Roles of Nitric Oxide and Oxidative Stress in the Regulation of Blood Pressure and Renal Function in Prehypertensive Ren-2 Transgenic Rats

2005 ◽  
Vol 28 (2) ◽  
pp. 117-126 ◽  
Author(s):  
Ivana Vaněčková ◽  
Herbert J. Kramer ◽  
Jana Novotná ◽  
Ludmila Kazdová ◽  
Martin Opočenský ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Blood Pressure ◽  
Renal Function ◽  
Transgenic Rats ◽  
Regulation Of Blood Pressure ◽  
And Oxidative Stress

Abstract 16443: Effects of Dietary Salt Intakes on Blood Pressure, Renal Function and Oxidative Stress in Rats Treated With Candesartan

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Gangyi Zhu ◽  
Yanting Yu ◽  
Xiaoyan Wang
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Renal Function ◽  
Kidney Diseases ◽  
Sprague Dawley ◽  
Dietary Salt ◽  
Salt Restriction ◽  
Low Salt ◽  
Receptor Blockers ◽  
And Oxidative Stress

Candesartan is one of angiotensin II type1 receptor blockers(ARB) and commonly used as first-line antihypertensive treatment. Low salt diet is often recommended by clinicians to the patients with hypertension and kidney diseases. However,it is not clear whether salt restriction is beneficial to the patients taking ARB. In order to explore this problem, the impacts of different salt diets on blood pressure (BP),renal function and oxidative stress were determined in 2-3 months old male Sprague Dawley rats treated with candesartan. The rats were randomly divided into 4 groups fed agar-gelled food rationally with NaCl content at 0.01%, 0.8%, 2% and 4% respectively(4-7 rats/group) while all rats were intraperitoneally injected with candesartan at 1mg / kg / day for 7 days. SBP started to decline on day 2 in all except 4% NaCl groups relative to day 0 (recorded 5-6 hrs before the first injection). On day 6, systolic BP (mmHg, tail-cuff, Softron,BP-98A) was lower in 0.8% (103.7+2.3) & 0.01% (101.6+3) groups than 2% (113.5+4.1) & 4% (129.9+4.6) groups (one way ANOVA,LSD test, P<0.05) and correlated positively with food NaCl intakes (R 2 =0.9832). DBP was changed in a similar pattern as SBP. Serum creatinine (μmol/L) was higher in 0.01% group (225+39) than groups of 0.8% (1328+350), 2% (2095+242) and 4% (1576+703) while creatinine clearance (ml/day) was lower in 0.01% group (69.3+9) than groups of 0.8% (43.7+9), 2%(27.7+2) and 4%(29+0.6). In order to determine whether oxidative stress plays any role in the BP regulation and renal function maintenance, we also checked renal protein expression of ROS components. Relative to 0.8% group, renal NOXs were not altered in 0.01% group while NOX1 (145+18,% of 0.8% group), NOX2 (240+54) and NOX4 (197+41) was higher in 2% group than other groups. Mn-SOD (77+7.8), not Cu-Zn SOD, was decreased while HO1 (170+16), not HO2, was increased in 0.01% group. Renal abundance of nitrotyrosine was lower in 0.01% than other groups indicating a decreased oxidative stress, possibly caused by increase in HO1. We concluded that salt restriction with candesartan is beneficial to antihypertensive effect of AT1R blockade but disadvantage to maintenance of renal function. Thus, cautions to choice of low salt intakes are necessary when taking ARB agents.

scholarly journals Rosiglitazone Decreases Blood Pressure in Female Dahl Rats: Role of Nitric Oxide and Oxidative Stress

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Julio C. Sartori‐Valinotti ◽  
Michael J. Ryan ◽  
Huimin Zhang ◽  
Jane F. Reckelhoff
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Blood Pressure ◽  
And Oxidative Stress

scholarly journals Macrophage Mineralocorticoid Receptor Signaling Plays a Key Role in Aldosterone-Independent Cardiac Fibrosis

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3416-3425 ◽  
Author(s):  
Laura A. Bienvenu ◽  
James Morgan ◽  
Amanda J. Rickard ◽  
Greg H. Tesch ◽  
Greg A. Cranston ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Mineralocorticoid Receptor ◽  
Cardiac Fibrosis ◽  
Plasma Aldosterone ◽  
Mrna Levels ◽  
Wild Type ◽  
And Oxidative Stress

Mineralocorticoid receptor (MR) activation promotes the development of cardiac fibrosis and heart failure. Clinical evidence demonstrates that MR antagonism is protective even when plasma aldosterone levels are not increased. We hypothesize that MR activation in macrophages drives the profibrotic phenotype in the heart even when aldosterone levels are not elevated. The aim of the present study was to establish the role of macrophage MR signaling in mediating cardiac tissue remodeling caused by nitric oxide (NO) deficiency, a mineralocorticoid-independent insult. Male wild-type (MRflox/flox) and macrophage MR-knockout (MRflox/flox/LysMCre/+; mac-MRKO) mice were uninephrectomized, maintained on 0.9% NaCl drinking solution, with either vehicle (control) or the nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME; 150 mg/kg/d) for 8 wk. NO deficiency increased systolic blood pressure at 4 wk in wild-type l-NAME/salt-treated mice compared with all other groups. At 8 wk, systolic blood pressure was increased above control in both l-NAME/salt treated wild-type and mac-MRKO mice by approximately 28 mm Hg by l-NAME/salt. Recruitment of macrophages was increased 2- to 3-fold in both l-NAME/salt treated wild-type and mac-MRKO. Inducible NOS positive macrophage infiltration and TNFα mRNA expression was greater in wild-type l-NAME/salt-treated mice compared with mac-MRKO, demonstrating that loss of MR reduces M1 phenotype. mRNA levels for markers of vascular inflammation and oxidative stress (NADPH oxidase 2, p22phox, intercellular adhesion molecule-1, G protein-coupled chemokine receptor 5) were similar in treated wild-type and mac-MRKO mice compared with control groups. In contrast, l-NAME/salt treatment increased interstitial collagen deposition in wild-type by about 33% but not in mac-MRKO mice. mRNA levels for connective tissue growth factor and collagen III were also increased above control treatment in wild-type (1.931 ± 0.215 vs. 1 ± 0.073) but not mac-MRKO mice (1.403 ± 0.150 vs. 1.286 ± 0.255). These data demonstrate that macrophage MR are necessary for the translation of inflammation and oxidative stress into interstitial and perivascular fibrosis after NO deficiency, even when plasma aldosterone is not elevated.

scholarly journals The effect of N-acetylcysteine on renal function, nitric oxide, and oxidative stress after angiography

2003 ◽  
Vol 64 (6) ◽  
pp. 2182-2187 ◽  
Author(s):  
SHAI Efrati ◽  
Victor Dishy ◽  
Michael Averbukh ◽  
Alex Blatt ◽  
Ricardo Krakover ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Renal Function ◽  
And Oxidative Stress

Adenosine A1-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment

2011 ◽  
Vol 301 (6) ◽  
pp. R1669-R1681 ◽  
Author(s):  
Xiang Gao ◽  
Andreas Patzak ◽  
Mauricio Sendeski ◽  
Peter G. Scheffer ◽  
Tom Teerlink ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Blood Pressure ◽  
Tubuloglomerular Feedback ◽  
Oxidative Stress Marker ◽  
No Production ◽  
Ang Ii ◽  
Simultaneous Treatment ◽  
Blood Pressure Responses ◽  
And Oxidative Stress

Adenosine mediates tubuloglomerular feedback responses via activation of A1-receptors on the renal afferent arteriole. Increased preglomerular reactivity, due to reduced nitric oxide (NO) production or increased levels of ANG II and reactive oxygen species (ROS), has been linked to hypertension. Using A1-receptor knockout (A1−/−) and wild-type (A1+/+) mice we investigated the hypothesis that A1-receptors modulate arteriolar and blood pressure responses during NO synthase (NOS) inhibition or ANG II treatment. Blood pressure and renal afferent arteriolar responses were measured in nontreated mice and in mice with prolonged Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME) or ANG II treatment. The hypertensive responses to l-NAME and ANG II were clearly attenuated in A1−/− mice. Arteriolar contractions to l-NAME (10−4 mol/l; 15 min) and cumulative ANG II application (10−12 to 10−6 mol/l) were lower in A1−/− mice. Simultaneous treatment with tempol (10−4 mol/l; 15 min) attenuated arteriolar responses in A1+/+ but not in A1−/− mice, suggesting differences in ROS formation. Chronic treatment with l-NAME or ANG II did not alter arteriolar responses in A1−/− mice, but enhanced maximal contractions in A1+/+ mice. In addition, chronic treatments were associated with higher plasma levels of dimethylarginines (asymmetrical and symmetrical) and oxidative stress marker malondialdehyde in A1+/+ mice, and gene expression analysis showed reduced upregulation of NOS-isoforms and greater upregulation of NADPH oxidases. In conclusion, adenosine A1-receptors enhance preglomerular responses during NO inhibition and ANG II treatment. Interruption of A1-receptor signaling blunts l-NAME and ANG II-induced hypertension and oxidative stress and is linked to reduced responsiveness of afferent arterioles.

scholarly journals Administration of Telmisartan Reduced Systolic Blood Pressure and Oxidative Stress Probably Through the Activation of PI3K/Akt/eNOS Pathway and NO Release in Spontaneously Hypertensive Rats

2013 ◽  
pp. 351-359 ◽  
Author(s):  
L. XU ◽  
Y. LIU
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Spontaneously Hypertensive Rats ◽  
Angiotensin Ii Receptor ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
No Release ◽  
And Oxidative Stress

We investigated the effects of telmisartan, the blocker of angiotensin II receptor 1, on the regulation of systolic blood pressure (SBP) and oxidative stress through endothelial nitric oxide (NO) release in spontaneously hypertensive rats (SHRs). SHRs randomly received placebo, oral feeding of telmisartan (5 mg/kg or 10 mg/kg) every day and Wistar-Kyoto rats (WKYs) served as normotensive control. The SBP of rat was measured before and weekly thereafter. After a total of 8-week treatment, rats were killed for experimental measurements. Parameters that subject to measurements in isolated aorta endothelial cells include: NO concentration, protein expression levels of angiotensin II receptor 1, nitrotyrosine, 8-isoprostane, SOD, PI3K, Akt, AMPK and eNOS. In addition, L-NMMA, a general inhibitor of nitric oxide synthase, was also applied to test the inhibition of NO concentration. We found that SBPs were significantly lower in telmisartan therapy group than in placebo treated hypertensive rats and WKYs (p<0.05). The NO concentration was significantly higher in telmisartan-treated group with increased activity of the PI3K/Akt pathway and activated eNOS signaling. Blockade of Akt activity reversed such effects. Activation of AMPK also contributed to the phosphorylation of eNOS. L-NMMA treatment reduced less NO concentration in SHR rats than the telmisartan co-treated groups. Oxidative stress in SHRs was also attenuated by telmisartan administration, shown by reduced formation of nitrotyrosine, 8-isoprostane, and recovered SOD protein level. Telmisartan enhanced NO release by activating the PI3K/Akt system, AMPK phosphorylation and eNOS expression, which attenuated the blood pressure and oxidative stress in SHRs.

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