ANGIOTENSIN-(1-7) AND NITRIC-OXIDE INTERACTION IN RENOVASCULAR HYPERTENSION

New studies suggest that vasodilator systems may play an important rol e in restraining the rise in peripheral vascular resistance associated with the evolution of arterial hypertension. We characterized in cons cious dogs the hemodynamic and hormonal effects of 4 weeks of feeding either the nitric oxide synthase inhibitor N-omega-nitro-L-arginine (3 mg . kg-(1) . d(-1)) or the nitric oxide precursor L-arginine (0.3 mg . k(-1) . d(-1)) during the evolution of two-kidney, one clip hyperte nsion. Inhibition of nitric oxide production elicited a form of hypert ension more severe than that produced in placebo-fed two-kidney, one c lip dogs. The higher levels of blood pressure were. accompanied by low er levels of plasma renin activity and lower angiotensin II concentrat ions. During the chronic phase of renovascular hypertension, the fall in blood pressure produced by acute systemic injections of lisinopril or losartan was significantly reduced in dogs given the nitric oxide i nhibitor. In contrast, chronic administration of L-arginine had no eff ect on the magnitude of hypertension or on the increases in renin acti vity and hyperangiotensinemia associated with the evolution of renal h ypertension. Likewise, the fall in blood pressure produced by pharmaco logical blockade of angiotensin II was not different from that recorde d in untreated renal hypertensive dogs. The vasodilator component of t he blood pressure response due to intravenous injections of angiotensi n-(1-7) (1 to 100 nmol/kg) was augmented in both untreated and L-argin ine-treated two-kidney, one clip hypertensive dogs, but was significan tly attenuated in hypertensive dogs fed the nitric oxide synthase inhi bitor. These experiments demonstrated an important contribution of nit ric oxide in modulating the increased activity of the peripheral renin -angiotensin system during the evolution of renovascular hypertension. Furthermore, our data show that the evolution of this form of experim ental renal hypertension is accompanied by a magnification of the vaso dilator actions of angiotensin-(1-7). Activation of endothelium-derive d relaxing factors and angiotensin-(1-7) mechanisms may act in synergy to buffer the increase in vascular resistance produced by chronic ren al ischemia.