CONTRIBUTION OF ANGIOTENSIN-II TO RENAL HEMODYNAMIC AND EXCRETORY RESPONSES TO NITRIC-OXIDE SYNTHESIS INHIBITION IN THE RAT

This study was performed to evaluate the contribution of angiotensin II to the effects of nitric oxide (NO) synthesis inhibition on renal hemodynamics and excretory function in rats. Intravenous infusion of N(omega)-nitro-L-arginine (NLA; 20 mug/100 g.min) increased renal arterial pressure (RAP) from 128 +/- 2 to 143 +/- 3 mm Hg (P < 0.05; N = 6) and decreased RBF by 64 +/- 3% (P < 0.01) and GFR by 41 +/- 5% (P < 0.05). In response to reduction of RAP to control levels (127 +/- 2 mm Hg) by means of an adjustable clamp (CL) placed on the suprarenal aorta, RBF and GFR exhibited efficient autoregulation and were not altered. In rats (N = 6) pretreated with the AT1 angiotensin II receptor antagonist losartan (10 mg/kg iv), the infusion of NLA increased RAP (from 114 +/- 1 to 135 +/- 2 mm Hg; P< 0.05) and decreased RBF by 42 +/- 3% (P < 0.05). However, NLA did not decrease GFR in the losartan-treated rats. As in the control rats, the reduction of RAP to 113 +/- 1 mm Hg elicited autoregulatory responses that maintained RBF and GFR. In the untreated rats, at similar RAP (128 +/- 2 (control) versus 127 +/- 2 mm Hg (NLA + CL)), NO synthesis inhibition decreased urine flow and sodium excretion (P < 0.05, in both cases). However, during blockade of AT, receptors, NLA infusion failed to decrease urine flow and sodium excretion, even when RAP was controlled (114 +/- 1 (control) versus 113 +/- 1 mm Hg (NLA + CL)). When RAP was held constant, NLA infusion increased renal tissue angiotensin II content (558 +/-64 versus 827 +/- 74 fmol/g; P < 0.05; N = 5). These findings indicate that AT, receptor activation by endogenous angiotensin II contributes to the reductions in RBF, GFR, and sodium excretion observed during NO synthesis inhibition in the rat.