ROLE OF NITRIC-OXIDE IN SHORT-TERM AND PROLONGED EFFECTS OF ANGIOTENSIN-II ON RENAL HEMODYNAMICS

Short-term infusions of angiotensin II (Ang II) increase renal vascula r resistance and thereby endothelial shear stress and nitric oxide (NO ) release. Prolonged stimulation of Ang II can decrease the expression of NO synthase isoforms in the macula densa, but prolonged increases in shear stress can increase transcription of endothelial NO synthase. Therefore, we designed these studies to test the hypothesis that Ang II exerts time-dependent effects on renal NO generation as assessed fr om renal excretion of nitrate and nitrite, percent increases in renal vascular resistance during inhibition of NO synthase with intravenous N-G-nitro-L-arginine methyl ester (L-NAME), or decreases in renal vasc ular resistance during stimulation of endothelial NO synthase with int ravenous acetylcholine. Rats were tested during graded short-term (30 to 90 minutes intravenous) or prolonged (5 to 6 days subcutaneous) Ang II infusions that led to dose-dependent increases in blood Pressure a nd renal vascular resistance and reductions in renal blood flow. Capto pril was administered for 3 to 4 days to suppress Ang II generation. T he renal excretion of nitrate and nitrite was increased during short-t erm Ang II infusions (from 205+/-22 to 331+/-58 pmol . min(-1), P<.05) but was unchanged during prolonged Ang II infusion (control group, 19 7+/-33 versus Ang II, 245+/-42 pmol min(-1), P=NS). The percent increa se in renal vascular resistance with L-NAME was potentiated dose depen dently by short-term but not long-term Ang II infusions. The increase in renal vascular resistance with t-NAME in control rats without Ang I I infusions was +150+/-13%. At an Ang II infusion of 200 ng . kg(-1). min(-1), the L-NAME-induced percent increase in renal vascular resista nce was significantly (P<.01) increased compared with controls in shor t-term Ang II-infused rats (+369+/-70%) but was not significantly diff erent in prolonged infused rats (+190+/-33%). Intravenous acetylcholin e caused dose-dependent renal vasodilation that was not significantly changed in rats receiving short-term intravenous Ang II but was signif icantly (P<.005) potentiated in those receiving prolonged Ang II infus ions (change in renal vascular resistance with acetylcholine at 10 mu g . kg(-1). min(-1) versus control, -21.5+/-5.0%; with short-term Ang II, -24.9+/-4.5%; with long-term Ang II, -52.1+/-7.2%). In conclusion, short- and long-term Ang II infusions caused equivalent changes in bl ood pressure and renal blood flow and hence presumably equivalent incr eases in endothelial shear stress. However, only short-term Ang II inf usions increased NO generation and the dependence of the renal circula tion on NO: whereas acetylcholine-induced NO release was enhanced sele ctively during long-term Ang II infusions. This suggests that during l ong-term Ang II, renal NO release may become uncoupled from shear stre ss yet remains highly responsive to receptor-mediated stimulation.