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Cardioprotective effect of angiotensin II type 1 receptor antagonist associated with bradykinin-endothelial nitric oxide synthase and oxidative stress in Dahl salt-sensitive hypertensive rats.

Abstract：

OBJECTIVES:The interactions between eNOS or oxidative stress and bradykinin under long-term treatment of angiotensin II type 1 receptor antagonists (ATRA) remain unknown. To elucidate the molecular mechanisms of the cardioprotective effect of ATRA, we evaluated whether valsartan affects the bradykinin-eNOS and nicotinamide adenine dinucleotide (NAD(P)H) oxidase pathway. METHODS:After 5 weeks of feeding an 8% NaCl diet to 6-week-old Dahl salt-sensitive hypertensive (DS) rats, a distinct stage of concentric left ventricular hypertrophy (LVH) was noted. Six-week-old DS rats were treated with one of the following drug combinations for 5 weeks until the onset of LVH: vehicle; bradykinin B2 receptor antagonist FR172,357 alone; high-dose hydralazine; low-dose hydralazine; high-dose valsartan; low-dose valsartan; high and low-dose valsartan plus FR172,357. Age-matched Dahl salt-resistant rats fed the same diet served as controls. RESULTS:eNOS expression and activity, which was decreased in hypertrophy, was increased by high or low-dose valsartan, but not by high and low-dose valsartan plus FR172,357 or FR172,357 alone or high and low-dose hydralazine. The increased expression of NAD(P)H oxidase p22phox, p47phox, p67phox, and gp91phox in DS rats was suppressed by high or low-dose valsartan, but not by high or low-dose valsartan plus FR172,357 or FR172,357 alone or high and low-dose hydralazine. Valsartan effectively inhibited vascular lesion formation and suppressed the expression of transforming growth factor-beta1, connective tissue growth factor, and type I collagen, but not valsartan plus FR172,357 or FR172,357 alone or high and low-dose hydralazine. CONCLUSION:These findings suggest that valsartan may have cardioprotective effects in this model, partly associated with the bradykinin-eNOS and oxidative stress pathway.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Yoshida K,Kobayashi N,Ohno T,Fukushima H,Matsuoka H

doi

10.1097/HJH.0b013e32814db89f

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

1633-42

issue

eissn

0263-6352

issn

1473-5598

pii

00004872-200708000-00017

journal_volume

pub_type

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Cardioprotective effect of angiotensin II type 1 receptor antagonist associated with bradykinin-endothelial nitric oxide synthase and oxidative stress in Dahl salt-sensitive hypertensive rats.