ROLE OF NITRIC-OXIDE IN LONG-TERM ANGIOTENSIN-II-INDUCED RENAL VASOCONSTRICTION

In vitro studies have indicated that nitric oxide may play an important role in modulating the renal vascular actions of angiotensin II (Ang II). However, the physiological importance of this interaction in the long-term regulation of renal hemodynamics is unknown. Therefore, the goal of this study was to determine if long-term Ang II-induced renal vasoconstriction was potentiated by nitric oxide synthesis inhibition. The intrarenal effects of Ang II were examined in eight unilaterally nephrectomized, conscious dogs before and after systemic inhibition of nitric oxide synthesis. Ang II infusion into the renal artery at 0.5 ng/kg per minute resulted in decreases in renal plasma flow of 15% and 9% after 3 and 5 days, respectively. During this time, glomerular filtration rate decreased 12% after 3 days of angiotensin but was not significantly changed after 5 days. After 4 days of recovery from Ang II, nitric oxide synthesis was inhibited with intravenous N(G)-nitro-L-arginine-methyl ester (L-NAME) at 10 mug/kg per minute for 5 days, and this caused a significant decrease in renal plasma flow but no change in glomerular filtration rate. Infusion of Ang II into L-NAME-pretreated dogs for an additional 5 days further decreased renal plasma flow and glomerular filtration 14% and 11%, respectively. However, the effects of Ang II and L-NAME on renal plasma flow were only additive on days 3 and 5 of this period, and the effects on glomerular filtration were additive on day 3 but were potentiated on day 5. Neither iothalamate space, plasma renin activity, plasma aldosterone concentration, nor plasma cortisol concentration was changed during the experiment, and a marked decrease in the acetylcholine depressor response during L-NAME indicated significant nitric oxide synthesis inhibition. In conclusion, long-term inhibition of nitric oxide synthesis did not potentiate the Ang II-induced reduction in renal plasma flow, but by the end of the angiotensin and nitric oxide inhibition periods, the effects of angiotensin on glomerular filtration were potentiated.