Valproic acid prevents the deregulation of lipid metabolism and renal renin–angiotensin system in l-NAME induced nitric oxide deficient hypertensive rats

The development of malignant hypertension was studied in stroke-prone spontaneously hypertensive rats (SHR) kept on 1% NaCl as drinking water. Along with salt-loading, blood pressure gradually increased and reached a severe hypertensive level (greater than 230 mmHg), which was followed by increases in urinary protein (greater than 100 (mg/250 g body wt)/day) and plasma renin concentration (PRC, from 18.9 +/- 0.1 to 51.2 +/- 19.4 (ng/ml)/h, mean +/- SD). At this stage, renal small arteries and arterioles showed severe sclerosis and fibrinoid necrosis. Stroke was observed within a week after the onset of these renal abnormalities. The dose of exogenous angiotensin II (AII) producing 30 mmHg rise in blood pressure increased with the elevation of PRC, from 22 +/- 12 to 75 +/- 36 ng/kg, which was comparable to that in rats on water. The fall of blood pressure due to an AII inhibitor, [1-sarcosine, 8-alanine]AII (10(microgram/kg)/min for 40 min) became more prominent with the increase in PRC in salt-loaded rats, but was not detected in rats on water. These findings suggest that the activation of renin-angiotensin system participates in malignant hypertension of salt-loaded stroke-prone SHR rats that show stroke signs, proteinuria, hyperreninemia, and renovascular changes.

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Hydrogen peroxide and nitric oxide induce anticontractile effect of perivascular adipose tissue via renin angiotensin system activation

Nitric Oxide ◽

10.1016/j.niox.2018.12.011 ◽

2019 ◽

Vol 84 ◽

pp. 50-59 ◽

Cited By ~ 5

Author(s):

Natália Nóbrega ◽

Natália Ferreira Araújo ◽

Daniela Reis ◽

Larissa Moreira Facine ◽

Claudiane Aparecida S. Miranda ◽

...

Keyword(s):

Nitric Oxide ◽

Hydrogen Peroxide ◽

Adipose Tissue ◽

Renin Angiotensin System ◽

Perivascular Adipose Tissue ◽

Angiotensin System ◽

Renin Angiotensin ◽

System Activation

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The role of the renin-angiotensin system and oxidative stress in spontaneously hypertensive rat mesenteric collateral growth impairment

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01296.2006 ◽

2007 ◽

Vol 292 (5) ◽

pp. H2523-H2531 ◽

Cited By ~ 21

Author(s):

Steven J. Miller ◽

Laura E. Norton ◽

Michael P. Murphy ◽

Michael C. Dalsing ◽

Joseph L. Unthank

Keyword(s):

Renin Angiotensin System ◽

Ang Ii ◽

Hypertensive Rats ◽

Angiotensin System ◽

Spontaneously Hypertensive ◽

Renin Angiotensin ◽

Growth Impairment ◽

Collateral Growth ◽

Collateral Artery

Recent clinical and animal studies have shown that collateral artery growth is impaired in the presence of vascular risk factors, including hypertension. Available evidence suggests that angiotensin-converting enzyme inhibitors (ACEI) promote collateral growth in both hypertensive humans and animals; however, the specific mechanisms are not established. This study evaluated the hypothesis that collateral growth impairment in hypertension is mediated by excess superoxide produced by NAD(P)H oxidase in response to stimulation of the ANG II type 1 receptor. After ileal artery ligation, mesenteric collateral growth did not occur in untreated, young, spontaneously hypertensive rats. Significant luminal expansion occurred in collaterals of spontaneously hypertensive rats treated with the superoxide dismutase mimetic tempol, the NAD(P)H oxidase inhibitor apocynin, and the ACEI captopril, but not ANG II type 1 (losartan) or type 2 (PD-123319) receptor blockers. The ACEI enalapril produced equivalent reduction of arterial pressure as captopril but did not promote luminal expansion. This suggests the effects of captopril on collateral growth might result from its antioxidant properties. RT-PCR demonstrated that ANG II type 1 receptor and angiotensinogen expression was reduced in collaterals of untreated rats. This local suppression of the renin angiotensin system provides a potential explanation for the lack of effect of enalapril and losartan on collateral growth. The results demonstrate the capability of antioxidant therapies, including captopril, to reverse impaired collateral artery growth and the novel finding that components of the local renin angiotensin system are naturally suppressed in collaterals.

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