In anesthetized rats, renal perfusion is largely regulated by a balance between the vasodilator influence of endothelium-derived nitric oxide (EDNO) and angiotensin II (AII)-mediated vasoconstriction. However, in conscious rats, which are characterized by lower PRA, the influence of AII is largely dissipated. To determine whether chronically increasing PRA enhances the interaction between AII and EDNO in regulating renal perfusion, radioactive microspheres were used to assess RBF in conscious sodium-depleted rats. PRA of control rats on a standard diet was 2.3 +/- 0.3 ng of AI/mL per hour compared with 16.8 +/- 1.5 ng of AI/mL per hour (P < 0.001) for rats on a sodium-restricted diet. In 12 rats on a standard diet, the inhibition of EDNO synthesis with L-Nw-nitroarginine methyl ester (L-NAME) increased blood pressure (BP) from 111 +/- 2 to 135 +/- 3 (P < 0.001) and decreased RBF by 47% (from 8.0 +/- 0.6 to 4.3 +/- 0.3 mL/min per gram kidney wt; P < 0.001). Renal vascular resistance (RVR) increased by 132% (from 14.9 +/- 1.2 to 34.7 +/- 3.3 resistance units (RU); P < 0.001). Pretreatment with Losartan, an AII receptor antagonist, did not modify the changes in BP, RBF, and RVR induced by L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)