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

In vitro studies have indicated that nitric oxide may play an importan t 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 o f 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% an d 9% after 3 and 5 days, respectively. During this time, glomerular fi ltration rate decreased 12% after 3 days of angiotensin but was not si gnificantly changed after 5 days. After 4 days of recovery from Ang II , nitric oxide synthesis was inhibited with intravenous N(G)-nitro-L-a rginine-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-pretreat ed dogs for an additional 5 days further decreased renal plasma flow a nd glomerular filtration 14% and 11%, respectively. However, the effec ts of Ang II and L-NAME on renal plasma flow were only additive on day s 3 and 5 of this period, and the effects on glomerular filtration wer e additive on day 3 but were potentiated on day 5. Neither iothalamate space, plasma renin activity, plasma aldosterone concentration, nor p lasma 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 th e Ang II-induced reduction in renal plasma flow, but by the end of the angiotensin and nitric oxide inhibition periods, the effects of angio tensin on glomerular filtration were potentiated.