HYPERTENSION INDUCED BY CHRONIC RENAL ADRENERGIC-STIMULATION IS ANGIOTENSIN DEPENDENT

We designed these studies to assess the role of the renin-angiotensin system in mediating the hypertensive and renal functional effects of c hronic renal adrenergic stimulation. Norepinephrine was infused at 0.1 mu g/kg per minute for 7 days directly into the renal artery of unine phrectomized dogs under control conditions (n=5) or after plasma angio tensin II (Ang II) concentration was fixed at control levels (n=5) by chronic intravenous infusion of captopril (14 mu g/kg per minute) and Ang II (0.58+/-0.04 ng/kg per minute). During the first 60 minutes of norepinephrine infusion in control dogs, mean arterial pressure increa sed 9+/-4 mm Hg in association with a twofold to threefold rise in pla sma renin activity. Additionally, glomerular filtration rate, renal pl asma flow, sodium excretion, and fractional sodium excretion decreased to 70+/-5%, 64+/-5%, 31+/-4%, and 38+/-6% of control, respectively, w hile filtration fraction increased 15+/-2%. In contrast to the pronoun ced short-term effects of norepinephrine on renal function, during chr onic norepinephrine infusion, all indexes of renal function returned t o control levels. However, elevations in both plasma renin activity an d mean arterial pressure were sustained and on day 7 were 2.3+/-0.6 ng angiotensin I/mL per hour (control, 0.5+/-0.1) and 110+/-7 mm Hg (con trol, 90+/-3). in dogs with fixed plasma levels of Ang II, acute and c hronic changes in renal function induced by norepinephrine were simila r to those in control dogs except that acute reductions in glomerular filtration rate tended to be more severe, and changes in filtration fr action and fractional sodium excretion were either attenuated or aboli shed. Moreover, in the absence of a rise in plasma Ang II concentratio n, mean arterial pressure did not change either acutely or chronically during norepinephrine infusion. These findings suggest a critical rol e for Ang II in mediating the hypertension associated with elevated le vels of renal adrenergic stimulation that have little or no long-term effect on renal blood flow.