Influence of Plasma Insulin Levels on Antinatriuretic and Vasoconstrictor Actions of Angiotensin‐II

The objective of the present study is to investigate whether plasma insulin levels play a role in the antinatriuretic and vasoconstrictor actions of angiotensin-II (Ang-II). We evaluated antinatriuretic function of endogenous Ang-II using an AT1 receptor antagonist, candesartan in anesthetized Sprague-Dawley rats. In control rats, candesartan produced significant increases in natriuresis and diuresis and these effects were abolished in streptozocin (STZ, 55 mg/kg i.p.) treated rats. Replacement of insulin restored these renal effects of candesartan. In a separate group of rats pretreated with an autonomic ganglionic blocker, pressor responses to Ang-II and norepinephrine (NE) before or after L-NNA, a nitric oxide synthase inhibitor were not affected by STZ treatment. However, insulin replacement greatly augmented these responses. These data provide evidence in vivo showing that insulin can enhance both antinatriuretic and vasoconstrictor actions of Ang-II. Hence exaggerated renal and vascular effects of Ang-II in the obese Zucker rats observed in our previous studies may be related to hyperinsulimemia and this phenomena could contribute to salt-sensitivity and development of sustained hypertension.