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 chronic renal adrenergic stimulation. Norepinephrine was infused at 0.1 mu g/kg per minute for 7 days directly into the renal artery of uninephrectomized dogs under control conditions (n=5) or after plasma angiotensin 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 increased 9+/-4 mm Hg in association with a twofold to threefold rise in plasma renin activity. Additionally, glomerular filtration rate, renal plasma flow, sodium excretion, and fractional sodium excretion decreased to 70+/-5%, 64+/-5%, 31+/-4%, and 38+/-6% of control, respectively, while filtration fraction increased 15+/-2%. In contrast to the pronounced short-term effects of norepinephrine on renal function, during chronic norepinephrine infusion, all indexes of renal function returned to control levels. However, elevations in both plasma renin activity and 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 (control, 90+/-3). in dogs with fixed plasma levels of Ang II, acute and chronic changes in renal function induced by norepinephrine were similar to those in control dogs except that acute reductions in glomerular filtration rate tended to be more severe, and changes in filtration fraction and fractional sodium excretion were either attenuated or abolished. Moreover, in the absence of a rise in plasma Ang II concentration, mean arterial pressure did not change either acutely or chronically during norepinephrine infusion. These findings suggest a critical role for Ang II in mediating the hypertension associated with elevated levels of renal adrenergic stimulation that have little or no long-term effect on renal blood flow.