Analysis of the Vasorelaxant Action of Angiotensin II in the Isolated Rat Renal Artery

Abstract

Abstract. Taking into consideration that mechanisms involved in the vasodilatator actions of angiotensin II have not yet been completely elucidated, the present study was undertaken in order to examine the mechanisms underlying the angiotensin II-induced relaxation of rat renal artery (RRA). Angiotensin II produced concentration-dependent and endothelium-independent relaxation of isolated RRA. Angiotensin II-induced relaxation was partially reduced by inhibitors of nitric oxide synthase and guanylyl cyclase. The remaining dilatation was inhibited by a potassium channel blocker, charybdotoxin. Precontraction of RRA with high concentration of K + partially reduced angiotensin II-evoked relaxation, while indomethacin, glibenclamide, apamin and barium did not alter the angiotensin II concentration-response curve. Losartan had no effect on angiotensin II effect. Oppositely, HOE 140 and PD123319, separately or in combination, partially antagonized vasorelaxation induced by angiotensin II. Complete blockade of RRA response was obtained after simultaneous incubation of all three receptor antagonists HOE-140, PD123319, and losartan; L-NOARG plus HOE-140; or PD123319 plus charybdotoxin. These results indicate that angiotensin II produces endothelium-independent relaxation of RRA, which is most probably mediated by the interaction of the NO-cGMP pathway and K + channels. Moreover, we can assume that AT 1 , AT 2 , and B 2 receptors are involved in the vasorelaxant effect of angiotensin II.

Hypoxia/Reoxygenation of Rat Renal Arteries Impairs Vasorelaxation via Modulation of Endothelium-Independent sGC/cGMP/PKG Signaling

“…Indomethacin, a COX pathways inhibitor, neither affected the relaxation to ACh of ILA, nor influenced the difference in the ACh response between H/R and control. This observation is in line with findings in isolated rat renal arteries and isolated perfused rat afferent arterioles ( Wang et al, 2003 ; Grbovic et al, 2008 ). In contrast, experiments in anesthetized rats revealed a 20–40% contribution of the indomethacin inhibited systems to the control of renal perfusion ( Dautzenberg and Just, 2013 ).…”

Endothelium-dependent relaxation factor released by perivascular adipose tissue

“…However, results on whether endothelium is involved in mediating the relaxation response of Ang II varied, because some reported that endothelium was involved [28][29][30][31][32] whereas others had found that endothelium was not involved [27,33]. Most of the studies had reported that stimulation of AT 2 receptors was involved in mediating the relaxation response [34]. Obviously, differences in the type of vessels and animal species may be some of the contributing factors in such contradicting findings.…”

Atorvastatin Protects Against Angiotensin II–induced Injury and Dysfunction in Human Umbilical Vein Endothelial Cells Through Bradykinin 2 Receptors

“…23,24 Most of the above-mentioned adverse actions of Ang II are mediated by AT1 receptors, which are widely expressed by most cell types. Previous results of Grbovic et al 25 have shown that activation of B2Rs contributes to Ang II-induced relaxation of isolated rat renal artery via NO/cGMP pathway. The precise mechanism underlying interaction between Ang II and B2Rs still remains unclear and angiotensin type 2 receptors may be involved.…”