shifted the TP receptor-mediated contraction curve left-wards with a stronger contraction. High dose of nicotine (250 ng nicotine/ml) increased the ET{sub B} receptor-mediated contraction. The combined 5-HT{sub 1B} and 5-HT{sub 2A} receptor-mediated contraction was increased, and both the 5-CT and TxA2 induced contractions were left-ward shifted by WSS

Enzyme-linked immunosorbent assay for S100A9 in the stool of rats with dextran sulfate sodium-induced colitis.

PubMed

Sekiya, Shunsuke; Murata, Makoto; Arai, Satoshi; Murayama, Hiroshi; Kawasaki, Atushi; Ashida, Noriyuki; Okada, Kohki; Ikemoto, Masaki

2016-12-01

Calprotectin, a heterodimer of S100A8 and S100A9, has been reported to be a useful biomarker in inflammatory bowel disease (IBD); however, the relationship between the fecal level of S100A9 and the extent of inflammation in IBD remains unclear. Our aim was to develop a new enzyme-linked immunosorbent assay (ELISA) for rat S100A9, and to investigate whether changes in fecal S100A9 levels reflect the inflammatory conditions in the intestinal tracts of rats with dextran sulfate sodium (DSS)-induced colitis. Anti-rat S100A9 monoclonal antibodies were raised in mice and used for the development of a novel ELISA for rat S100A9. The performance of our ELISA was assessed by dilution and recovery tests, and the detection range was 3.75-240ng/mL. The dilution test showed good linearity. The recovery of fecal S100A9 was 95.1% (mean), with a range of 86.1%-108.8%. Colitis was induced in rats by oral administration of 3% DSS/drinking water (DW) for 11days (D group), while DW alone was provided to rats of the control group (C group) during the same period. The extent of inflammation was evaluated with the disease activity index (DAI), and the concentration of fecal S100A9 was determined by ELISA. Both the DAI scores and the fecal S100A9 levels were significantly higher in the D group than in the C group. Microscopic observation revealed that S100A9 was dominantly produced in many immune cells of myeloid origin in rat rectal tissues. These results indicate that the novel ELISA may be applied to clinically evaluate IBD in rats with high sensitivity. In conclusion, our ELISA is useful in toxicological and pharmacological evaluations. Copyright © 2016 Elsevier B.V. All rights reserved.

Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.

PubMed

Eagle, Andrew L; Singh, Robby; Kohler, Robert J; Friedman, Amy L; Liebowitz, Chelsea P; Galloway, Matthew P; Enman, Nicole M; Jutkiewicz, Emily M; Perrine, Shane A

2015-05-01

Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague-Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0, 10 or 20 mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, as expected. However, compared to control rats on Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. Copyright © 2015. Published by Elsevier B.V.

A rapid enhancement of locomotor sensitization to amphetamine by estradiol in female rats.

PubMed

Zovkic, Iva B; McCormick, Cheryl M

2017-11-14

Estradiol moderates the effects of drugs of abuse in both humans and rodents. Estradiol's enhancement of behavioral effects resulting from high (>2.5mg/kg) doses of amphetamine is established in rats; there is less evidence for the role of estradiol in locomotor effects elicited by lower doses, which are less aversive, increase incentive motivation, involve different neural mechanisms than higher doses, and often more readily reveal group differences than do higher doses. Further, the extent to which estradiol is required for the induction versus the expression of sensitization is unknown. To establish a protocol, we replicated the effects of estradiol on locomotor sensitization to amphetamine reported in a previous study that involved a high locomotor-activating dose (1.5mg/kg) of amphetamine, but with a lower dose. Ovariectomized female rats received 5μg of estradiol benzoate (EB) or OIL 30min before each of 5 treatments of 1.0mg/kg amphetamine or saline; all received a 0.5mg/kg challenge dose three days later. Compared with results for OIL, EB enhanced the locomotor-activating effects of repeated 1.0mg/kg amphetamine across treatment days. In contrast, on challenge day, there was no difference between EB-saline and EB-amphetamine to the lower dose (i.e., no sensitization). Experiments 2 and 3 involved a shorter induction (2days) and a lengthier withdrawal (9days) before the challenge test for the expression of sensitization to better differentiate the induction phase from the expression phase. In Expt2, EB-, and not OIL-, treated rats showed sensitization to 0.5mg/kg amphetamine; neither group showed sensitization to 1.5mg/kg amphetamine (ceiling effect?). In Expt3, rats were treated with EB either in both the induction and expression phases, in one of the phases only, or in neither phase. There was an effect of hormone treatment on challenge day and not on induction day; rats given EB on Challenge day showed sensitization to 0.5mg/kg amphetamine; OIL rats did

Effect of confinement in small space flight size cages on insulin sensitivity of exercise-trained rats

NASA Technical Reports Server (NTRS)

Mondon, C. E.; Dolkas, C. B.; Reaven, G. M.

1983-01-01

The effect of confinement in small cages (simulating the size to be used in future space Shuttle missions) on insulin sensitivity was studied in rats having an increased insulin sensitivity due to exercise training prior to confinement. Oral glucose tolerance tests (OGTT) were given to both control and exercise-trained rats before and after placement in the small cages for 7 days. The insulin resistance was assessed by the product of the area of the insulin and glucose curves of the OGTT (IG index). Results show that the values obtained before confinement were one-half as high in exercise-trained rats as those in control rats, reflecting an increased sensitivity to insulin with exercise training. After 7 days confinement, the IG index was found to be not significantly different from initial values for both control and exercise-trained rats. These findings suggest that increased insulin sensitivity in exercise-trained rats persists 7 days after cessation of running activity. The data also indicate that exercise training, before flight, may be beneficial in minimizing the loss of insulin sensitivity expected with decreased use of gravity dependent muscles during exposure to hypogravity in space flight.

Replacement of salt by a novel potassium- and magnesium-enriched salt alternative improves the cardiovascular effects of ramipril.

PubMed Central

Mervaala, E. M.; Paakkari, I.; Laakso, J.; Nevala, R.; Teräväinen, T. M.; Fyhrquist, F.; Vapaatalo, H.; Karppanen, H.

1994-01-01

1. The influence of salt (sodium chloride; NaCl) (an additional 6% in the diet) and that of a novel sodium-reduced, potassium-, magnesium-, and L-lysine-enriched salt alternative on the cardiovascular effects of ramipril was studied in stroke-prone spontaneously hypertensive rats in a 6-week study. The intake of sodium chloride was adjusted to the same level by adding the salt alternative at a 1.75 times higher amount than regular salt. 2. Salt produced a marked rise in blood pressure and induced cardiac hypertrophy and significant mortality, while the salt alternative neither increased blood pressure nor caused any mortality and produced less cardiac hypertrophy than salt. 3. Ramipril treatment at a daily dose of 3 mg kg-1 normalized blood pressure and prevented the development of cardiac hypertrophy of rats on control diet. These effects of ramipril were blocked by the addition of salt but were only slightly attenuated by the addition of the salt alternative. The mortality in the salt group was prevented by ramipril. 4. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Salt, but not the salt alternative, increased vascular contractile responses to noradrenaline. Ramipril treatment improved the arterial relaxation responses to acetylcholine and to sodium nitroprusside. The vascular relaxation enhancing effect of ramipril was blocked by salt but only slightly attenuated by the salt alternative. 5. Ramipril treatment did not significantly increase plasma renin activity in the presence or in the absence of salt supplementation. The salt alternative did not cause hyperkalaemia, either alone or in combination with ramipril treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8032605

Disaster Metrics: Evaluation of de Boer's Disaster Severity Scale (DSS) Applied to Earthquakes.

PubMed

Bayram, Jamil D; Zuabi, Shawki; McCord, Caitlin M; Sherak, Raphael A G; Hsu, Edberdt B; Kelen, Gabor D

2015-02-01

Quantitative measurement of the medical severity following multiple-casualty events (MCEs) is an important goal in disaster medicine. In 1990, de Boer proposed a 13-point, 7-parameter scale called the Disaster Severity Scale (DSS). Parameters include cause, duration, radius, number of casualties, nature of injuries, rescue time, and effect on surrounding community. Hypothesis This study aimed to examine the reliability and dimensionality (number of salient themes) of de Boer's DSS scale through its application to 144 discrete earthquake events. A search for earthquake events was conducted via National Oceanic and Atmospheric Administration (NOAA) and US Geological Survey (USGS) databases. Two experts in the field of disaster medicine independently reviewed and assigned scores for parameters that had no data readily available (nature of injuries, rescue time, and effect on surrounding community), and differences were reconciled via consensus. Principle Component Analysis was performed using SPSS Statistics for Windows Version 22.0 (IBM Corp; Armonk, New York USA) to evaluate the reliability and dimensionality of the DSS. A total of 144 individual earthquakes from 2003 through 2013 were identified and scored. Of 13 points possible, the mean score was 6.04, the mode = 5, minimum = 4, maximum = 11, and standard deviation = 2.23. Three parameters in the DSS had zero variance (ie, the parameter received the same score in all 144 earthquakes). Because of the zero contribution to variance, these three parameters (cause, duration, and radius) were removed to run the statistical analysis. Cronbach's alpha score, a coefficient of internal consistency, for the remaining four parameters was found to be robust at 0.89. Principle Component Analysis showed uni-dimensional characteristics with only one component having an eigenvalue greater than one at 3.17. The 4-parameter DSS, however, suffered from restriction of scoring range on both parameter and scale levels. Jan de Boer

Importance of associative learning processes for one-trial behavioral sensitization of preweanling rats.

PubMed

McDougall, Sanders A; Pothier, Alexandria G; Der-Ghazarian, Taleen; Herbert, Matthew S; Kozanian, Olga O; Castellanos, Kevin A; Flores, Ana T

2011-10-01

During adulthood, associative learning is necessary for the expression of one-trial behavioral sensitization; however, it is uncertain whether the same associative processes are operative during the preweanling period. Two strategies were used to assess the importance of associative learning for one-trial behavioral sensitization of preweanling rats. In the initial experiments, we varied both the sequence and time interval between presentation of the conditioned stimulus (CS, novel environment) and unconditioned stimulus (US, cocaine). In the final experiment, we determined whether electroconvulsive shock-induced retrograde amnesia would disrupt one-trial behavioral sensitization. Results showed that robust-sensitized responding was apparent regardless of the sequence in which cocaine and the novel environment (the presumptive CS) were presented. Varying the time between CS and US presentation (0, 3, or 6 h) was also without effect. Results from experiment 3 showed that single or multiple electroconvulsive shock treatments did not alter the expression of the sensitized response. Therefore, these data indicated that one-trial behavioral sensitization of preweanling rats was exclusively mediated by nonassociative mechanisms and that associative processes did not modulate sensitized responding. These findings are in contrast to what is observed during adulthood, as adult rats exhibit one-trial behavioral sensitization only when associative processes are operative.

Changes in the Expression and Distribution of Claudins, Increased Epithelial Apoptosis, and a Mannan-Binding Lectin-Associated Immune Response Lead to Barrier Dysfunction in Dextran Sodium Sulfate-Induced Rat Colitis

PubMed Central

Yuan, Bosi; Zhou, Shuping; Lu, Youke; Liu, Jiong; Jin, Xinxin; Wan, Haijun; Wang, Fangyu

2015-01-01

Background/Aims This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. Methods Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. Results The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%±1.2% in controls and was significantly increased to 7.2%±1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. Conclusions There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability. PMID:25717051

Changes in the Expression and Distribution of Claudins, Increased Epithelial Apoptosis, and a Mannan-Binding Lectin-Associated Immune Response Lead to Barrier Dysfunction in Dextran Sodium Sulfate-Induced Rat Colitis.

PubMed

Yuan, Bosi; Zhou, Shuping; Lu, Youke; Liu, Jiong; Jin, Xinxin; Wan, Haijun; Wang, Fangyu

2015-11-23

This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%±1.2% in controls and was significantly increased to 7.2%±1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability.

The sensitivity of male rat reproductive organs to monosodium glutamate.

PubMed

Iamsaard, Sitthichai; Sukhorum, Wannisa; Samrid, Rarinthorn; Yimdee, Jindaporn; Kanla, Pipatphong; Chaisiwamongkol, Kowit; Hipkaeo, Wiphawi; Fongmoon, Duriya; Kondo, Hisatake

2014-01-01

This study aimed to investigate the sensitivity of the testis, epididymis, seminal vesicle, and sperm acrosome reaction (AR) to monosodium L- glutamate (MSG) in rats. Rats were divided into four groups and fed with non-acidic MSG at 0.25, 3 or 6 g/kg body weight for 30 days or without MSG. The morphological changes in the reproductive organs were studied. The plasma testosterone level, epididymal sperm concentration, and sperm AR status were assayed. Compared to the control, no significant changes were discerned in the morphology and weight of the testes, or the histological structures of epididymis, vas deferens and seminal vesicle. In contrast, significant decreases were detected in the weight of the epididymis, testosterone levels, and sperm concentration of rats treated with 6 g/kg body weight of MSG. The weight loss was evident in the seminal vesicle in MSG-administered rats. Moreover, rats treated with MSG 3 and 6 g/kg exhibited partial testicular damage, characterized by sloughing of spermatogenic cells into the seminiferous tubular lumen, and their plasma testosterone levels were significantly decreased. In the 6 g/kg MSG group, the sperm concentration was significantly decreased compared with the control or two lower dose MSG groups. In AR assays, there was no statistically significant difference between MSG-rats and normal rats. Testicular morphological changes, testosterone level, and sperm concentration were sensitive to high doses of MSG while the rate of AR was not affected. Therefore, the consumption of high dose MSG must be avoided because it may cause partial infertility in male. Copyright © 2014 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Bronchoconstriction induced by increasing airway temperature in ovalbumin-sensitized rats: role of tachykinins.

PubMed

Hsu, Chun-Chun; Lin, Ruei-Lung; Lin, You Shuei; Lee, Lu-Yuan

2013-09-01

This study was carried out to determine the effect of allergic inflammation on the airway response to increasing airway temperature. Our results showed the following: 1) In Brown-Norway rats actively sensitized by ovalbumin (Ova), isocapnic hyperventilation with humidified warm air (HWA) for 2 min raised tracheal temperature (Ttr) from 33.4 ± 0.6°C to 40.6 ± 0.1°C, which induced an immediate and sustained (>10 min) increase in total pulmonary resistance (Rl) from 0.128 ± 0.004 to 0.212 ± 0.013 cmH2O·ml(-1)·s (n = 6, P < 0.01). In sharp contrast, the HWA challenge caused the same increase in Ttr but did not generate any increase in Rl in control rats. 2) The increase in Rl in sensitized rats was reproducible when the same HWA challenge was repeated 60-90 min later. 3) This bronchoconstrictive effect was temperature dependent: a slightly smaller increase in peak Ttr (39.6 ± 0.2°C) generated a significant but smaller increase in Rl in sensitized rats. 4) The HWA-induced bronchoconstriction was not generated by the humidity delivered by the HWA challenge alone, because the same water content delivered by saline aerosol at room temperature had no effect. 5) The HWA-evoked increase in Rl in sensitized rats was not blocked by atropine but was completely prevented by pretreatment either with a combination of neurokinin (NK)-1 and NK-2 antagonists or with formoterol, a β2 agonist, before the HWA challenge. This study showed that increasing airway temperature evoked a pronounced and reversible increase in airway resistance in sensitized rats and that tachykinins released from the vagal bronchopulmonary C-fiber endings were primarily responsible.

Application of a participative process for DSS development in soil remediation

NASA Astrophysics Data System (ADS)

José Blanco-Velázquez, Francisco; Muñoz-Vallés, Sara; Anaya-Romero, María

2017-04-01

A wide range of current legislation concerning environmental protection and public health at the national and international level include mandatory actions related to site characterization and the implementation of effective soil remediation measures. The efficiency, in terms of reliability and costs, of this kind of assessment, involves the development and linkage of integrated-harmonized databases, simulating models and specialization tools. So far, no data/knowledge engineering technologies in the academy or market provides the possibility for simulating soil remediation processes for hypothetic spatio-temporal scenarios in a harmonized manner across Europe. In this context, under the framework of RECARE (Preventing and Remediating degradation of Soils in Europe through Land Care) project, we are designing a Decision Support System (DSS) comprising a large database of knowledge including soil, climatic and socio-economic attributes, focused on soil remediation techniques that allows the user to automatically perform a more accurate quantifying of soil pollution, spatial identification of vulnerable zones and formulation of action programs to deal with the particular problem under scenarios of climate and land-use changes. The pilot study area is the Guadiamar valley (SW Spain) where the main threat is soil contamination, after a mine spill occurred on April 1998. About four hm3 of acid waters and two hm3 of mud, rich in heavy metals, were released into the Agrio and Guadiamar rivers affecting more than 4,600 ha of agricultural and pasture land. Consequently, the area was subjected to a large-scale phyto-management project, including the removal of sludge and topsoil, the addition of amendments, and plantation of native shrubs and trees. The objective of this research is to test the feasibility of the DSS concept as well as the likelihood to establish a solid high-potential innovation tool, aligned with the scientific and market strategy and within a European

Extraction, scrub, and strip test results for the salt waste processing facility caustic side solvent extraction solvent example

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

Peters, T. B.

An Extraction, Scrub, and Strip (ESS) test was performed on a sample of Salt Waste Processing Facility (SWPF) Caustic-Side Solvent Extraction (CSSX) solvent and salt simulant to determine cesium distribution ratios (D(Cs)), and cesium concentration in the strip effluent (SE) and decontaminated salt solution (DSS) streams; this data will be used by Parsons to help determine if the solvent is qualified for use at the SWPF. The ESS test showed acceptable performance of the solvent for extraction, scrub, and strip operations. The extraction D(Cs) measured 12.9, exceeding the required value of 8. This value is consistent with results from previousmore » ESS tests using similar solvent formulations. Similarly, scrub and strip cesium distribution ratios fell within acceptable ranges.« less

Sensitization of TRPV1 by protein kinase C in rats with mono-iodoacetate-induced joint pain.

PubMed

Koda, K; Hyakkoku, K; Ogawa, K; Takasu, K; Imai, S; Sakurai, Y; Fujita, M; Ono, H; Yamamoto, M; Fukuda, I; Yamane, S; Morita, A; Asaki, T; Kanemasa, T; Sakaguchi, G; Morioka, Y

2016-07-01

To assess the functional changes of Transient receptor potential vanilloid 1 (TRPV1) receptor and to clarify its mechanism in a rat mono-iodoacetate (MIA)-induced joint pain model (MIA rats), which has joint degeneration with cartilage loss similar to osteoarthritis. Sensitization of TRPV1 in MIA rats was assessed by transient spontaneous pain behavior induced by capsaicin injection in knee joints and electrophysiological changes of dorsal root ganglion (DRG) neurons innervating knee joints in response to capsaicin. Mechanisms of TRPV1 sensitization were analyzed by a newly developed sandwich enzyme-linked immunosorbent assay that detects phosphorylated TRPV1, followed by functional and expression analyses of protein kinase C (PKC) in vivo and in vitro, which involves TRPV1 phosphorylation. Pain-related behavior induced by intra-articular injection of capsaicin was significantly increased in MIA rats compared with sham rats. In addition, capsaicin sensitivity, evaluated by capsaicin-induced inward currents, was significantly increased in DRG neurons of MIA rats. Protein levels of TRPV1 remained unchanged, but phosphorylated TRPV1 at Ser800 increased in DRG neurons of MIA rats. Phosphorylated-PKCɛ (p-PKCɛ) increased and co-localized with TRPV1 in DRG neurons of MIA rats. Capsaicin-induced pain-related behavior in MIA rats was inhibited by intra-articular pretreatment of the PKC inhibitor bisindolylmaleimide I. In addition, intra-articular injection of the PKC activator phorbol 12-myristate 13-acetate increased capsaicin-induced pain-related behavior in normal rats. TRPV1 was sensitized at the knee joint and at DRG neurons of MIA rats through PKC activation. Thus, TRPV1 sensitization might be involved in chronic pain caused by osteoarthritis. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

The efficiency calibration of the DSS-24 34-meter beam-waveguide antenna

NASA Technical Reports Server (NTRS)

Alvarez, L. S.; Britcliffe, M. J.; Franco, M. M.; Stewart, S. R.; Jackson, H. J.

1995-01-01

Microwave performance testing of the new Deep Space Station (DSS)-24 34-m-diameter antenna was carried out during the summer of 1994. Efficiency measurements were made at the 8.45 GHz (X-band) and 32-GHz (ka-band) frequencies both at the antenna Cassegrian (f1) and beam-waveguide (f3) focal points. In addition, the antenna f3 efficiencies were measured on the DSS-24 operational 2.295-GHz (S-band) and 8.45-Ghz feeds. This article presents the efficiency determinations as a function of elevation angle along with a corresponding error analysis of the measurements. Peak measured gains and efficiencies are tabulated for all frequencies.

Amnesia induced by morphine in spatial memory retrieval inhibited in morphine-sensitized rats.

PubMed

Farahmandfar, Maryam; Naghdi, Nasser; Karimian, Seyed Morteza; Kadivar, Mehdi; Zarrindast, Mohammad-Reza

2012-05-15

The present study investigated the effect of morphine sensitization on the impairment of spatial memory retrieval induced by acute morphine in adult male rats. Spatial memory was assessed by 2-day Morris water maze task which included training and test day. On the training day, rats were trained by a single training session of 8 trials. On the test day, a probe trial consisting of 60s free swim period without a platform and the visible test were administered. Morphine sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days without drug treatment before training. The results indicated that acute administration of morphine (7.5mg/kg, s.c.) before testing impaired spatial memory on the test day. Pre-test morphine-induced amnesia decreased in morphine-sensitized (15 and 20mg/kg, s.c.) rats. Improvement in spatial memory retrieval in morphine-sensitized rats was inhibited by once daily administration of naloxone (1 and 2mg/kg, s.c.) 30 min prior to the injection of morphine for three days. The results suggest that morphine sensitization reverses the impairment of spatial memory retrieval induced by acute morphine and it is implied that mu-opioid receptors may play an important role in this effect. Copyright © 2012 Elsevier B.V. All rights reserved.

The effects of amphetamine sensitization on conditioned inhibition during a Pavlovian-instrumental transfer task in rats.

PubMed

Shiflett, Michael W; Riccie, Meaghan; DiMatteo, RoseMarie

2013-11-01

Psychostimulant sensitization heightens behavioral and motivational responses to reward-associated stimuli; however, its effects on stimuli associated with reward absence are less understood. We examined whether amphetamine sensitization alters performance during Pavlovian-instrumental transfer (PIT) to conditioned excitors and inhibitors. We further sought to characterize the effects of amphetamine sensitization on learning versus performance by exposing rats to amphetamine prior to Pavlovian training or between training and test. Adult male Long-Evans rats were given conditioned inhibition (A+/AX-) and Pavlovian (B+) training, followed by variable-interval instrumental conditioning. Rats were sensitized to D-amphetamine (2 mg/kg daily injections for 7 days) or served as non-exposed controls. Rats were given a PIT test, in which they were presented with stimulus B alone or in compound with the conditioned inhibitor (BX). During the PIT test, control rats significantly reduced instrumental responding on BX trials (to approximately 50 % of responding to B). Amphetamine sensitization prior to Pavlovian conditioning increased lever pressing on BX trials and reduced lever pressing on B trials compared to controls. Amphetamine sensitization between training and test increased lever pressing on B and BX trials compared to controls. No effects of sensitization were observed on conditioned food cup approach. Amphetamine sensitization increases instrumental responding during PIT to a conditioned inhibitor by enhancing the excitation of conditioned stimuli and reducing the inhibition of conditioned inhibitors.

Azilsartan Improves Salt Sensitivity by Modulating the Proximal Tubular Na+-H+ Exchanger-3 in Mice.

PubMed

Hatanaka, Masaki; Kaimori, Jun-Ya; Yamamoto, Satoko; Matsui, Isao; Hamano, Takayuki; Takabatake, Yoshitsugu; Ecelbarger, Carolyn M; Takahara, Shiro; Isaka, Yoshitaka; Rakugi, Hiromi

2016-01-01

A potent angiotensin II type-1 receptor blocker, azilsartan, has been reported to reduce blood pressure more effectively than candesartan. Interestingly, azilsartan can also restore the circadian rhythm of blood pressure. We hypothesized that azilsartan could also improve salt sensitivity; thus, we examined the effect of azilsartan on sodium handling in renal tubules. Subtotal nephrectomized C57BL/6 mice received azilsartan (1.0 mg/kg/day), candesartan (0.3 mg/kg/day), or vehicle via the oral route in conjunction with a normal- (0.3%) or high-salt (8.0%) diet. Two weeks later, the azilsartan group showed significantly lower blood pressure during the light period than the candesartan and vehicle groups (azilsartan: 103.1 ± 1.0; candesartan: 111.7 ± 2.7; vehicle: 125.5 ± 2.5 mmHg; P < 0.05; azilsartan or candesartan vs. vehicle). The azilsartan group also showed higher urinary fractional excretion of sodium during the dark period than the candesartan and vehicle groups (azilsartan: 21.37 ± 3.69%; candesartan: 14.17 ± 1.42%; vehicle: 13.85 ± 5.30%; P < 0.05 azilsartan vs. candesartan or vehicle). A pressure-natriuresis curve demonstrated that azilsartan treatment restored salt sensitivity. Immunofluorescence and western blotting showed lower levels of Na+-H+ exchanger-3 (NHE3) protein (the major sodium transporter in renal proximal tubules) in the azilsartan group, but not in the candesartan or vehicle groups. However, azilsartan did not affect NHE3 transcription levels. Interestingly, we did not observe increased expression of downstream sodium transporters, which would have compensated for the increased flow of sodium and water due to non-absorption by NHE3. We also confirmed the mechanism stated above using cultured opossum kidney proximal tubular cells. Results revealed that a proteasomal inhibitor (but not a lysosomal inhibitor) blocked the azilsartan-induced decrease in NHE3 protein expression, suggesting that azilsartan increases NHE3 ubiquitination. In

Azilsartan Improves Salt Sensitivity by Modulating the Proximal Tubular Na+-H+ Exchanger-3 in Mice

PubMed Central

Hatanaka, Masaki; Kaimori, Jun-Ya; Yamamoto, Satoko; Matsui, Isao; Hamano, Takayuki; Takabatake, Yoshitsugu; Ecelbarger, Carolyn M.; Takahara, Shiro; Isaka, Yoshitaka; Rakugi, Hiromi

2016-01-01

A potent angiotensin II type-1 receptor blocker, azilsartan, has been reported to reduce blood pressure more effectively than candesartan. Interestingly, azilsartan can also restore the circadian rhythm of blood pressure. We hypothesized that azilsartan could also improve salt sensitivity; thus, we examined the effect of azilsartan on sodium handling in renal tubules. Subtotal nephrectomized C57BL/6 mice received azilsartan (1.0 mg/kg/day), candesartan (0.3 mg/kg/day), or vehicle via the oral route in conjunction with a normal- (0.3%) or high-salt (8.0%) diet. Two weeks later, the azilsartan group showed significantly lower blood pressure during the light period than the candesartan and vehicle groups (azilsartan: 103.1 ± 1.0; candesartan: 111.7 ± 2.7; vehicle: 125.5 ± 2.5 mmHg; P < 0.05; azilsartan or candesartan vs. vehicle). The azilsartan group also showed higher urinary fractional excretion of sodium during the dark period than the candesartan and vehicle groups (azilsartan: 21.37 ± 3.69%; candesartan: 14.17 ± 1.42%; vehicle: 13.85 ± 5.30%; P < 0.05 azilsartan vs. candesartan or vehicle). A pressure—natriuresis curve demonstrated that azilsartan treatment restored salt sensitivity. Immunofluorescence and western blotting showed lower levels of Na+-H+ exchanger-3 (NHE3) protein (the major sodium transporter in renal proximal tubules) in the azilsartan group, but not in the candesartan or vehicle groups. However, azilsartan did not affect NHE3 transcription levels. Interestingly, we did not observe increased expression of downstream sodium transporters, which would have compensated for the increased flow of sodium and water due to non-absorption by NHE3. We also confirmed the mechanism stated above using cultured opossum kidney proximal tubular cells. Results revealed that a proteasomal inhibitor (but not a lysosomal inhibitor) blocked the azilsartan-induced decrease in NHE3 protein expression, suggesting that azilsartan increases NHE3 ubiquitination. In

Direct renal effects of a fructose-enriched diet: interaction with high salt intake

PubMed Central

Ares, Gustavo R.

2015-01-01

Consumption of fructose has increased during the last 50 years. Excessive fructose consumption has a detrimental effect on mammalian health but the mechanisms remain unclear. In humans, a direct relationship exists between dietary intake of added sugars and increased risk for cardiovascular disease mortality (52). While the causes for this are unclear, we recently showed that fructose provided in the drinking water induces a salt-dependent increase in blood pressure in Sprague-Dawley rats in a matter of days (6). However, little is known about the effects of fructose in renal salt handling and whether combined intake of high fructose and salt can lead to salt-sensitive hypertension before the development of metabolic abnormalities. The long-term (more than 4 wk) adverse effects of fructose intake on renal function are not just due to fructose but are also secondary to alterations in metabolism which may have an impact on renal function. This minireview focuses on the acute effect of fructose intake and its effect on salt regulation, as they affect blood pressure. PMID:26447210

Fos Expression in Rat Brain During Depletion-Induced Thirst and Salt Appetite

NASA Technical Reports Server (NTRS)

Thunhorst, R. L.; Xu, Z.; Cicha, M. Z.; Zardetto-Smith, A. M.; Johnson, A. K.

1998-01-01

The expression of Fos protein (Fos immunoreactivity, Fos-ir) was mapped in the brain of rats subjected to an angiotensin-dependent model of thirst and salt appetite. The physiological state associated with water and sodium ingestion was produced by the concurrent subcutaneous administration of the diuretic furosemide (10 mg/kg) and a low dose of the angiotensin-converting enzyme (ACE) inhibitor captopril (5 mg/kg; Furo/Cap treatment). The animals were killed 2 h posttreatment, and the brains were processed for Fos-ir to assess neural activation. Furo/Cap treatment significantly increased Fos-ir density above baseline levels both in structures of the lamina terminalis and hypothalamus known to mediate the actions of ANG 2 and in hindbrain regions associated with blood volume and pressure regulation. Furo/Cap treatment also typically increased Fos-ir density in these structures above levels observed after administration of furosemide or captopril separately. Fos-ir was reduced to a greater extent in forebrain than in hindbrain areas by a dose of captopril (100 mg/kg sc) known to block the actions of ACE in the brain. The present work provides further evidence that areas of lamina terminalis subserve angiotensin-dependent thirst and salt appetite.

Extraction-Scrub-Strip test results from the interim Salt Disposition Program Macrobatch 9 Tank 21H qualification samples

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

Peters, T.

2016-02-23

Savannah River National Laboratory (SRNL) analyzed samples from Tank 21H in support of qualification of Macrobatch (Salt Batch) 9 for the Interim Salt Disposition Program (ISDP). The Salt Batch 9 characterization results were previously reported. An Extraction-Scrub-Strip (ESS) test was performed to determine cesium distribution ratios (D (Cs)) and cesium concentration in the strip effluent and decontaminated salt solution (DSS) streams; this data will be used by Tank Farm Engineering to project a cesium decontamination factor (DF). This test used actual Tank 21H material, and a blend solvent prepared by SRNL that mimics the solvent composition currently being used atmore » the Modular Caustic-Side Solvent Extraction Unit (MCU). The ESS test showed acceptable performance with an extraction D (Cs) value of 52.4. This value is consistent with results from previous salt batch ESS tests using similar solvent formulations. This compares well against the predicted value of 56.5 from a recently created D (Cs) model« less

Extraction, -scrub, -strip test results from the interim salt disposition program macrobatch 10 tank 21H qualification samples

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

Peters, T. B.

Savannah River National Laboratory (SRNL) analyzed samples from Tank 21H in support of qualification of Macrobatch (Salt Batch) 10 for the Interim Salt Disposition Program (ISDP). The Salt Batch 10 characterization results were previously reported.ii,iii An Extraction, -Scrub, -Strip (ESS) test was performed to determine cesium distribution ratios (D(Cs)) and cesium concentration in the strip effluent (SE) and decontaminated salt solution (DSS) streams; this data will be used by Tank Farm Engineering to project a cesium decontamination factor (DF). This test used actual Tank 21H material, and a sample of the NGS Blend solvent currently being used at the Modularmore » Caustic-Side Solvent Extraction Unit (MCU). The ESS test showed acceptable performance with an extraction D(Cs) value of 110. This value is consistent with results from previous salt batch ESS tests using similar solvent formulations. This is better than the predicted value of 39.8 from a recently created D(Cs) model.« less

Maternal fructose and/or salt intake and reproductive outcome in the rat: effects on growth, fertility, sex ratio, and birth order.

PubMed

Gray, Clint; Long, Sophie; Green, Charlotte; Gardiner, Sheila M; Craigon, Jim; Gardner, David S

2013-09-01

Maternal diet can significantly skew the secondary sex ratio away from the expected value of 0.5 (proportion males), but the details of how diet may do this are unclear. Here, we altered dietary levels of salt (4% salt in the feed) and/or fructose (10% in the drinking water) of pregnant rats to model potential effects that consumption of a "Western diet" might have on maternofetal growth, development, and sex ratio. We demonstrate that excess fructose consumption before and during pregnancy lead to a marked skew in the secondary sex ratio (proportion of males, 0.60; P < 0.006). The effect was not mediated by selective developmental arrest of female embryos or influenced by fetal position in the uterine horn or sex-specific effects on sperm motility, suggesting a direct effect of glycolyzable monosaccharide on the maternal ovary and/or ovulated oocyte. Furthermore, combined excess maternal consumption of salt and fructose-sweetened beverage significantly reduced fertility, reflected as a 50% reduction in preimplantation and term litter size. In addition, we also noted birth order effects in the rat, with sequential implantation sites tending to be occupied by the same sex.

Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats

PubMed Central

Eagle, Andrew L.; Singh, Robby; Kohler, Robert J.; Friedman, Amy L.; Liebowitz, Chelsea P.; Galloway, Matthew P.; Enman, Nicole M.; Jutkiewicz, Emily M.; Perrine, Shane A.

2017-01-01

Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague–Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0,10 or 20mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, asexpected. However, compared to control ratson Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. PMID:25712697

Pyridinium molten salts as co-adsorbents in dye-sensitized solar cells

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

Chang, Jui-Cheng; Sun, I-Wen; Yang, Cheng-Hsien

2011-01-15

The influence of using pyridinium molten salts as co-adsorbents to modify the monolayer of a TiO{sub 2} semiconductor on the performance of a dye-sensitized solar cell is studied. The current-voltage characteristics are measured under AM 1.5 (100 mW cm{sup -2}). The pyridinium molten salts significantly enhance the open-circuit photovoltage (V{sub oc}), the short circuit photocurrent density (J{sub sc}) as well as the solar energy conversion efficiency ({eta}). 1-Ethyl-3-carboxypyridinium iodide ([ECP][I]) is applied successfully to prepare an insulating molecular layer with N719, and achieve high energy conversion efficiency as high as 4.49% at 100 mW cm{sup -2} and AM 1.5. Themore » resulting efficiency is 20% higher than that of a non-additive device. This enhancement of conversion efficiency is attributed to the negative shift of the conduction band (CB) edge and the abundant concentration of I{sup -} on the surface of the electrode when using [ECP][I] as the co-adsorbent. (author)« less

Comparative 2D-DIGE analysis of salinity responsive microsomal proteins from leaves of salt-sensitive Arabidopsis thaliana and salt-tolerant Thellungiella salsuginea.

PubMed

Vera-Estrella, Rosario; Barkla, Bronwyn J; Pantoja, Omar

2014-12-05

Halophytes have evolved unique molecular strategies to overcome high soil salinity but we still know very little about the main mechanisms that these plants use to complete their lifecycle under salinity stress. One useful approach to further our understanding in this area is to directly compare the response to salinity of two closely related species which show diverse levels of salt tolerance. Here we present a comparative proteomic study using DIGE of leaf microsomal proteins to identify salt-responsive membrane associated proteins in Arabidopsis thaliana (a glycophyte) and Thellungiella salsuginea (a halophyte). While a small number of distinct protein abundance changes were observed upon salt stress in both species, the most notable differences were observed between species and specifically, in untreated plants with a total of 36 proteins displaying significant abundance changes. Gene ontology (GO) term enrichment analysis showed that the majority of these proteins were distributed into two functional categories; transport (31%) and carbohydrate metabolism (17%). Results identify several novel salt responsive proteins in this system and support the theory that T. salsuginea shows a high degree of salt-tolerance because molecular mechanisms are primed to deal with the stress. This intrinsic ability to anticipate salinity stress distinguishes it from the glycophyte A. thaliana. There is significant interest in understanding the molecular mechanisms that plants use to tolerate salinity as soil salinization is becoming an increasing concern for agriculture with high soil Na(+) levels leading to reduced yields and economic loss. Much of our knowledge on the molecular mechanisms employed by plants to combat salinity stress has come from work on salt-sensitive plants, but studies on naturally occurring highly salt-resistant plants, halophytes, and direct comparisons between closely related glycophytes and halophytes, could help to further our understanding of salinity

Putrescine differently influences the effect of salt stress on polyamine metabolism and ethylene synthesis in rice cultivars differing in salt resistance

PubMed Central

Quinet, Muriel; Lefèvre, Isabelle; Lambillotte, Béatrice; Dupont-Gillain, Christine C.; Lutts, Stanley

2010-01-01

Effects of salt stress on polyamine metabolism and ethylene production were examined in two rice (Oryza sativa L.) cultivars [I Kong Pao (IKP), salt sensitive; and Pokkali, salt resistant] grown for 5 d and 12 d in nutrient solution in the presence or absence of putrescine (1 mM) and 0, 50, and 100 mM NaCl. The salt-sensitive (IKP) and salt-resistant (Pokkali) cultivars differ not only in their mean levels of putrescine, but also in the physiological functions assumed by this molecule in stressed tissues. Salt stress increased the proportion of conjugated putrescine in salt-resistant Pokkali and decreased it in the salt-sensitive IKP, suggesting a possible protective function in response to NaCl. Activities of the enzymes ornithine decarboxylase (ODC; EC 4.1.1.17) and arginine decarboxylase (ADC; EC 4.1.1.19) involved in putrescine synthesis were higher in salt-resistant Pokkali than in salt-sensitive IKP. Both enzymes were involved in the response to salt stress. Salt stress also increased diamine oxidase (DAO; 1.4.3.6) and polyamine oxidase (PAO EC 1.5.3.11) activities in the roots of salt-resistant Pokkali and in the shoots of salt-sensitive IKP. Gene expression followed by reverse transcription-PCR suggested that putrescine could have a post-translational impact on genes coding for ADC (ADCa) and ODC (ODCa and ODCb) but could induce a transcriptional activation of genes coding for PAO (PAOb) mainly in the shoot of salt-stressed plants. The salt-resistant cultivar Pokkali produced higher amounts of ethylene than the salt-sensitive cultivar IKP, and exogenous putrescine increased ethylene synthesis in both cultivars, suggesting no direct antagonism between polyamine and ethylene pathways in rice. PMID:20472577

[Effects-of combined calories restriction and polyunsaturated fatty acids on colitis in rats].

PubMed

Qian, Yan; Zhang, Ying; Liu, Hui; Wang, Lei; Li, Xiuhua; Qiu, Fubin

2014-09-01

To explore the effect of n-6 and n-3 polyunsaturated fatty acids combined with calorie restriction( CR) in DSS induced ulcerative colitis rats. Forty female rats were randomly divided into five groups, control group, model group, CR group, 5:1 PUFA ad libitum group, 5: 1 PUFA CR group. CR groups provided with a limited daily food allotment of 60% of that eaten by the ad libitum animals for 14 weeks. Ulcerative colitis model in rats were given 5. 0% dextran sulfate sodium in their drinking water for 7 days. 5:1 PUFA CR group significantly decreased body weight, disease activity index, macroscopic and histological score compared to model group. In addition, administration of 5: 1 PUFA CR effectively inhibited MPO activity. The levels of TNF-α and IL-6 in the serum with colitis were decreased by 5: 1 PUFA CR (P <0. 05). These results suggest that combination of calories restriction and n-6/n-3 =5:1 PUFA may be more beneficial in attenuating the progression of DSS induced ulcerative colitis.

Neurological and cellular regulation of visceral hypersensitivity induced by chronic stress and colonic inflammation in rats.

PubMed

Chen, J; Winston, J H; Sarna, S K

2013-09-17

The role of inflammation in inducing visceral hypersensitivity (VHS) in ulcerative colitis patients remains unknown. We tested the hypothesis that acute ulcerative colitis-like inflammation does not induce VHS. However, it sets up molecular conditions such that chronic stress following inflammation exaggerates single-unit afferent discharges to colorectal distension. We used dextran sodium sulfate (DSS) to induce ulcerative colitis-like inflammation and a 9-day heterotypic chronic stress protocol in rats. DSS upregulated Nav1.8 mRNA in colon-responsive dorsal root ganglion (DRG) neurons, TRPV1 in colonic muscularis externae (ME) and BDNF in spinal cord without affecting the spike frequency in spinal afferents or VMR to CRD. By contrast, chronic stress did not induce inflammation but it downregulated Kv1.1 and Kv1.4 mRNA in DRG neurons, and upregulated TRPA1 and nerve growth factor in ME, which mediated the increase of spike frequency and VMR to CRD. Chronic stress following inflammation exacerbated spike frequency in spinal afferent neurons. TRPA1 antagonist suppressed the sensitization of afferent neurons. DSS-inflammation did not affect the composition or excitation thresholds of low-threshold and high-threshold fibers. Chronic stress following inflammation increased the percent composition of high-threshold fibers and lowered the excitation threshold of both types of fibers. We conclude that not all types of inflammation induce VHS, whereas chronic stress induces VHS in the absence of inflammation. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

The effects of amphetamine sensitization on conditioned inhibition during a Pavlovian-instrumental transfer task in rats

PubMed Central

Shiflett, Michael W.; Riccie, Meaghan; DiMatteo, RoseMarie

2013-01-01

Rationale Psychostimulant sensitization heightens behavioral and motivational responses to reward-associated stimuli; however, its effects on stimuli associated with reward absence are less understood. Objectives We examined whether amphetamine sensitization alters performance during Pavlovian-instrumental transfer (PIT) to conditioned excitors and inhibitors. We further sought to characterize the effects of amphetamine sensitization on learning versus performance by exposing rats to amphetamine prior to Pavlovian training or between training and test. Methods Adult male Long Evans rats were given conditioned inhibition (A+/AX−) and Pavlovian (B+) training, followed by variable-interval instrumental conditioning. Rats were sensitized to d-amphetamine (2 mg/kg daily injections for seven days), or served as non-exposed controls. Rats were given a PIT test, in which they were presented with stimulus B alone or in compound with the conditioned inhibitor (BX). Results During the PIT test, control rats significantly reduced instrumental responding on BX trials (to approximately 50% of responding to B). Amphetamine sensitization prior to Pavlovian conditioning increased lever-pressing on BX trials and reduced lever-pressing on B trials compared to controls. Amphetamine sensitization between training and test increased lever-pressing on B and BX trials compared to controls. No effects of sensitization were observed on conditioned food-cup approach. Conclusions Amphetamine sensitization increases instrumental responding during PIT to a conditioned inhibitor, by enhancing excitation of conditioned stimuli and reducing inhibition of conditioned inhibitors. PMID:23715640

Salt stress differentially affects growth-mediating β-expansins in resistant and sensitive maize (Zea mays L.).

PubMed

Geilfus, Christoph-Martin; Zörb, Christian; Mühling, Karl H

2010-12-01

Salinity mainly reduces shoot growth by the inhibition of cell division and elongation. Expansins loosen plant cell walls. Moreover, the expression of some isoforms is clearly correlated with growth. Effects of salinity on β-expansin transcripts protein abundance were recently reported for different crop species. This study provides a broad analysis of the impact of an 8-day 100mM NaCl stress treatment on the mRNA expression of different maize (Zea mays L.) β-Expansin isoforms using real-time quantitative RT-PCR. The composite β-expansin protein expression was analyzed by western blotting using an anti-peptide antibody raised against a conserved 15-amino-acid region shared by vegetatively expressed β-expansin isoforms. For the first time, changes in β-expansin transcript and protein abundance have been analyzed together with the salinity-induced inhibition of shoot growth. A salt-resistant and a salt-sensitive cultivar were compared in order to elucidate physiological changes. Genotypic differences in the relative concentration of six β-expansin transcripts together with differences in the abundance β-expansin protein are shown in response NaCl stress. In salt-sensitive Lector, reduced β-expansin protein expression was found to correlate positively with reduced shoot growth under stress. A down-regulation of ZmExpB2, ZmExpB6, and ZmExpB8 transcripts possibly contribute to this decrease in protein abundance. In contrast, the maintenance of shoot growth in salt-resistant SR03 might be related to an unaffected abundance of growth-mediating β-expansin proteins in the shoot. Our data suggest that the up-regulation of ZmExpB2, ZmExpB6, and ZmExpB8 may sustain the stable expression of β-expansin protein under conditions of salt stress. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Aluminium sensitized spectrofluorimetric determination of fluoroquinolones in milk samples coupled with salting-out assisted liquid-liquid ultrasonic extraction

NASA Astrophysics Data System (ADS)

Xia, Qinghai; Yang, Yaling; Liu, Mousheng

2012-10-01

An aluminium sensitized spectrofluorimetric method coupled with salting-out assisted liquid-liquid ultrasonic extraction for the determination of four widely used fluoroquinolones (FQs) namely norfloxacin (NOR), ofloxacin (OFL), ciprofloxacin (CIP) and gatifloxacin (GAT) in bovine raw milk was described. The analytical procedure involves the fluorescence sensitization of aluminium (Al3+) by complexation with FQs, salting-out assisted liquid-liquid ultrasonic extraction (SALLUE), followed by spectrofluorometry. The influence of several parameters on the extraction (the salt species, the amount of salt, pH, temperature and phase volume ratio) was investigated. Under optimized experimental conditions, the detection limits of the method in milk varied from 0.009 μg/mL for NOR to 0.016 μg/mL for GAT (signal-to-noise ratio (S/N) = 3). The relative standard deviations (RSD) values were found to be relatively low (0.54-2.48% for four compounds). The calibration graph was linear from 0.015 to 2.25 μg/mL with coefficient of determinations not less than 0.9974. The methodology developed was applied to the determination of FQs in bovine raw milk samples. The main advantage of this method is simple, accurate and green. The method showed promising applications for analyzing polar analytes especially polar drugs in various sample matrices.

Effect of kefir and low-dose aspirin on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet.

PubMed

Kanbak, Güngör; Uzuner, Kubilay; Kuşat Ol, Kevser; Oğlakçı, Ayşegül; Kartkaya, Kazım; Şentürk, Hakan

2014-01-01

Abstract We aim to study the effect of low-dose aspirin and kefir on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet. Forty adult male Sprague-Dawley rats were divided into five groups: control, high-salt (HS) (8.0% NaCl), HS+aspirin (10 mg/kg), HS+kefir (10.0%w/v), HS+aspirin +kefir. We measured sistolic blood pressure (SBP), mean arterial pressure (MAP), diastolic pressure, pulse pressure in the rats. Cathepsin B, L, DNA fragmentation and caspase-3 activities were determined from rat kidney tissues and rats clearance of creatinine calculated. Although HS diet increased significantly SBP, MAP, diastolic pressure, pulse pressure parameters compared the control values. They were not as high as accepted hypertension levels. When compared to HS groups, kefir groups significantly decrease Cathepsin B and DNA fragmentation levels. Caspase levels were elevated slightly in other groups according to control group. While, we also found that creatinine clearance was higher in HS+kefir and HS+low-dose aspirin than HS group. Thus, using low-dose aspirin had been approximately decreased of renal function damage. Kefir decreased renal function damage playing as Angiotensin-converting enzyme inhibitor. But, low-dose aspirin together with kefir worsened rat renal function damage. Cathepsin B might play role both apoptosis and prorenin-processing enzyme. But not caspase pathway may be involved in the present HS diet induced apoptosis. In conclusion, kefir and low-dose aspirin used independently protect renal function and renal damage induced by HS diet in rats.

Effects of dietary salt restriction on renal progression and interstitial fibrosis in adriamycin nephrosis.

PubMed

Park, Joon-Sung; Kim, Sua; Jo, Chor Ho; Oh, Il Hwan; Kim, Gheun-Ho

2014-01-01

Although high salt intake is thought to accelerate renal progression in proteinuric kidney disease, it is not known whether strict dietary salt restriction could delay renal inflammation and interstitial fibrosis. Here, we sought to answer this question in a rat model of adriamycin-induced nephrotic syndrome. Adriamycin was administered via the femoral vein in a single bolus (7.5 mg/kg), and the rats were put on a sodium-deficient rodent diet. Rats with intact kidneys were studied for 5 weeks (experiment 1), and uninephrectomized rats were studied for 6 weeks (experiment 2). In experiment 1, restricting salt intake improved renal tubulointerstitial histopathology in adriamycin-treated rats. Immunohistochemical and immunoblot results additionally showed that restricting dietary salt lowered adriamycin-induced expression of osteopontin, collagen III, and fibronectin. In experiment 2, salt restriction improved adriamycin-induced azotemia, although it did not affect proteinuria or blood pressure. Dietary salt restriction also reduced adriamycin-induced infiltration of ED1-positive cells and the upregulated expression of osteopontin and α-SMA. Masson's trichrome and Sirius red staining revealed that salt restriction slowed Adriamycin-induced progression of renal interstitial fibrosis. Finally, qPCR revealed that adriamycin-induced expression of TNF-α, IκB-α, gp91(phox), p47(phox), and p67(phox) mRNA was blocked by salt restriction. Our findings demonstrate that strict dietary salt restriction delays the progress of renal inflammation and fibrosis in proteinuric kidney disease, most likely via relieving the reactive oxygen species-mediated NF-κB activation. © 2014 S. Karger AG, Basel.

Simple and Sensitive Colorimetric Assay for Pb2+ Based on Glutathione Protected Ag Nanoparticles by Salt Amplification.

PubMed

Chen, Zhang; Li, Huidong; Chu, Lin; Liu, Chenbin; Luo, Shenglian

2015-02-01

A simple and sensitive colorimetric assay for Pb2+ detection has been reported using glutathione protected silver nanoparticles (AgNPs) by salt amplification. The naked AgNPs aggregate under the influence of salt. Glutathione (GSH) can bind to AgNPs via Ag-S bond, helping AgNPs to against salt-induced aggregation. However, GSH binding to AgNPs can be compromised by the interaction between Pb2+ and GSH. As a result, Pb2+-mediated aggregation of AgNPs under the influence of salt is reflected by the UV-Visible spectrum, and the qualitative and quantitative detection for Pb2+ is accomplished, with the detection range 0.5-4 µM and a detection limit of 0.5 µM. At the same time, Pb2+ in real water sample is detected. Furthermore, the high selectivity and low cost of the assay means it is promising for enviromental applications.

[An oral sensitization food allergy model in Brown-Norway rats].

PubMed

Huang, Juan; Zhong, Yan; Cai, Wei; Zhang, Hongbo

2009-01-01

To develop an oral-sensitized animal model of food allergy using Brown-Norway (BN) rats and evaluate the sensitivity of ELISA and passive cutaneous anaphylaxis (PCA) in detecting ovalbumin-specific IgE antibody (OVA-IgE) level in sensitized animals. Sixteen 3-week old female BN rats were randomly divided into 3 groups: negative control group orally gavaged with saline, positive control group sensitized by intraperitoneal injection of 0. lmg/d OVA, and, study group sensitized by daily gavage of 1 mg/d ovalbumin (OVA). OVA-IgE was analyzed by ELISA and PCA method at week 4, 5, 6, 7, 8 and 9. At week 13, OVA-IgE level was analyzed after orally challenged by 1.0 ml of 100 mg/ml OVA. The ELISA result showed that the OVA-IgE level in study group was significantly increased at week 6, 7 and week 8 compared with negative control group (P < 0.05), and the highest level was found at week 6. There was no significant difference for the level of OVA-IgE between study group and positive control group. The sensitization rate in study group was 60%, 80% and 80% at week 6, 7 and 8 respectively, which was similar to positive control group. All PCA results in study group were negative, while in positive control group it was positive. Oral sensitization could be used as a suitable method to establish an animal model of food allergy, which is more comparable with the natural sensitization process in food allergy patients. ELISA method is more sensitive in detecting OVA-IgE level in oral sensitized animal model than PCA method.

Rats free to select between pure protein and a fat-carbohydrate mix ingest high-protein mixed meals during the dark period and protein meals during the light period.

PubMed

Makarios-Lahham, Lina; Roseau, Suzanne M; Fromentin, Gilles; Tome, Daniel; Even, Patrick C

2004-03-01

Rats that are allowed to select their diets [dietary self- selection (DSS)] often ingest >30% of their daily energy in the form of protein. Such an intake may seem unhealthy, but the consistency of this choice suggests that it is motivated by physiologic drives. To gain a clearer understanding of how protein selection is structured during DSS, we adapted 12 rats to a standard diet (14% Protein) and then allowed them to choose between two diets, i.e., total milk protein (P) and a mix of carbohydrates and lipids (FC). The protein intake during DSS rose above 40%; assuming an intermeal interval of 10 min, 70% of the energy intake occurred with meals that included both P and FC, with the sequence of FC followed by P preferred to the sequence of P followed by FC (70 vs. 30%, P < 0.001). In addition, energy intake during the light period was reduced to only 10% of the daily energy intake [vs. 30% with the control P14 diet or a with a high-protein diet (50%)], and 90% of the intake was in the form of pure protein meals. In complementary studies, we verified that the high protein intake also occurred when rats were offered casein and whey and was not due to the high palatability of the milk protein. We conclude that a specific feeding pattern accompanies high protein intake in rats allowed DSS. The mechanisms underlying this behavior and its potential beneficial/adverse consequences over the long term still must be clarified.

Extraction, scrub, and strip test results for the solvent transfer to salt waste processing facility

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

Peters, T.

The Savannah River National Laboratory (SRNL) prepared approximately 240 gallons of Caustic-Side Solvent Extraction (CSSX) solvent for use at the Salt Waste Processing Facility (SWPF). An Extraction, Scrub, and Strip (ESS) test was performed on a sample of the prepared solvent using a salt solution prepared by Parsons to determine cesium distribution ratios (D(Cs)), and cesium concentration in the strip effluent (SE) and decontaminated salt solution (DSS) streams. This data will be used by Parsons to help qualify the solvent for use at the SWPF. The ESS test showed acceptable performance of the solvent for extraction, scrub, and strip operations.more » The extraction D(Cs) measured 15.5, exceeding the required value of 8. This value is consistent with results from previous ESS tests using similar solvent formulations. Similarly, scrub and strip cesium distribution ratios fell within acceptable ranges.« less

Effects of Tribulus terrestris on endocrine sensitive organs in male and female Wistar rats.

PubMed

Martino-Andrade, Anderson J; Morais, Rosana N; Spercoski, Katherinne M; Rossi, Stefani C; Vechi, Marina F; Golin, Munisa; Lombardi, Natália F; Greca, Cláudio S; Dalsenter, Paulo R

2010-01-08

Investigate the possible effects of Tribulus terrestris (TT) on endocrine sensitive organs in intact and castrated male rats as well as in a post-menopausal rat model using ovariectomized females. Three different dose levels of TT (11, 42 and 110 mg/kg/day) were administered to castrated males for 7 days and to intact males and castrated females for 28 days. In addition to TT treatment, all experiments also included a group of rats treated with dehydroepiandrosterone (DHEA). In experiments using castrated males and females we also used testosterone and 17 alpha-ethynylestradiol, respectively, as positive controls for androgenicity and estrogenicity. Neither DHEA nor TT was able to stimulate androgen sensitive tissues like the prostate and seminal vesicle in both intact and castrated male rats. In addition, administration of TT to intact male rats for 28 days did not change serum testosterone levels as well as did not produce any quantitative change in the fecal excretion of androgenic metabolites. However, a slight increase in the number of homogenization-resistant spermatids was observed in rats treated with 11 mg/kg/day of TT extract. In ovariectomized females, TT did not produce any stimulatory effects in uterine and vaginal epithelia. Tribulus terrestris was not able to stimulate endocrine sensitive tissues such as the prostate, seminal vesicle, uterus and vagina in Wistar rats, indicating lack of androgenic and estrogenic activity in vivo. We also showed a positive effect of TT administration on rat sperm production, associated with unchanged levels of circulating androgens. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

The DSS-14 C-band exciter

NASA Technical Reports Server (NTRS)

Rowan, D. R.

1989-01-01

The development and implementation of a C-band exciter for use with the Block IV Receiver-Exciter Subsystem at Deep Space Station 14 (DSS-14) has been completed. The exciter supplements the standard capabilities of the Block IV system by providing a drive signal for the C-band transmitter while generating coherent translation frequencies for C-band (5-GHz) to S-band (2.2- to 2.3-GHz) Doppler extraction, C-band to L-band (1.6-GHz) zero delay measurements, and a level calibrated L-band test signal. Exciter functions are described, and a general explanation and description of the C-band uplink controller is presented.

Cardiovascular effects of Helichrysum ceres S Moore [Asteraceae] ethanolic leaf extract in some experimental animal paradigms

PubMed Central

Musabayane, Cephas T; Kamadyaapa, Dave R; Gondwe, Mavuto; Moodley, Kogi; Ojewole, John AO

2008-01-01

Summary Summary The aim of this study was to examine some in vivo and in vitro cardiovascular effects of Helichrysum ceres leaf ethanolic extract (HCE) in experimental animal paradigms. The acute effects of HCE on blood pressure were studied in anaesthetised normotensive male Wistar rats challenged with intravenous hypotonic saline infusion after a 3.5-hour equilibration for four hours of one-hour control, 1.5-hour treatment and 1.5-hour recovery periods. HCE was added to the infusate during the treatment period. Sub-chronic hypotensive effects of HCE were examined in weanling Dahl salt-sensitive (DSS) genetically hypertensive rats, which progressively develop hypertension with age, treated with HCE (80 mg/kg) every third consecutive day for seven weeks. Isolated atrial muscle strips, portal veins and descending thoracic aortic rings of healthy normotensive Wistar rats were used to investigate the vascular effects of HCE. Acute HCE administration caused a significant (p < 0.05) fall in blood pressure in the normotensive anaesthetised Wistar rats. DSS hypertensive rats treated with HCE displayed low arterial blood pressure and heart rate values from weeks five to seven. HCE produced concentration-dependent negative inotropic and chronotropic effects on rat isolated electrically driven left, and spontaneously beating right atrial muscle preparations, respectively. HCE also evoked concentration-dependent relaxation responses of endothelium-intact aortic rings and portal veins isolated from healthy normotensive Wistar rats. The vasorelaxant effects of HCE in intact aortic rings were significantly reduced, but not completely abolished by adding endothelial-derived factor (EDRF) inhibitor, L-NAME, suggesting that the vasorelaxant effect of the extract is mediated via EDRF-dependent and independent mechanisms. The results of the study suggest that the hypotensive action of HCE is elicited, in part, directly by decreasing myocardial contractile performance and total

"When the going gets tough, who keeps going?" Depletion sensitivity moderates the ego-depletion effect.

PubMed

Salmon, Stefanie J; Adriaanse, Marieke A; De Vet, Emely; Fennis, Bob M; De Ridder, Denise T D

2014-01-01

Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion.

Validation of simple indexes to assess insulin sensitivity during pregnancy in Wistar and Sprague-Dawley rats.

PubMed

Cacho, J; Sevillano, J; de Castro, J; Herrera, E; Ramos, M P

2008-11-01

Insulin resistance plays a role in the pathogenesis of diabetes, including gestational diabetes. The glucose clamp is considered the gold standard for determining in vivo insulin sensitivity, both in human and in animal models. However, the clamp is laborious, time consuming and, in animals, requires anesthesia and collection of multiple blood samples. In human studies, a number of simple indexes, derived from fasting glucose and insulin levels, have been obtained and validated against the glucose clamp. However, these indexes have not been validated in rats and their accuracy in predicting altered insulin sensitivity remains to be established. In the present study, we have evaluated whether indirect estimates based on fasting glucose and insulin levels are valid predictors of insulin sensitivity in nonpregnant and 20-day-pregnant Wistar and Sprague-Dawley rats. We have analyzed the homeostasis model assessment of insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI), and the fasting glucose-to-insulin ratio (FGIR) by comparing them with the insulin sensitivity (SI(Clamp)) values obtained during the hyperinsulinemic-isoglycemic clamp. We have performed a calibration analysis to evaluate the ability of these indexes to accurately predict insulin sensitivity as determined by the reference glucose clamp. Finally, to assess the reliability of these indexes for the identification of animals with impaired insulin sensitivity, performance of the indexes was analyzed by receiver operating characteristic (ROC) curves in Wistar and Sprague-Dawley rats. We found that HOMA-IR, QUICKI, and FGIR correlated significantly with SI(Clamp), exhibited good sensitivity and specificity, accurately predicted SI(Clamp), and yielded lower insulin sensitivity in pregnant than in nonpregnant rats. Together, our data demonstrate that these indexes provide an easy and accurate measure of insulin sensitivity during pregnancy in the rat.

Rats bred for high alcohol drinking are more sensitive to delayed and probabilistic outcomes.

PubMed

Wilhelm, C J; Mitchell, S H

2008-10-01

Alcoholics and heavy drinkers score higher on measures of impulsivity than nonalcoholics and light drinkers. This may be because of factors that predate drug exposure (e.g. genetics). This study examined the role of genetics by comparing impulsivity measures in ethanol-naive rats selectively bred based on their high [high alcohol drinking (HAD)] or low [low alcohol drinking (LAD)] consumption of ethanol. Replicates 1 and 2 of the HAD and LAD rats, developed by the University of Indiana Alcohol Research Center, completed two different discounting tasks. Delay discounting examines sensitivity to rewards that are delayed in time and is commonly used to assess 'choice' impulsivity. Probability discounting examines sensitivity to the uncertain delivery of rewards and has been used to assess risk taking and risk assessment. High alcohol drinking rats discounted delayed and probabilistic rewards more steeply than LAD rats. Discount rates associated with probabilistic and delayed rewards were weakly correlated, while bias was strongly correlated with discount rate in both delay and probability discounting. The results suggest that selective breeding for high alcohol consumption selects for animals that are more sensitive to delayed and probabilistic outcomes. Sensitivity to delayed or probabilistic outcomes may be predictive of future drinking in genetically predisposed individuals.

Eating high fat chow increases the sensitivity of rats to 8-OH-DPAT-induced lower lip retraction.

PubMed

Li, Jun-Xu; Ju, Shutian; Baladi, Michelle G; Koek, Wouter; France, Charles P

2011-12-01

Eating high fat food can alter sensitivity to drugs acting on dopamine systems; this study examined whether eating high fat food alters sensitivity to a drug acting on serotonin (5-HT) systems. Sensitivity to (+)-8-hydroxy-2-(dipropylamino) tetralin hydrobromide (8-OH-DPAT; 5-HT1A receptor agonist)-induced lower lip retraction was examined in separate groups (n=8-9) of rats with free access to standard (5.7% fat) or high fat (34.3% fat) chow; sensitivity to quinpirole (dopamine D3/D2 receptor agonist)-induced yawning was also examined. Rats eating high fat chow gained more body weight than rats eating standard chow and, after 6 weeks of eating high fat chow, they were more sensitive to 8-OH-DPAT (0.01-0.1 mg/kg)-induced lower lip retraction and quinpirole (0.0032-0.32 mg/kg)-induced yawning. These changes were not reversed when rats that previously ate high fat chow were switched to eating standard chow and sensitivity to 8-OH-DPAT and quinpirole increased when rats that previously ate standard chow ate high fat chow. These data extend previous results showing changes in sensitivity to drugs acting on dopamine systems in animals eating high fat chow to a drug acting at 5-HT1A receptors and they provide support for the notion that eating certain foods impacts sensitivity to drugs acting on monoamine systems.

Eating high fat chow increases the sensitivity of rats to 8-OH-DPAT-induced lower lip retraction

PubMed Central

Li, Jun-Xu; Ju, Shutian; Baladi, Michelle G; Koek, Wouter; France, Charles P

2011-01-01

Eating high fat food can alter sensitivity to drugs acting on dopamine systems; this study examined whether eating high fat food alters sensitivity to a drug acting on serotonin (5-HT) systems. Sensitivity to (+)-8-hydroxy-2-(dipropylamino) tetralin hydrobromide (8-OH-DPAT; 5-HT1A receptor agonist)-induced lower lip retraction was examined in separate groups (n=8-9) of rats with free access to standard (5.7% fat) or high fat (34.3% fat) chow; sensitivity to quinpirole (dopamine D3/D2 receptor agonist)-induced yawning was also examined. Rats eating high fat chow gained more body weight than rats eating standard chow and, after 6 weeks of eating high fat chow, they were more sensitive to 8-OH-DPAT (0.01-0.1 mg/kg)-induced lower lip retraction and quinpirole (0.0032-0.32 mg/kg)-induced yawning. These changes were not reversed when rats that previously ate high fat chow were switched to eating standard chow and sensitivity to 8-OH-DPAT and quinpirole increased when rats that previously ate standard chow ate high fat chow. These data extend previous results showing changes in sensitivity to drugs acting on dopamine systems in animals eating high fat chow to a drug acting at 5-HT1A receptors and they provide support for the notion that eating certain foods impacts sensitivity to drugs acting on monoamine systems. PMID:21979831

The Influence of Ghrelin on the Development of Dextran Sodium Sulfate-Induced Colitis in Rats

PubMed Central

Matuszyk, Aleksandra; Ceranowicz, Dagmara; Warzecha, Zygmunt; Ceranowicz, Piotr; Fyderek, Krzysztof; Gałązka, Krystyna; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Pihut, Małgorzata; Dembiński, Artur

2015-01-01

Ghrelin has protective and therapeutic effects in the gut. The aim of present studies was to investigate the effect of treatment with ghrelin on the development of colitis evoked by dextran sodium sulfate (DSS). Methods. Studies have been performed on rats. Colitis was induced by adding 5% DSS to the drinking water for 5 days. During this period animals were treated intraperitoneally twice a day with saline or ghrelin given at the dose of 8 nmol/kg/dose. On the sixth day, animals were anesthetized and the severity of colitis was assessed. Results. Treatment with ghrelin during administration of DSS reduced the development of colitis. Morphological features of colonic mucosa exhibited a reduction in the area and deep of mucosal damage. Ghrelin reversed the colitis-induced decrease in blood flow, DNA synthesis, and superoxide dismutase activity in colonic mucosa. These effects were accompanied by a decrease in the colitis-evoked increase in mucosal concentration of interleukin-1β and malondialdehyde. Treatment with ghrelin reversed the DSS-induced reduction in body weight gain. Conclusions. Administration of ghrelin exhibits the preventive effect against the development of DSS-induced colitis. This effect seems to be related to ghrelin's anti-inflammatory and antioxidative properties. PMID:26713317

Defective renal dopamine function and sodium-sensitive hypertension in adult ovariectomized Wistar rats: role of the cytochrome P-450 pathway.

PubMed

Di Ciano, Luis A; Azurmendi, Pablo J; Colombero, Cecilia; Levin, Gloria; Oddo, Elisabet M; Arrizurieta, Elvira E; Nowicki, Susana; Ibarra, Fernando R

2015-06-15

We have previously shown that ovariectomy in adult Wistar rats under normal sodium (NS) intake results in an overexpression of the total Na(+)-K(+)-ATPase (NKA) α1-subunit (Di Ciano LA, Azurmendi PJ, Toledo JE, Oddo EM, Zotta E, Ochoa F, Arrizurieta EE, Ibarra FR. Clin Exp Hypertens 35: 475-483, 2013). Upon high sodium (HS) intake, ovariectomized (oVx) rats developed defective NKA phosphorylation, a decrease in sodium excretion, and an increment in mean blood pressure (MBP). Since NKA phosphorylation is modulated by dopamine (DA), the aim of this study was to compare the intracellular response of the renal DA system leading to NKA phosphorylation upon sodium challenge in intact female (IF) and oVx rats. In IF rats, HS caused an increase in urinary DA and sodium, in NKA phosphorylation state, in cytochrome P-4504A (CYP4A) expression, and in 20-HETE production, while MBP kept normal. Blockade of the D1 receptor (D1R) with the D1-like receptor antagonist SCH 23390 in IFHS rats shifted NKA into a more dephosphorylated state, decreased sodium excretion by 50%, and increased MBP. In oVxNS rats, D1R expression was reduced and D3R expression was increased, and under HS intake sodium excretion was lower and MBP higher than in IFHS rats (both P < 0.05), NKA was more dephosphorylated than in IFHS, and CYP4A expression or 20-HETE production did not change. Blockade of D1R in oVxHS rats changed neither NKA phosphorylation state nor sodium excretion or MBP. D2R and PKCα expression did not vary among groups. The alteration of the renal DA system produced by ovariectomy could account for the defective NKA phosphorylation, the inefficient excretion of sodium load, and the development of salt-sensitive hypertension. Copyright © 2015 the American Physiological Society.

Transdermal Bioavailability in Rats of Lidocaine in the Forms of Ionic Liquids, Salts, and Deep Eutectic.

PubMed

Berton, Paula; Di Bona, Kristin R; Yancey, Denise; Rizvi, Syed A A; Gray, Marquita; Gurau, Gabriela; Shamshina, Julia L; Rasco, Jane F; Rogers, Robin D

2017-05-11

Tuning the bioavailability of lidocaine was explored by its incorporation into the ionic liquid lidocainium docusate ([Lid][Doc]) and the deep eutectic Lidocaine·Ibuprofen (Lid·Ibu) and comparing the transdermal absorption of these with the crystalline salt lidocainium chloride ([Lid]Cl). Each form of lidocaine was dissolved in a vehicle cream and topically applied to Sprague-Dawley rats. The concentrations of the active pharmaceutical ingredients (APIs) in blood plasma were monitored over time as an indication of systemic absorption. The concentration of lidocaine in plasma varied between applied API-based creams, with faster and higher systemic absorption of the hydrogen bonded deep eutectic Lid·Ibu than the absorption of the salts [Lid]Cl or [Lid][Doc]. Interestingly, a differential transdermal absorption was observed between lidocaine and ibuprofen when Lid·Ibu was applied, possibly indicating different interactions with the tissue components.

Transdermal Bioavailability in Rats of Lidocaine in the Forms of Ionic Liquids, Salts, and Deep Eutectic

PubMed Central

2017-01-01

Tuning the bioavailability of lidocaine was explored by its incorporation into the ionic liquid lidocainium docusate ([Lid][Doc]) and the deep eutectic Lidocaine·Ibuprofen (Lid·Ibu) and comparing the transdermal absorption of these with the crystalline salt lidocainium chloride ([Lid]Cl). Each form of lidocaine was dissolved in a vehicle cream and topically applied to Sprague–Dawley rats. The concentrations of the active pharmaceutical ingredients (APIs) in blood plasma were monitored over time as an indication of systemic absorption. The concentration of lidocaine in plasma varied between applied API-based creams, with faster and higher systemic absorption of the hydrogen bonded deep eutectic Lid·Ibu than the absorption of the salts [Lid]Cl or [Lid][Doc]. Interestingly, a differential transdermal absorption was observed between lidocaine and ibuprofen when Lid·Ibu was applied, possibly indicating different interactions with the tissue components. PMID:28523100

Bile Salt Homeostasis in Normal and Bsep Gene Knockout Rats with Single and Repeated Doses of Troglitazone.

PubMed

Cheng, Yaofeng; Chen, Shenjue; Freeden, Chris; Chen, Weiqi; Zhang, Yueping; Abraham, Pamela; Nelson, David M; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

2017-09-01

The interference of bile acid secretion through bile salt export pump (BSEP) inhibition is one of the mechanisms for troglitazone (TGZ)-induced hepatotoxicity. Here, we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep knockout (KO) rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on day 1 and day 7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7.6- and 9.3-fold lower than in WT on day 1 and day 7, respectively, due to increased TS biliary excretion. With Bsep KO, the mRNA levels of multidrug resistance-associated protein 2 (Mrp2), Mrp3, Mrp4, Mdr1, breast cancer resistance protein (Bcrp), sodium taurocholate cotransporting polypeptide, small heterodimer partner, and Sult2A1 were significantly altered in KO rats. Following seven daily TGZ treatments, Cyp7A1 was significantly increased in both WT and KO rats. In the vehicle groups, plasma exposures of individual bile acids demonstrated variable changes in KO rats as compared with WT. WT rats dosed with TGZ showed an increase of many bile acid species in plasma on day 1, suggesting the inhibition of Bsep. Conversely, these changes returned to base levels on day 7. In KO rats, alterations of most bile acids were observed after seven doses of TGZ. Collectively, bile acid homeostasis in rats was regulated through bile acid synthesis and transport in response to Bsep deficiency and TGZ inhibition. Additionally, our study is the first to demonstrate that repeated TGZ doses can upregulate Cyp7A1 in rats. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Eating high fat chow increases the sensitivity of rats to quinpirole-induced discriminative stimulus effects and yawning

PubMed Central

Baladi, Michelle G; France, Charles P

2010-01-01

Discriminative stimulus effects of directly-acting dopamine receptor agonists (e.g. quinpirole) appear to be mediated by D3 receptors in free-feeding rats. Free access to high fat chow increases sensitivity to quinpirole-induced yawning and the current study examined whether eating high fat chow increases sensitivity to the discriminative stimulus effects of quinpirole. Five rats discriminated between 0.032 mg/kg quinpirole and vehicle while responding under a continuous reinforcement schedule of stimulus shock termination. When rats had free access to high fat chow (discrimination training was suspended), the quinpirole discrimination dose-response curve shifted leftward, possibly indicating enhanced sensitivity at D3 receptors. In the same rats, both the ascending (mediated by D3 receptors) and descending (mediated by D2 receptors) limbs of the dose- response curve for quinpirole-induced yawning shifted leftward. When rats had free access to a standard chow (discrimination training was suspended), the quinpirole discrimination and yawning dose-response curves did not change. Together with published data showing that the discriminative stimulus effects of quinpirole in free- feeding rats are mediated by D3 receptors and the insensitivity of this effect of quinpirole to food restriction (shown to increase sensitivity to D2 but not D3-mediated effects), these results suggest that the leftward shift of the discrimination dose-response curve when rats eat high fat chow is likely due to enhanced sensitivity at D3 receptors. Thus, eating high fat food enhances drug effects in a manner that might impact clinical effects of drugs or vulnerability to drug abuse. PMID:20729718

Eating high-fat chow increases the sensitivity of rats to quinpirole-induced discriminative stimulus effects and yawning.

PubMed

Baladi, Michelle G; France, Charles P

2010-10-01

Discriminative stimulus effects of direct acting dopamine receptor agonists (e.g. quinpirole) appear to be mediated by D3 receptors in free-feeding rats. Free access to high-fat chow increases sensitivity to quinpirole-induced yawning, and this study examined whether eating high-fat chow increases sensitivity to the discriminative stimulus effects of quinpirole. Five rats discriminated between 0.032 mg/kg quinpirole and vehicle while responding under a continuous reinforcement schedule of stimulus shock termination. When rats had free access to high-fat chow (discrimination training was suspended), the quinpirole discrimination dose-response curve shifted leftward, possibly indicating enhanced sensitivity at D3 receptors. In the same rats, both the ascending (mediated by D3 receptors) and descending (mediated by D2 receptors) limbs of the dose-response curve for quinpirole-induced yawning shifted leftward. When rats had free access to a standard chow (discrimination training was suspended), the quinpirole discrimination and yawning dose-response curves did not change. Together with published data showing that the discriminative stimulus effects of quinpirole in free-feeding rats are mediated by D3 receptors and the insensitivity of this effect of quinpirole to food restriction (shown to increase sensitivity to D2 but not D3-mediated effects), these results suggest that the leftward shift of the discrimination dose-response curve when rats eat high-fat chow is likely because of enhanced sensitivity at D3 receptors. Thus, eating high-fat food enhances drug effects in a manner that might impact clinical effects of drugs or vulnerability to drug abuse.

Mitochondrial ryanodine-sensitive Ca2+ channels of rat liver.

PubMed

Kupynyak, N I; Ikkert, O V; Shlykov, S G; Babich, L G; Manko, V V

2017-01-01

To examine ryanodine-sensitive Ca 2+ channels in mitochondria of rat hepatocytes and their role in energy state of the cells via investigation of the ryanodine effect on mitochondrial membrane potential. Oxygen consumption was measured by polarography using the Clark electrode. The substrates of oxidation such as pyruvate (5mM), α-ketoglutarate (5mM), or succinate (5mM) were used. Oxidative phosphorylation was stimulated by the addition of adenosine diphosphate (200nM). Mitochondrial membrane potential was measured using a voltage-sensitive fluorescent probe tetramethylrhodamine-methyl-ester (0.1μM) and was analyzed by a flow cytometer. To evaluate the intact mitochondria, we used carbonil cyanide m-chlorophenyl hydrazone (CCCP, 10μM). Changes in the ionized calcium concentration in rat liver mitochondria were measured using a fluorescent probe Fluo-4 AM. Effect of ryanodine on oxygen consumption of rat liver mitochondria depends on the oxidation substrate and the incubation time. Oxidation of pyruvate in the presence of ryanodine (0.05μM) decreased the membrane potential of rat liver mitochondria by 38.4%. At higher concentrations, ryanodine (0.1μM or 1μM) led to decrease of membrane potential by 51.7% and 42.8%, respectively. In contrast, oxidation of α-ketoglutarate in the presence of ryanodine (0.05μM) increased mitochondrial membrane potential by 16.8%. However, at higher concentrations, ryanodine (0.1μM or 1μM) triggered a decreasing of membrane potential by 42.5% and 31.0%, respectively. Therefore, ryanodine at various concentrations (0.05μM, 0.1μM, or 1μM) causes differential effects on Ca 2+ concentration in the mitochondria matrix under oxidation of pyruvate or α-ketoglutarate. The data suggest the presence of ryanodine receptors in mitochondrial membrane of rat hepatocytes. Their inhibition with higher concentrations of ryanodine leads to decreasing of intra-mitochondrial Ca 2+ concentration and affecting the energy state of mictochondria

Mechanisms of disease: the role of GRK4 in the etiology of essential hypertension and salt sensitivity.

PubMed

Felder, Robin A; Jose, Pedro A

2006-11-01

Hypertension and salt sensitivity of blood pressure are two conditions the etiologies of which are still elusive because of the complex influences of genes, environment, and behavior. Recent understanding of the molecular mechanisms that govern sodium homeostasis is shedding new light on how genes, their protein products, and interacting metabolic pathways contribute to disease. Sodium transport is increased in the proximal tubule and thick ascending limb of Henle of the kidney in human essential hypertension. This Review focuses on the counter-regulation between the dopaminergic and renin-angiotensin systems in the renal proximal tubule, which is the site of about 70% of total renal sodium reabsorption. The inhibitory effect of dopamine is most evident under conditions of moderate sodium excess, whereas the stimulatory effect of angiotensin II is most evident under conditions of sodium deficit. Dopamine and angiotensin II exert their actions via G protein-coupled receptors, which are in turn regulated by G protein-coupled receptor kinases (GRKs). Polymorphisms that lead to aberrant action of GRKs cause a number of conditions, including hypertension and salt sensitivity. Polymorphisms in one particular member of this family-GRK4-have been shown to cause hyperphosphorylation, desensitization and internalization of a member of the dopamine receptor family, the dopamine 1 receptor, while increasing the expression of a key receptor of the renin-angiotensin system, the angiotensin II type 1 receptor. Novel diagnostic and therapeutic approaches for identifying at-risk subjects, followed by selective treatment of hypertension and salt sensitivity, might center on restoring normal receptor function through blocking the effects of GRK4 polymorphisms.

Noopept reduces the postischemic functional and metabolic disorders in the brain of rats with different sensitivity to hypoxia.

PubMed

Zarubina, I V; Shabanov, P D

2009-03-01

Chronic cerebral ischemia was induced by ligation of both common carotid arteries in Wistar rats, divided by sensitivity to hypoxia into highly sensitive and low-sensitive. Noopept (peptide preparation), injected (0.5 mg/kg) during 7 days after occlusion of the carotid arteries, reduced the neurological disorders in rats with high and low sensitivity to hypoxia and improved their survival during the postischemic period. Noopept normalized behavior disordered by cerebral ischemia (according to the open field and elevated plus maze tests), prevented accumulation of LPO products and inhibition of antioxidant systems in the brain of rats with high and low sensitivity to hypoxia. Hence, noopept exhibited a neuroprotective effect in cerebral ischemia.

CYP3A variation and the evolution of salt-sensitivity variants.

PubMed

Thompson, E E; Kuttab-Boulos, H; Witonsky, D; Yang, L; Roe, B A; Di Rienzo, A

2004-12-01

Members of the cytochrome P450 3A subfamily catalyze the metabolism of endogenous substrates, environmental carcinogens, and clinically important exogenous compounds, such as prescription drugs and therapeutic agents. In particular, the CYP3A4 and CYP3A5 genes play an especially important role in pharmacogenetics, since they metabolize >50% of the drugs on the market. However, known genetic variants at these two loci are not sufficient to account for the observed phenotypic variability in drug response. We used a comparative genomics approach to identify conserved coding and noncoding regions at these genes and resequenced them in three ethnically diverse human populations. We show that remarkable interpopulation differences exist with regard to frequency spectrum and haplotype structure. The non-African samples are characterized by a marked excess of rare variants and the presence of a homogeneous group of long-range haplotypes at high frequency. The CYP3A5*1/*3 polymorphism, which is likely to influence salt and water retention and risk for salt-sensitive hypertension, was genotyped in >1,000 individuals from 52 worldwide population samples. The results reveal an unusual geographic pattern whereby the CYP3A5*3 frequency shows extreme variation across human populations and is significantly correlated with distance from the equator. Furthermore, we show that an unlinked variant, AGT M235T, previously implicated in hypertension and pre-eclampsia, exhibits a similar geographic distribution and is significantly correlated in frequency with CYP3A5*1/*3. Taken together, these results suggest that variants that influence salt homeostasis were the targets of a shared selective pressure that resulted from an environmental variable correlated with latitude.

CYP3A Variation and the Evolution of Salt-Sensitivity Variants

PubMed Central

Thompson, E. E.; Kuttab-Boulos, H.; Witonsky, D.; Yang, L.; Roe, B. A.; Di Rienzo, A.

2004-01-01

Members of the cytochrome P450 3A subfamily catalyze the metabolism of endogenous substrates, environmental carcinogens, and clinically important exogenous compounds, such as prescription drugs and therapeutic agents. In particular, the CYP3A4 and CYP3A5 genes play an especially important role in pharmacogenetics, since they metabolize >50% of the drugs on the market. However, known genetic variants at these two loci are not sufficient to account for the observed phenotypic variability in drug response. We used a comparative genomics approach to identify conserved coding and noncoding regions at these genes and resequenced them in three ethnically diverse human populations. We show that remarkable interpopulation differences exist with regard to frequency spectrum and haplotype structure. The non-African samples are characterized by a marked excess of rare variants and the presence of a homogeneous group of long-range haplotypes at high frequency. The CYP3A5*1/*3 polymorphism, which is likely to influence salt and water retention and risk for salt-sensitive hypertension, was genotyped in >1,000 individuals from 52 worldwide population samples. The results reveal an unusual geographic pattern whereby the CYP3A5*3 frequency shows extreme variation across human populations and is significantly correlated with distance from the equator. Furthermore, we show that an unlinked variant, AGT M235T, previously implicated in hypertension and pre-eclampsia, exhibits a similar geographic distribution and is significantly correlated in frequency with CYP3A5*1/*3. Taken together, these results suggest that variants that influence salt homeostasis were the targets of a shared selective pressure that resulted from an environmental variable correlated with latitude. PMID:15492926

Stress-sensitive arterial hypertension, haemodynamic changes and brain metabolites in hypertensive ISIAH rats: MRI investigation.

PubMed

Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel, A L; Akulov, A E

2017-05-01

What is the central question of this study? Stress-sensitive arterial hypertension is considered to be controlled by changes in central and peripheral sympathetic regulating mechanisms, which eventually result in haemodynamic alterations and blood pressure elevation. Therefore, study of the early stages of development of hypertension is of particular interest, because it helps in understanding the aetiology of the disease. What is the main finding and its importance? Non-invasive in vivo investigation in ISIAH rats demonstrated that establishment of sustainable stress-sensitive hypertension is accompanied by a decrease in prefrontal cortex activity and mobilization of hypothalamic processes, with considerable correlations between haemodynamic parameters and individual metabolite ratios. The study of early development of arterial hypertension in association with emotional stress is of great importance for better understanding of the aetiology and pathogenesis of the hypertensive disease. Magnetic resonance imaging (MRI) was applied to evaluate the changes in haemodynamics and brain metabolites in 1- and 3-month-old inherited stress-induced arterial hypertension (ISIAH) rats (10 male rats) with stress-sensitive arterial hypertension and in control normotensive Wistar Albino Glaxo (WAG) rats (eight male rats). In the 3-month-old ISIAH rats, the age-dependent increase in blood pressure was associated with increased blood flow through the renal arteries and decreased blood flow in the lower part of the abdominal aorta. The renal vascular resistance in the ISIAH rats decreased during ageing, although at both ages it remained higher than the renal vascular resistance in WAG rats. An integral metabolome portrait demonstrated that development of hypertension in the ISIAH rats was associated with an attenuation of the excitatory and energetic activity in the prefrontal cortex, whereas in the WAG rats the opposite age-dependent changes were observed. In contrast, in the

High salt intake increases plasma trimethylamine N-oxide (TMAO) concentration and produces gut dysbiosis in rats.

PubMed

Bielinska, Klaudia; Radkowski, Marek; Grochowska, Marta; Perlejewski, Karol; Huc, Tomasz; Jaworska, Kinga; Motooka, Daisuke; Nakamura, Shota; Ufnal, Marcin

2018-03-22

A high-salt diet is considered a cardiovascular risk factor; however, the mechanisms are not clear. Research suggests that gut bacteria-derived metabolites such as trimethylamine N-oxide (TMAO) are markers of cardiovascular diseases. We evaluated the effect of high salt intake on gut bacteria and their metabolites plasma level. Sprague Dawley rats ages 12-14 wk were maintained on either water (controls) or 0.9% or 2% sodium chloride (NaCl) water solution (isotonic and hypertonic groups, respectively) for 2 wk. Blood plasma, urine, and stool samples were analyzed for concentrations of trimethylamine (TMA; a TMAO precursor), TMAO, and indoxyl sulfate (indole metabolite). The gut-blood barrier permeability to TMA and TMA liver clearance were assessed at baseline and after TMA intracolonic challenge test. Gut bacterial flora was analyzed with a 16S ribosomal ribonucleic acid (rRNA) gene sequence analysis. The isotonic and hypertonic groups showed a significantly higher plasma TMAO and significantly lower 24-hr TMAO urine excretion than the controls. However, the TMA stool level was similar between the groups. There was no significant difference between the groups in gut-blood barrier permeability and TMA liver clearance. Plasma indoxyl concentration and 24-hr urine indoxyl excretion were similar between the groups. There was a significant difference between the groups in gut bacteria composition. High salt intake increases plasma TMAO concentration, which is associated with decreased TMAO urine excretion. Furthermore, high salt intake alters gut bacteria composition. These findings suggest that salt intake affects an interplay between gut bacteria and their host homeostasis. Copyright © 2018 Elsevier Inc. All rights reserved.

Role of glycogen synthase kinase-3β and PPAR-γ on epithelial-to-mesenchymal transition in DSS-induced colorectal fibrosis.

PubMed

Di Gregorio, Jacopo; Sferra, Roberta; Speca, Silvia; Vetuschi, Antonella; Dubuquoy, Caroline; Desreumaux, Pierre; Pompili, Simona; Cristiano, Loredana; Gaudio, Eugenio; Flati, Vincenzo; Latella, Giovanni

2017-01-01

Intestinal fibrosis is characterized by abnormal production and deposition of extracellular matrix (ECM) proteins by activated myofibroblasts. The main progenitor cells of activated myofibroblasts are the fibroblasts and the epithelial cells, the latter through the epithelial-mesenchymal transition (EMT). To evaluate the action of the new PPAR-γ modulator, GED-0507-34 Levo (GED) on the expression of EMT associated and regulatory proteins such as TGF-β, Smad3, E-cadherin, Snail, ZEB1, β-catenin, and GSK-3β, in a mouse model of DSS-induced intestinal fibrosis. Chronic colitis and fibrosis were induced by oral administration of 2.5% DSS (w/v) for 6 weeks. GW9662 (GW), a selective PPAR-γ inhibitor, was also administered by intraperitoneal injection at the dose of 1 mg/kg/day combined with GED treatment. All drugs were administered at the beginning of the second cycle of DSS (day 12). 65 mice were randomly divided into five groups (H2O as controls n = 10, H2O+GED n = 10, DSS n = 15, DSS+GED n = 15, DSS+GED+GW n = 15). The colon was excised for macroscopic examination and histological and morphometric analyses. The level of expression of molecules involved in EMT and fibrosis, like TGF-β, Smad3, E-cadherin, Snail, ZEB1, β-catenin, GSK-3β and PPAR-γ, was assessed by immunohistochemistry, immunofluorescence, western blot and Real Time PCR. GED improved the DSS-induced chronic colitis and fibrosis. GED was able to reduce the expression of the main fibrosis markers (α-SMA, collagen I-III and fibronectin) as well as the pivotal pro-fibrotic molecules IL-13, TGF-β and Smad3, while it increased the anti-fibrotic PPAR-γ. All these GED effects were nullified by co-administration of GW with GED. Furthermore, GED was able to normalize the expression levels of E-cadherin and β-catenin and upregulated GSK-3β, that are all known to be involved both in EMT and fibrosis. The DSS-induced intestinal fibrosis was improved by the new PPAR-γ modulator GED-0507-34 Levo through

Differential behavioral sensitivity to carbon dioxide (CO2) inhalation in rats

PubMed Central

Winter, Andrew; Ahlbrand, Rebecca; Naik, Devanshi; Sah, Renu

2017-01-01

Inhalation of carbon dioxide (CO2) is frequently employed as a biological challenge to evoke intense fear and anxiety. In individuals with panic disorder, CO2 reliably evokes panic attacks. Sensitivity to CO2 is highly heterogeneous among individuals, and although a genetic component is implicated, underlying mechanisms are not clear. Preclinical models that can simulate differential responsivity to CO2 are therefore relevant. In the current study we investigated CO2-evoked behavioral responses in four different rat strains: Sprague-Dawley (SD), Wistar (W), Long Evans (LE) and Wistar-Kyoto, (WK) rats. We also assessed tryptophan hydroxylase 2 (TPH-2)-positive serotonergic neurons in anxiety/panic regulatory subdivisions of the dorsal raphe nucleus (DR), as well as dopamine β hydroxylase (DβH)-positive noradrenergic neurons in the locus coeruleus, implicated in central CO2-chemosensitivity. Behavioral responsivity to CO2 inhalation varied between strains. CO2-evoked immobility was significantly higher in LE and WK rats as compared with W and SD cohorts. Differences were also observed in CO2-evoked rearing and grooming behaviors. Exposure to CO2 did not produce conditioned behavioral responses upon re-exposure to CO2 context in any strain. Reduced TPH-2 positive cell counts were observed specifically in the panic-regulatory dorsal raphe ventrolateral (DRVL)-ventrolateral periaqueductal grey (VLPAG) subdivision in CO2-sensitive strains. Conversely, DβH positive cell counts within the LC were significantly higher in CO2-sensitive strains. Collectively, our data provide evidence for strain dependent, differential CO2-sensitivity and potential differences in monoaminergic systems regulating panic and anxiety. Comparative studies between CO2-vulnerable and resistant strains may facilitate the mechanistic understanding of differential CO2-sensitivity in the development of panic and anxiety disorders. PMID:28087339

Drinking sucrose or saccharin enhances sensitivity of rats to quinpirole-induced yawning

PubMed Central

Serafine, Katherine M; Bentley, Todd A; Kilborn, Dylan J; Koek, Wouter; France, Charles P

2015-01-01

Diet can impact sensitivity of rats to some of the behavioral effects of drugs acting on dopamine systems. The current study tested whether continuous access to sucrose is necessary to increase yawning induced by the dopamine receptor agonist quinpirole, or if intermittent access is sufficient. These studies also tested whether sensitivity to quinpirole-induced yawning increases in rats drinking the non-caloric sweetener saccharin. Dose-response curves (0.0032–0.32 mg/kg) for quinpirole-induced yawning were determined once weekly in rats with free access to standard chow and either continuous access to water, 10% sucrose solution, or 0.1% saccharin solution, or intermittent access to sucrose or saccharin (i.e., 2 days per week with access to water on other days). Cumulative doses of quinpirole increased then decreased yawning, resulting in an inverted U-shaped dose-response curve. Continuous or intermittent access to sucrose enhanced sensitivity to quinpirole-induced yawning. Continuous, but not intermittent, access to saccharin also enhanced sensitivity to quinpirole-induced yawning. In all groups, pretreatment with the selective D3 receptor antagonist PG 01037 shifted the ascending limb of the quinpirole dose-response curve to the right, while pretreatment with the selective D2 receptor antagonist L-741626 shifted the descending limb to the right. These results suggest that even intermittent consumption of diets containing highly palatable substances (e.g. sucrose) alters sensitivity to drugs acting on dopamine systems in a manner that could be important in vulnerability to abuse drugs. PMID:26189020

Bile salts as semiochemicals in fish

USGS Publications Warehouse

Buchinger, Tyler J.; Li, Weiming; Johnson, Nicholas S.

2014-01-01

Bile salts are potent olfactory stimuli in fishes; however the biological functions driving such sensitivity remain poorly understood. We provide an integrative review of bile salts as semiochemicals in fish. First, we present characteristics of bile salt structure, metabolism, and function that are particularly relevant to chemical communication. Bile salts display a systematic pattern of structural variation across taxa, are efficiently synthesized, and are stable in the environment. Bile salts are released into the water via the intestine, urinary tract, or gills, and are highly water soluble. Second, we consider the potential role of bile salts as semiochemicals in the contexts of detecting nearby fish, foraging, assessing risk, migrating, and spawning. Lastly, we suggest future studies on bile salts as semiochemicals further characterize release into the environment, behavioral responses by receivers, and directly test the biological contexts underlying olfactory sensitivity.

A quantitative headspace-solid-phase microextraction-gas chromatography-flame ionization detector method to analyze short chain free fatty acids in rat feces.

PubMed

Fiorini, Dennis; Boarelli, Maria Chiara; Gabbianelli, Rosita; Ballini, Roberto; Pacetti, Deborah

2016-09-01

This study sought to develop and validate a quantitative method to analyze short chain free fatty acids (SCFAs) in rat feces by solid-phase microextraction and gas chromatography (SPME-GC) using the salt mixture ammonium sulfate and sodium dihydrogen phosphate as salting out agent. Conditioning and extraction time, linearity, limits of detection and quantification, repeatability, and recovery were evaluated. The proposed method allows quantification with improved sensitivity as compared with other methods exploiting SPME-GC. The method has been applied to analyze rat fecal samples, quantifying acetic, propionic, isobutyric, butyric, isopentanoic, pentanoic, and hexanoic acids. Copyright © 2016 Elsevier Inc. All rights reserved.

Hydrogen sulfide from a NaHS source attenuates dextran sulfate sodium (DSS)-induced inflammation via inhibiting nuclear factor-κB

PubMed Central

Chen, Xi; Liu, Xi-shuang

2016-01-01

This study investigated the alleviating effects of hydrogen sulfide (H2S), derived from sodium hydrosulfide (NaHS), on inflammation induced by dextran sulfate sodium (DSS) in both in vivo and in vitro models. We found that NaHS injection markedly decreased rectal bleeding, diarrhea, and histological injury in DSS-challenged mice. NaHS (20 μmol/L) reversed DSS-induced inhibition in cell viability in Caco-2 cells and alleviated pro-inflammation cytokine expression in vivo and in vitro, indicating an anti-inflammatory function for H2S. It was also found that H2S may regulate cytokine expression by inhibiting the nuclear factor-κB (NF-κB) signaling pathway. In conclusion, our results demonstrated that H2S alleviated DSS-induced inflammation in vivo and in vitro and that the signal mechanism might be associated with the NF-κB signaling pathway. PMID:26984841

“When the going gets tough, who keeps going?” Depletion sensitivity moderates the ego-depletion effect

PubMed Central

Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

2014-01-01

Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion. PMID:25009523

Dissipation of excess photosynthetic energy contributes to salinity tolerance: a comparative study of salt-tolerant Ricinus communis and salt-sensitive Jatropha curcas.

PubMed

Lima Neto, Milton C; Lobo, Ana K M; Martins, Marcio O; Fontenele, Adilton V; Silveira, Joaquim Albenisio G

2014-01-01

The relationships between salt tolerance and photosynthetic mechanisms of excess energy dissipation were assessed using two species that exhibit contrasting responses to salinity, Ricinus communis (tolerant) and Jatropha curcas (sensitive). The salt tolerance of R. communis was indicated by unchanged electrolyte leakage (cellular integrity) and dry weight in leaves, whereas these parameters were greatly affected in J. curcas. The leaf Na+ content was similar in both species. Photosynthesis was intensely decreased in both species, but the reduction was more pronounced in J. curcas. In this species biochemical limitations in photosynthesis were more prominent, as indicated by increased C(i) values and decreased Rubisco activity. Salinity decreased both the V(cmax) (in vivo Rubisco activity) and J(max) (maximum electron transport rate) more significantly in J. curcas. The higher tolerance in R. communis was positively associated with higher photorespiratory activity, nitrate assimilation and higher cyclic electron flow. The high activity of these alternative electron sinks in R. communis was closely associated with a more efficient photoprotection mechanism. In conclusion, salt tolerance in R. communis, compared with J. curcas, is related to higher electron partitioning from the photosynthetic electron transport chain to alternative sinks. Copyright © 2013 Elsevier GmbH. All rights reserved.

Cocaine sensitization does not alter SP effects on locomotion or excitatory synaptic transmission in the NAc of rats.

PubMed

Kombian, Samuel B; Ananthalakshmi, Kethireddy V V; Zidichouski, Jeffrey A; Saleh, Tarek M

2012-02-01

Substance P (SP) and cocaine employ similar mechanisms to modify excitatory synaptic transmission in the nucleus accumbens (NAc), a region implicated in substance abuse. Here we explored, using NAc slices, whether SP effects on these synaptic responses were altered in rats that have been sensitized to cocaine and whether SP could mimic cocaine in triggering increased locomotion in sensitized rats. Intraperitoneal (IP) injection of naïve rats with cocaine (15 mg/kg) caused increased locomotion by 408.5 ± 85.9% (n = 5) which further increased by 733.1 ± 157.8% (n = 5) following a week of cocaine sensitization. A similar challenge with 10 mg/kg of SP after cocaine sensitization did not produce significant changes in locomotion (170.6 ± 61.0%; n = 4). In contrast to cocaine, IP injection of rats with SP or SP(5-11) (10-100 mg/kg) with or without phosphoramidon did not elicit changes in locomotion. In electrophysiological studies, both cocaine and SP depressed evoked NMDA and non-NMDA receptor-mediated excitatory synaptic currents (EPSCs) in slices obtained from naïve rats. In slices derived from cocaine-sensitized rats, cocaine but not SP produced a more profound decrease in non-NMDA compared to NMDA responses. Similar to that in naïve rats, cocaine's effect on the EPSCs in these sensitized rats occluded those of SP. Thus, although SP and cocaine may employ similar mechanisms to depress EPSCs in the NAc, IP injection of SP does not mimic cocaine-induced hyperlocomotion indicating that not all of cocaine's effects are mimicked by SP. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.

Azilsartan treatment improves insulin sensitivity in obese spontaneously hypertensive Koletsky rats.

PubMed

Zhao, M; Li, Y; Wang, J; Ebihara, K; Rong, X; Hosoda, K; Tomita, T; Nakao, K

2011-12-01

Hypertension often coexists with insulin resistance. However, most metabolic effects of the antihypertensive agents have been investigated in nomotensive animals, in which different conclusions may arise. We investigated the metabolic effects of the new angiotensin II type 1 receptor blocker azilsartan using the obese Koletsky rats superimposed on the background of the spontaneously hypertensive rats. Male Koletsky rats were treated with azilsartan (2 mg/kg/day) over 3 weeks. Blood pressure was measured by tail-cuff. Blood biochemical and hormonal parameters were determined by enzymatic or ELISA methods. Gene expression was assessed by RT-PCR. In Koletsky rats, azilsartan treatment lowered blood pressure, basal plasma insulin concentration and the homeostasis model assessment of insulin resistance index, and inhibited over-increase of plasma glucose and insulin concentrations during oral glucose tolerance test. These effects were accompanied by decreases in both food intake and body weight (BW) increase. Although two treatments showed the same effect on BW gain, insulin sensitivity was higher after azilsartan treatment than pair-feeding. Azilsartan neither affected plasma concentrations of triglyceride and free fatty acids, nor increased adipose mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ and its target genes such as adiponectin, aP2. In addition, azilsartan downregulated 11β-hydroxysteroid dehydrogenase type 1 expression. These results show the insulin-sensitizing effect of azilsartan in obese Koletsky rats. This effect is independent of decreases in food intake and BW increase or of the activation of adipose PPARγ. Our findings indicate the possible usefulness of azilsartan in the treatment of metabolic syndrome. © 2011 Blackwell Publishing Ltd.

1H NMR spectroscopic analysis detects metabolic disturbances in rat urine on acute exposure to heavy metal tungsten alloy based metals salt.

PubMed

Tyagi, Ritu; Rana, Poonam; Gupta, Mamta; Bhatnagar, Deepak; Srivastava, Shatakshi; Roy, Raja; Khushu, Subash

2014-03-25

Heavy metal tungsten alloys (HMTAs) have been found to be safer alternatives for making military munitions. Recently, some studies demonstrating the toxic potential of HMTAs have raised concern over the safety issues, and further propose that HMTAs exposure may lead to physiological disturbances as well. To look for the systemic effect of acute toxicity of HMTA based metals salt, (1)H nuclear magnetic resonance ((1)H NMR) spectroscopic profiling of rat urine was carried out. Male Sprague Dawley rats were administered (intraperitoneal) low and high dose of mixture of HMTA based metals salt and NMR spectroscopy was carried out in urine samples collected at 8, 24, 72 and 120 h post dosing (p.d.). Serum biochemical parameters and liver histopathology were also conducted. The (1)H NMR spectra were analysed using multivariate analysis techniques to show the time- and dose-dependent biochemical variations in post HMTA based metals salt exposure. Urine metabolomic analysis showed changes associated with energy metabolism, amino acids, N-methyl nicotinamide, membrane and gut flora metabolites. Multivariate analysis showed maximum variation with best classification of control and treated groups at 24h p.d. At the end of the study, for the low dose group most of the changes at metabolite level reverted to control except for the energy metabolites; whereas, in the high dose group some of the changes still persisted. The observations were well correlated with histopathological and serum biochemical parameters. Further, metabolic pathway analysis clarified that amongst all the metabolic pathways analysed, tricarboxylic acid cycle was most affected at all the time points indicating a switchover in energy metabolism from aerobic to anaerobic. These results suggest that exposure of rats to acute doses of HMTA based metals salt disrupts physiological metabolism with moderate injury to the liver, which might indirectly result from heavy metals induced oxidative stress. Copyright �

Bone Density and High Salt Diets in a Space Flight Model

NASA Technical Reports Server (NTRS)

Arnaud, S. B.; Navidi, M.; Liang, M. T. C.; Wolinsky, I.

1999-01-01

High salt diets accelerate bone loss with aging in patients with postmenopausal osteoporosis except when calcium supplementation is provided. We have observed that the decrease in mineral content of growing femurs in juvenile rats, exposed to a space flight model which unloads the hind limbs , is substantially less in animals fed excess salt. To determine whether excess dietary salt has the same effect on the skeleton of the mature animal whose response to unloading is increased resorption and bone loss rather than impaired growth, we carried out a metabolic study in mature rats with hindlimbs unloaded by tailsuspension.

Chronic Blockade of Brain Endothelin Receptor Type-A (ETA) Reduces Blood Pressure and Prevents Catecholaminergic Overactivity in the Right Olfactory Bulb of DOCA-Salt Hypertensive Rats.

PubMed

Cassinotti, Luis R; Guil, María J; Schöller, Mercedes I; Navarro, Mónica P; Bianciotti, Liliana G; Vatta, Marcelo S

2018-02-27

Overactivity of the sympathetic nervous system and central endothelins (ETs) are involved in the development of hypertension. Besides the well-known brain structures involved in the regulation of blood pressure like the hypothalamus or locus coeruleus, evidence suggests that the olfactory bulb (OB) also modulates cardiovascular function. In the present study, we evaluated the interaction between the endothelinergic and catecholaminergic systems in the OB of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Following brain ET receptor type A (ET A ) blockade by BQ610 (selective antagonist), transcriptional, traductional, and post-traductional changes in tyrosine hydroxylase (TH) were assessed in the OB of normotensive and DOCA-salt hypertensive rats. Time course variations in systolic blood pressure and heart rate were also registered. Results showed that ET A blockade dose dependently reduced blood pressure in hypertensive rats, but it did not change heart rate. It also prevented the increase in TH activity and expression (mRNA and protein) in the right OB of hypertensive animals. However, ET A blockade did not affect hemodynamics or TH in normotensive animals. Present results support that brain ET A are not involved in blood pressure regulation in normal rats, but they significantly contribute to chronic blood pressure elevation in hypertensive animals. Changes in TH activity and expression were observed in the right but not in the left OB, supporting functional asymmetry, in line with previous studies regarding cardiovascular regulation. Present findings provide further evidence on the role of ETs in the regulation of catecholaminergic activity and the contribution of the right OB to DOCA-salt hypertension.

B-vitamin deficiency is protective against DSS-induced colitis in mice

PubMed Central

Benight, Nancy M.; Stoll, Barbara; Chacko, Shaji; da Silva, Vanessa R.; Marini, Juan C.; Gregory, Jesse F.; Stabler, Sally P.

2011-01-01

Vitamin deficiencies are common in patients with inflammatory bowel disease (IBD). Homocysteine (Hcys) is a thrombogenic amino acid produced from methionine (Met), and its increase in patients with IBD indicates a disruption of Met metabolism; however, the role of Hcys and Met metabolism in IBD is not well understood. We hypothesized that disrupted Met metabolism from a B-vitamin-deficient diet would exacerbate experimental colitis. Mice were fed a B6-B12-deficient or control diet for 2 wk and then treated with dextran sodium sulfate (DSS) to induce colitis. We monitored disease activity during DSS treatment and collected plasma and tissue for analysis of inflammatory tissue injury and Met metabolites. We also quantified Met cycle activity by measurements of in vivo Met kinetics using [1-13C-methyl-2H3]methionine infusion in similarly treated mice. Unexpectedly, we found that mice given the B-vitamin-deficient diet had improved clinical outcomes, including increased survival, weight maintenance, and reduced disease scores. We also found lower histological disease activity and proinflammatory gene expression (TNF-α and inducible nitric oxide synthase) in the colon in deficient-diet mice. Metabolomic analysis showed evidence that these effects were associated with deficient B6, as markers of B12 function were only mildly altered. In vivo methionine kinetics corroborated these results, showing that the deficient diet suppressed transsulfuration but increased remethylation. Our findings suggest that disrupted Met metabolism attributable to B6 deficiency reduces the inflammatory response and disease activity in DSS-challenged mice. These results warrant further human clinical studies to determine whether B6 deficiency and elevated Hcys in patients with IBD contribute to disease pathobiology. PMID:21596995

Splanchnic sympathetic nerves in the development of mild DOCA-salt hypertension

PubMed Central

Kandlikar, Sachin S.

2011-01-01

We previously reported that mild deoxycorticosterone acetate (DOCA)-salt hypertension develops in the absence of generalized sympathoexcitation. However, sympathetic nervous system activity (SNA) is regionally heterogeneous, so we began to investigate the role of sympathetic nerves to specific regions. Our first study on that possibility revealed no contribution of renal nerves to hypertension development. The splanchnic sympathetic nerves are implicated in blood pressure (BP) regulation because splanchnic denervation effectively lowers BP in human hypertension. Here we tested the hypothesis that splanchnic SNA contributes to the development of mild DOCA-salt hypertension. Splanchnic denervation was achieved by celiac ganglionectomy (CGX) in one group of rats while another group underwent sham surgery (SHAM-GX). After DOCA treatment (50 mg/kg) in rats with both kidneys intact, CGX rats exhibited a significantly attenuated increase in BP compared with SHAM-GX rats (15.6 ± 2.2 vs. 25.6 ± 2.2 mmHg, day 28 after DOCA treatment). In other rats, whole body norepinephrine (NE) spillover, measured to determine if CGX attenuated hypertension development by reducing global SNA, was not found to be different between SHAM-GX and CGX rats. In a third group, nonhepatic splanchnic NE spillover was measured as an index of splanchnic SNA, but this was not different between SHAM (non-DOCA-treated) and DOCA rats during hypertension development. In a final group, CGX effectively abolished nonhepatic splanchnic NE spillover. These data suggest that an intact splanchnic innervation is necessary for mild DOCA-salt hypertension development but not increased splanchnic SNA or NE release. Increased splanchnic vascular reactivity to NE during DOCA-salt treatment is one possible explanation. PMID:21890693

Acid/Salt/pH Gradient Improved Resolution and Sensitivity in Proteomics Study Using 2D SCX-RP LC-MS.

PubMed

Zhu, Ming-Zhi; Li, Na; Wang, Yi-Tong; Liu, Ning; Guo, Ming-Quan; Sun, Bao-Qing; Zhou, Hua; Liu, Liang; Wu, Jian-Lin

2017-09-01

The usage of strong cation exchange (SCX) chromatography in proteomics is limited by its poor resolution and nonspecific hydrophobic interactions with peptides, which lead to peptide overlap across fractions and change of peptide retention, respectively. The application of high concentration of salt (up to 1000 mM) in SCX also restricted its use in online 2D SCX-RP LC. In the present research, we first exploited the chromatographic ability of online 2D SCX-RP LC by combination of acid, salt, and pH gradient, three relatively independent modes of eluting peptides from SCX column. 50% ACN was added to elution buffer for eliminating hydrophobic interactions between SCX matrix and peptides, and the concentration of volatile salt was reduced to 50 mM. Acid/salt/pH gradient showed superior resolution and sensitivity as well as uniform distribution across fractions, consequently leading to significant improvements in peptide and protein identification. 112 191 unique peptides and 7373 proteins were identified by acid/salt/pH fractionation, while 69 870 unique peptides and 4536 proteins were identified by salt elution, that is, 62.5 and 60.6% more proteins and unique peptides, respectively, identified by the former. Fraction overlap was also significantly minimized by acid/salt/pH approach. Furthermore, acid/salt/pH elution showed more identification for acidic peptides and hydrophilic peptides.

Effects of prolonged abstinence from METH on the hippocampal BDNF levels, neuronal numbers and apoptosis in methamphetamine-sensitized rats.

PubMed

Hajheidari, Samira; Sameni, Hamid Reza; Bandegi, Ahmad Reza; Miladi-Gorji, Hossein

2017-04-03

Methamphetamine (METH) use is associated with neuronal damage in various regions of brain, while effects of prolonged abstinence on METH-induced damage are not quite clear. This study evaluated serum and hippocampal BDNF levels, neuronal numbers and apoptosis in METH-sensitized and abstinent rats. Rats were sensitized to METH (2mg/kg, daily/18 days, s.c.). All rats were evaluated for neuron counting, the TUNEL test and serum and hippocampal BDNF levels after 30 days of forced abstinence from METH. The results showed that increased BDNF levels in the hippocampus and serum of METH-sensitized rats returned to control level after 30 days of abstinence. The number of neurons in the DG and CA1 of hippocampus and also, the total hippocampal perimeter and area in METH-sensitized rats were significantly lower than the saline rats. While, the number of neurons was not significantly increased in the hippocampus after prolonged abstinence from METH. Also, METH-sensitized rats showed a significant increase in TUNEL-positive cells, whereas METH-abstinent rats showed a slight but significant decrease in TUNEL-positive cells in the DG and CA3 of hippocampus. These results suggest that despite the reduction in BDNF levels, reducing the number of neurons, perimeter and area of the hippocampus were stable after abstinence. Thus, the degenerative effects of METH have been sustained even after prolonged abstinence in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

Bilirubin prevents acute DSS-induced colitis by inhibiting leukocyte infiltration and suppressing upregulation of inducible nitric oxide synthase

PubMed Central

Vogel, Megan E.; Kindel, Tammy L.; Smith, Darcey L. H.; Idelman, Gila; Avissar, Uri; Kakarlapudi, Ganesh; Masnovi, Michelle E.

2015-01-01

Bilirubin is thought to exert anti-inflammatory effects by inhibiting vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration and by suppressing the expression of inducible nitric oxide synthase (iNOS). As VCAM-1 and iNOS are important mediators of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. Male C57BL/6 mice were administered 2.5% DSS in the drinking water for 7 days, while simultaneously receiving intraperitoneal injections of bilirubin (30 mg/kg) or potassium phosphate vehicle. Disease activity was monitored, peripheral blood counts and serum nitrate levels were determined, and intestinal specimens were analyzed for histological injury, leukocyte infiltration, and iNOS expression. The effect of bilirubin on IL-5 production by HSB-2 cells and on Jurkat cell transendothelial migration also was determined. DSS-treated mice that simultaneously received bilirubin lost less body weight, had lower serum nitrate levels, and exhibited reduced disease severity than vehicle-treated animals. Concordantly, histopathological analyses revealed that bilirubin-treated mice manifested significantly less colonic injury, including reduced infiltration of eosinophils, lymphocytes, and monocytes, and diminished iNOS expression. Bilirubin administration also was associated with decreased eosinophil and monocyte infiltration into the small intestine, with a corresponding increase in peripheral blood eosinophilia. Bilirubin prevented Jurkat migration but did not alter IL-5 production. In conclusion, bilirubin prevents DSS-induced colitis by inhibiting the migration of leukocytes across the vascular endothelium and by suppressing iNOS expression. PMID:26381705

Bilirubin prevents acute DSS-induced colitis by inhibiting leukocyte infiltration and suppressing upregulation of inducible nitric oxide synthase.

PubMed

Zucker, Stephen D; Vogel, Megan E; Kindel, Tammy L; Smith, Darcey L H; Idelman, Gila; Avissar, Uri; Kakarlapudi, Ganesh; Masnovi, Michelle E

2015-11-15

Bilirubin is thought to exert anti-inflammatory effects by inhibiting vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration and by suppressing the expression of inducible nitric oxide synthase (iNOS). As VCAM-1 and iNOS are important mediators of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. Male C57BL/6 mice were administered 2.5% DSS in the drinking water for 7 days, while simultaneously receiving intraperitoneal injections of bilirubin (30 mg/kg) or potassium phosphate vehicle. Disease activity was monitored, peripheral blood counts and serum nitrate levels were determined, and intestinal specimens were analyzed for histological injury, leukocyte infiltration, and iNOS expression. The effect of bilirubin on IL-5 production by HSB-2 cells and on Jurkat cell transendothelial migration also was determined. DSS-treated mice that simultaneously received bilirubin lost less body weight, had lower serum nitrate levels, and exhibited reduced disease severity than vehicle-treated animals. Concordantly, histopathological analyses revealed that bilirubin-treated mice manifested significantly less colonic injury, including reduced infiltration of eosinophils, lymphocytes, and monocytes, and diminished iNOS expression. Bilirubin administration also was associated with decreased eosinophil and monocyte infiltration into the small intestine, with a corresponding increase in peripheral blood eosinophilia. Bilirubin prevented Jurkat migration but did not alter IL-5 production. In conclusion, bilirubin prevents DSS-induced colitis by inhibiting the migration of leukocytes across the vascular endothelium and by suppressing iNOS expression. Copyright © 2015 the American Physiological Society.

Hippocampal GABAA Receptor and Pain Sensitivity during Estrous Cycle in the Rat

PubMed Central

Taherianfard, Mahnaz; Mosavi, Mahnaz

2011-01-01

Background: Estradiol and progesterone as well as hippocampal GABAA receptors are believed to play a role in the modulation of pain. The aim of present study was to investigate the effect of intrahippocampal injections of GABAA receptor agonist (muscimol) and GABAA receptor antagonist (picrotoxin) on pain sensitivity during estrous cycle. Methods: Pain sensitivity was evaluated in rats by formalin test during all stages of estrous cycle. Animals were divided into five groups including; 1- control (intact animal); 2- sham 1 receiving 0.75 µl artificial cerebrospinal fluids (ACSF); 3- sham 2 receiving 0.75 µl alcoholic ACSF; 4- experimental 1 receiving 250 or 500 µg/rat of muscimol in 0.75 µl vehicle, and 5- experimental 2 receiving 20 or 30 µg/rat picrotoxin in 0.75 µl vehicle. Data were analyzed by Kruskal-Wallis followed by Tucky's test for pairwise comparisons using a P value of ≤0.50 for statistical significance. Results: Muscimol significantly (P<0.05) decreased pain sensitivity in all stages of estrous cycle, and the analgesic effect was higher during proestrus and estrus stages of estrous cycle than that during metestrus and diestrus stages. Picrotoxin significantly (P<0.05) increased pain sensitivity in all stages of estrous cycle, and such a hyperalgesic effect was lower during proestrus and estrus stages of estrous cycle than that during metestrus and diestrus stages. Conclusion: The findings of the present study indicate that the role of hippocampal GABAA receptor in the control of the pain sensitivity can be modulated by variation in gonadal steroids during different stages of the estrous cycle. PMID:23115414

In vitro and in vivo evaluation of sanguinarine liposomes prepared by a remote loading method with three different ammonium salts.

PubMed