AngII AT 2 receptor modulates AT 1 mediated descending vasa recta endothelial Ca 2 + signaling

AngII AT2 receptor modulates AT1 mediated descending vasa recta endothelial Ca2+ signaling. We tested whether the respective AT1 and AT2 receptor subtype antagonists, losartan and PD123319 could block the descending vasa recta (DVR) endothelial intracellular calcium ([Ca]i) suppression induced by AngII. AngII partially reversed the increase in [Ca]i generated by cyclopiazonic acid (CPA, 10 M), acetylcholine (ACh, 10 M) or bradykinin (BK, 10 M). Losartan (10 M) blocked that effect. When vessels were treated with AngII prior to stimulation with BK and ACh, concomitant AT2 receptor blockade with PD123319 (10 M) augmented the suppression of endothelial [Ca]i responses. Similarly, preactivation with the AT2 agonist CGP42112A (10 M) prevented AT1 stimulation with AngII + PD123319 from suppressing endothelial [Ca]i. In contrast to endothelial [Ca]i suppression by AngII, pericyte [Ca]i exhibited typical peak and plateau [Ca]i responses that were blocked by losartan but not PD123319. DVR vasoconstriction by AngII was augmented when AT2 receptors were blocked with PD123319. Similarly, AT2 stimulation with CGP42112A delayed the onset of AngII induced constriction. PD123319 alone (10 M) showed no AT1 like action to constrict microperfused DVR or increase pericyte [Ca]i. We conclude that AngII suppression of endothelial [Ca]i and stimulation of pericyte [Ca]i is mediated by AT1 or AT1 like receptors. Furthermore, AT2 receptor activation opposes the AngII induced endothelial [Ca]i suppression and abrogates AngII induced DVR vasoconstriction.