Cardiovascular effects of valsartan and amlodipine in salt-loaded spontaneously hypertensive rats

Abstract

Salt sensitivity defined as increase in blood pressure in response to high dietary salt intake, is an independent risk factor for cardiovascular disease and mortality [1]. Even in the absence of prominent elevations of blood pressure after salt-loading, salt sensitivity may be revealed by structural and functional injury to target organs such as vasculature, heart and kidneys [2-4]. Available data strongly suggest that salt overload exerts these adverse effects through pressure independent mechanisms [5, 6]. Moreover, recent results also suggest that the renin– angiotensin system (RAS) is involved in mediating the adverse effects of salt, since RAS blockade prevented or ameliorated salt-induced cardiovascular and renal injury [5, 7]. Treatment strategies give advantage to hypertension therapies that can provide benefits beyond blood pressure lowering. Angiotensin receptor blockers (ARBs) are often supplemented with calcium channel blockers (CCBs) for treatment of hypertension [8]. Valsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in the vascular smooth muscle. Amlodipine inhibits calcium ion influx across cell membranes, with a greater effect on vascular smooth muscle cells. This causes vasodilation and a reduction in peripheral vascular resistance, thus lowering blood pressure. The objective of this study was to evaluate protective effects of 12-week treatment with valsartan and amlodipine given as monotherapy and as a combination on the heart and large blood vessels histopathology in salt loaded SHR rats.