This study examined the role of ANG II in modulating the increase of hematocrit and vascular permeability that follows nitric oxide (NO) synthesis blockade, that are contributing to the decrease in cardiac index (CI) in conscious, chronically catheterized rats. Pretreatment with losartan attenuated the N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced increase in total peripheral resistance by 26% and also blunted the fall in CI (28%) and stroke volume. L-NAME produced an increase in hematocrit (4.5%) and in (125)I-labeled albumin content in the heart and small intestine in untreated rats, but the increase was prevented in rats pretreated with losartan. Furthermore, L-NAME induced a transient increase of plasma protein concentration and tissue intestinal blood flow, which was abolished in rats given losartan. The results of the present study indicate that the systemic hemodynamic responses, the fall in plasma volume, and the increase in albumin escape observed after inhibition of NO synthesis are in part the consequence of unmasking the actions of endogenous ANG II. These data suggest a physiological role for NO by restraint of the vascular actions of the renin-angiotensin system.