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 A^-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 angiotensin 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 19J±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~',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 ftg/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;/?<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. 3 Some of these factors, such as endothelium-derived relaxing factor (EDRF), endothelin, and prostacyclin (PGI 2 ), are endogenous products of the renal endothelium. The importance of EDRF, presumably nitric oxide or an NO-containing compound, 4 -6 in maintaining normal renal blood flow (RBF) has been demonstrated by a number of investigators. Inhibition of EDRF synthesis using either N -nitro-L-arginine methyl ester (L-NAME) or /V°-monomethyl-L-arginine (L-NMMA) 7 presence of a large increase in renal perfusion pressure (i.e., blood pressure). Baylis et al 9 have demonstrated in rats that the decrease in RBF caused by inhibition of EDRF synthesis was accompanied by a disproportionate decrease in glomerular filtration rate (GFR) compared with the change in RBF, resulting in an increased filtration fraction (FF). These investigators suggested that under basal conditions, tonic release of EDRF is important in maintaining normal RBF and renal function. Previous studies using direct intrarenal infusion of angiotensin II (Ang II) 13 -15 resulted in decreased RBF and GFR but increased FF. Similar disproportionate chang...

Nitric oxide influences blood flow distribution in renovascular hypertension.

“…We have previously reported that in anesthetized normotensive rats, acute blockade of Ang II largely diminished the increase in renal vascular resistance seen with EDNO synthesis inhibition, 14 ' 15 suggesting that local EDNO production balances the renal vasoconstrictor effect of Ang II and thereby maintains renal blood flow. Based on these observations, we hypothesized that in 2K1C hypertension with elevated Ang II but only mild renal artery stenosis, EDNO should have a greater influence on regional blood flow compared with normotensive controls.…”

“…7 In various models of hypertension, including two-kidney, one clip (2K1C) Goldblatt, 1 aortic coarctation, 14 Dahl salt-sensitive, 3 and deoxycorticosterone acetate-salt 1 hypertension as well as in genetically spontaneously hypertensive rats, 2 endothelium-dependent vascular relaxation in vitro is impaired but may be restored by reversing the hypertension. 1 These observations suggest that endothelial dysfunction associated with hypertension may be due to insufficient production of the intrinsic vasodilator endothelium-derived nitric oxide (EDNO).…”

Cardiovascular and Renal Phenotype in Mice With One or Two Renin Genes

“…We then inhibited NOS because we have found that, in anesthetized rats 18 and mice, 14 the decrease in RBF after L-NAME was dependent on the renin-angiotensin system. We did observe that the renal vasoconstrictor response in Sv-129 was significantly greater than in C-57, despite their lower PRC.…”

“…First, we compared the pressor and renal vasoconstrictor response to a 10-mg/kg bw blocking dose of L-NAME 12,18 in the two strains. Additionally, changes in RBF in response to sequential decreases in renal perfusion pressure were monitored using an adjustable aortic constrictor as previously described.…”

Pressure Natriuresis in AT2 Receptor–Deficient Mice with L-NAME Hypertension

“…The physiologic results on sodium and water reabsorption and renal hemodynamic may have been aggravated in AT 2 Ϫ/Ϫ mice by the deletion of the AT 2 receptor and the upregulation of the AT 1 receptor. In rats, AT 1 receptor blockade reduced or abolished the renal vasoconstriction after L-NAME treatment (28,29). The AT 2 receptor mediates vasodilation and sodium excretion and opposes the effects of AT 1 receptor stimulation.…”