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Am J Physiol Heart Circ Physiol 284: H779-H789, 2003. First published November 7, 2002; doi:10.1152/ajpheart.00317.2002
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Vol. 284, Issue 3, H779-H789, March 2003

ANG II AT2 receptor modulates AT1 receptor-mediated descending vasa recta endothelial Ca2+ signaling

Kristie Rhinehart, Corey A. Handelsman, Erik P. Silldorff, and Thomas L. Pallone

Division of Nephrology, University of Maryland School of Medicine, Baltimore 21201-1595; and Department of Biology, Towson University, Towson, Maryland 21252

We tested whether the respective angiotensin type 1 (AT1) and 2 (AT2) receptor subtype antagonists losartan and PD-123319 could block the descending vasa recta (DVR) endothelial intracellular calcium concentration ([Ca2+]i) suppression induced by ANG II. ANG II partially reversed the increase in [Ca2+]i generated by cyclopiazonic acid (CPA; 10-5 M), acetylcholine (ACh; 10-5 M), or bradykinin (BK; 10-7 M). Losartan (10-5 M) blocked that effect. When vessels were treated with ANG II before stimulation with BK and ACh, concomitant AT2 receptor blockade with PD-123319 (10-8 M) augmented the suppression of endothelial [Ca2+]i responses. Similarly, preactivation with the AT2 receptor agonist CGP-42112A (10-8 M) prevented AT1 receptor stimulation with ANG II + PD-123319 from suppressing endothelial [Ca2+]i. In contrast to endothelial [Ca2+]i suppression by ANG II, pericyte [Ca2+]i exhibited typical peak and plateau [Ca2+]i responses that were blocked by losartan but not PD-123319. DVR vasoconstriction by ANG II was augmented when AT2 receptors were blocked with PD-123319. Similarly, AT2 receptor stimulation with CGP-42112A delayed the onset of ANG II-induced constriction. PD-123319 alone (10-5 M) showed no AT1-like action to constrict microperfused DVR or increase pericyte [Ca2+]i. We conclude that ANG II suppression of endothelial [Ca2+]i and stimulation of pericyte [Ca2+]i is mediated by AT1 or AT1-like receptors. Furthermore, AT2 receptor activation opposes ANG II-induced endothelial [Ca2+]i suppression and abrogates ANG II-induced DVR vasoconstriction.

kidney; vasoconstriction; vasodilation; medulla; blood flow


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