Role of AT₁receptors in the renal papillary effects of acute and chronic nitric oxide inhibition

Abstract

Nitric oxide (NO) is a vasodilator substance controlling renal papillary blood flow (PBF) in the rat. In this study we have evaluated the role of AT1 angiotensin II receptors as modulators of the whole kidney and papillary vasoconstrictor effects induced by the acute or chronic inhibition of NO synthesis. Experiments have been performed in anesthetized, euvolemic Munich-Wistar rats prepared for the study of renal blood flow (RBF) and PBF. In normal rats, acute administration of the NO synthesis inhibitor N ω-nitro-l-arginine methyl ester (l-NAME) increased mean arterial pressure (MAP) and decreased RBF and PBF. Either acute or chronic treatment with the AT1 receptor blocker losartan did not modify the decreases in RBF or PBF secondary to l-NAME. In animals made hypertensive by chronic inhibition of NO, basal MAP was higher, whereas RBF and PBF were lower than in the controls. In these animals, acute or chronic administration of losartan decreased MAP and increased both RBF and PBF significantly. These results indicate that, under normal conditions, the decreases in RBF or PBF induced by the acute inhibition of NO synthesis are not modulated by AT1-receptor stimulation. However, the arterial hypertension, renal vasoconstriction, and reduced PBF present in chronic NO-deficient hypertensive rats is partially due to the effects of angiotensin II, via stimulation of AT1-receptors.

Effect of losartan on renal microvasculature during chronic inhibition of nitric oxide visualized by micro-CT

“…The decreases in vascular volume fraction were greater in the medulla than in the cortex. This is in agreement with cortical and medullary blood flow measurements made in previous studies (21,23). In the present study, the increase in blood pressure was not accompanied by a concomitant increase in sodium excretion.…”

“…A decrease in vascular filling, as a result of vascular rarefaction, would contribute to the increase in vascular resistance and hypoperfusion seen in the physiological part of this study as well as in previous studies published by us (21). The decreases in vascular volume fraction were greater in the medulla than in the cortex.…”

“…These results are in agreement with the fact that the cortical and outer medullary circulation is mainly dependent on ANG II AT 1 receptors and that the inner medullary (papillary) circulation is highly dependent on NO availability. Previous studies (21,23) showed that when NO was inhibited, the effects of ANG II on papillary circulation were small and appeared not to be an important controller of papillary blood flow. Furthermore, Zou and Cowley (38) showed that ANG II binding sites were absent in the inner medulla and were located primarily in the interstitial cells of the outer medulla located between the tubules and vasa recta.…”

“…During initial phases of NO inhibition, it is probable that the reductions in intrarenal blood flow are a result of vasoconstriction (21). However, during chronic NO inhibition, it is probable that the initial vasoconstriction progresses to rarefaction of the microvasculature as a consequence of pathological changes related to hypoperfusion.…”

“…In vivo experiments (23) showed that NO modulated the ANG II response of cortical but not outer medullary blood flow. However, Ortiz et al (21) demonstrated that in contrast to acute studies, chronic inhibition of NO synthesis caused a marked decrease in papillary flow, which was partially normalized by chronic blockade of AT 1 receptors with losartan.…”