Angiotensin dependence of endothelium-mediated renal hemodynamics

Abstract

Endothelium-derived relaxing factor has been shown to regulate renal blood flow, and inhibition of its synthesis increases blood pressure and renal vascular resistance and decreases renal blood flow. Using the substrate antagonist NW-nitro-L-arginine methyl ester (L-NAME), we tested whether renal vasoconstriction induced by endothelium-derived relaxing factor synthesis inhibition could be mediated in part by aogiotensin II. In 14 control rats, 10 mg/kg body wt L-NAME increased blood pressure from 106±6 to 126±6 mm Hg (p<0.001), increased renal vascular resistance by 74% (from 19.3±2.6 to 33.6±2.9 resistance units), and decreased renal blood flow by 34% (from 5.9±0.5 to 3.9±0.3 ml · min-1 · g kidney wt-1, p<0.005). When six rats were treated with 10 mg/kg body wt of the angiotensin receptor antagonist DuP 753, L-NAME increased blood pressure from 84±4 to 106±4 mm Hg (p<0.001); however, renal vascular resistance increased by only 27% (from 13±2 to 17±3 resistance units, p<0.01; p<0.05 different from control value) and renal blood flow was unchanged. Likewise, after pretreatment of six rats with 32 μg/100 g body wt of the angiotensin converting enzyme inhibitor enalaprilat, L-NAME increased blood pressure from 88±5 to 124±6 mm Hg (p<0.001) and renal vascular resistance by 54% (from 12±1 to 18±3 resistance units, p<0.01; p<0.05 different from control value) but renal blood flow was unchanged. Additionally, in enalaprilat-treated rats L-NAME caused a transient increase in renal blood flow that was not apparent in rats pretreated with a kinin analogue antagonist or indomethacin. Thus, inhibition of endothelium-derived relaxing factor synthesis produces an angiotensin-mediated decrease in renal blood flow that is independent of L-NAME's systemic pressor effect. This suggests that renal endotheliumderived relaxing factor buffers the vasoconstrictor influence of endogenous angiotensin, particularly in the kidney.