(Hypertension. 1996;27:1173-1179.)
© 1996 American Heart Association, Inc.
Articles |
Role of Nitric Oxide in Short-term and Prolonged Effects of Angiotensin II on Renal Hemodynamics
From the Division of Nephrology and Hypertension, Georgetown University School of Medicine, Washington, DC.
Correspondence to Christopher S. Wilcox, MD, PhD, Georgetown University Medical Center, Division of Nephrology and Hypertension, 3800 Reservoir Rd NW, PHC F6003, Washington, DC 20007.
Abstract Short-term infusions of angiotensin II (Ang II) increase renal vascular 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 from renal excretion of nitrate and nitrite, percent increases in renal vascular resistance during inhibition of NO synthase with intravenous NG-nitro-L-arginine methyl ester (L-NAME), or decreases in renal vascular resistance during stimulation of endothelial NO synthase with intravenous 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 and renal vascular resistance and reductions in renal blood flow. Captopril was administered for 3 to 4 days to suppress Ang II generation. The renal excretion of nitrate and nitrite was increased during short-term Ang II infusions (from 205±22 to 331±58 pmol·min-1, P<.05) but was unchanged during prolonged Ang II infusion (control group, 197±33 versus Ang II, 245±42 pmol·min-1, P=NS). The percent increase in renal vascular resistance with L-NAME was potentiated dose dependently by short-term but not long-term Ang II infusions. The increase in renal vascular resistance with L-NAME in control rats without Ang II 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 resistance was significantly (P<.01) increased compared with controls in short-term Ang II–infused rats (+369±70%) but was not significantly different in prolonged infused rats (+190±33%). Intravenous acetylcholine caused dose-dependent renal vasodilation that was not significantly changed in rats receiving short-term intravenous Ang II but was significantly (P<.005) potentiated in those receiving prolonged Ang II infusions (change in renal vascular resistance with acetylcholine at 10 µg·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 blood pressure and renal blood flow and hence presumably equivalent increases in endothelial shear stress. However, only short-term Ang II infusions increased NO generation and the dependence of the renal circulation on NO, whereas acetylcholine-induced NO release was enhanced selectively during long-term Ang II infusions. This suggests that during long-term Ang II, renal NO release may become uncoupled from shear stress yet remains highly responsive to receptor-mediated stimulation.
Key Words: nitric oxide • angiotensin II • renal blood flow • vascular resistance • L-NAME
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