Temporary treatment with AT1 receptor blocker, valsartan, from early stage of hypertension prevented vascular remodeling.

Abstract:

BACKGROUND:The present study examined the inhibitory action of temporary treatment with an angiotensin type 1 (AT(1)) receptor blocker (ARB) on vascular remodeling using hypertensive mice with overexpression of the human renin (hRN) and angiotensinogen (hANG) genes. METHODS:hRN/hANG transgenic mice (hRN/hANG-Tg) were treated with an ARB, valsartan, from 4 weeks of age. In some mice, valsartan treatment was stopped at 8 weeks of age (temporary treatment). Inflammatory vascular injury was induced by polyethylene-cuff placement around the femoral artery at the age of 10 weeks. RESULTS:Compared with wild-type (WT) mice, hRN/hANG-Tg showed higher blood pressure (BP) and enhancement of oxidative stress and medial thickening even before cuff placement. Inflammatory vascular remodeling and oxidative stress after cuff placement were further enhanced in hRN/hANG-Tg. Temporary treatment with valsartan continuously lowered BP even after cessation of administration, and inhibited these changes. In contrast, administration of hydralazine lowered BP to a similar level to that with valsartan, but did not inhibit medial thickening and inflammatory vascular remodeling. In contrast to the valsartan treatment, BP immediately increased to the untreated level after cessation of hydralazine. CONCLUSIONS:These results indicate that temporary ARB treatment leads to prolonged effect of BP lowering and prevents vascular remodeling in hypertensive mice induced by activation of the human renin-angiotensin system. The inhibitory action of valsartan is not due to the BP lowering but is at least in part due to a decrease in oxidative stress and inflammation.

journal_name

Am J Hypertens

authors

Inaba S,Iwai M,Furuno M,Kanno H,Senba I,Okayama H,Mogi M,Higaki J,Horiuchi M

doi

10.1038/ajh.2011.6

subject

Has Abstract

pub_date

2011-05-01 00:00:00

pages

550-6

issue

5

eissn

0895-7061

issn

1941-7225

pii

ajh20116

journal_volume

24

pub_type

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