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Therapeutic Research
- Authors: Haruki Sasaki1, et al.
Abstract
Hypertension is a major risk factor for the development of heart failue. Therefore, anti‒hypertensive therapies are required to have not only the effect of lowering blood pressure, but also the cardioprotective effect. Recent studies by us and others suggest that bradykinin(BK)B1 receptor(B1R)is induced in a varaiety of tissues in some pathological conditions including hypertensive cardiac remodeling and exerts organ protective effects. Hence, pharmacological enhancement of B1R will be a novel strategy for hypertensive organ damages. A recent report showed that B1R was upregulated by an angiotensin type 1 receptor(AT1R)blocker(ARB)in the experimental myocardial infarcted heart and had beneficial effects against the cardiac remodeling. In this study, we examined the effects of valsartan, an ARB, on the expression of B1R and its role in hypertensive cardiac remodeling. Twelve‒week‒old stroke‒prone spontaneously hypertensive rats(SHR‒SPs)were assigned to the treatment with saline, hydralazine, or valsartan for four weeks. Valsartan increased the expression of cardiac B1R mRNA compared to the control treatment, while hydralazine did not alter it at all. Then we assesed the role of upregulated B1R during ARB treatment with a B1R antagonist. Rats were assigned to treatment with saline, hydralazine, valsartan, or valsartan plus B1R antagonist. Valsartan significantly reduced systolic blood pressure, while the addition of B1R antagonist on top of valsartan did not alter systolic blood pressure. Hydralazine further reduced systolic blood pressure than valsartan or valsartan plus B1R antagonist. Left ventricule weight to body weight ratio, cardiomyocyte size, and interstitial fibrosis were significantly reduced in the rats treated with valsartan, and these beneficial effects of valsartan were partially reversed by co‒treatment with B1R antagonist. The expression of transforming growth factor(TGF)‒β1 in rats treated with valsartan was significantly reduced, and the reduced expression was partially reversed by the co‒treatment with B1R antagonist. These results indicate that B1R is upregulated by ARB and may have cardioprotective effects in severe hypertension.
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