Stimulation of endothelial cell prostaglandin production by angiotensin peptides: Characterization of receptors

Abstract

Angiotensin II stimulates prostaglandin release in blood vessels via activation of angiotensin receptors present in endothelium, vascular smooth muscle cells, or both. We evaluated the response of angiotensin n, angiotensin I, and [des-Phe8] angiotensin II [angjotensin-(1–7)] on prostaglandin release in porcine aortic endothelial cells. Incubation of cell monolayers with angiotensin I and angiotensin-(1–7), but not angiotensin II, stimulated the release of prostaglandin E2 and prostaglandin I2 in a dose-dependent manner (10−10 to 10−6 M) with an EC50 of approximately 1 nM. In addition, we characterized the angiotensin receptor subtypes mediating prostaglandin synthesis by using subtype-selective antagonists. Angiotensin I-stimuIated prostaglandin synthesis was not altered by either of the nonselective classical angiotensin receptor antagonists [Sar1,Thr8]angiotensin II or [Sar1,Ile8]angiotensin II. In contrast, either the angiotensin subtype 1 (AT1) antagonist DuP 753 or the subtype 2 (AT2) antagonist CGP42112A significantly attenuated the prostaglandin release in response to angiotensin I. However, PD123177, another AT2 antagonist, did not inhibit angiotensin I-stimulated prostaglandin release. Angiotensin-(1–7)-induced prostaglandin release was significantly attenuated by [Sar1,Thr8] angiotensin II (10−6 M) and PD123177 (10−6 M) but not by [Sar1Ile8] angiotensin H, DuP 753, or CGP42112A. Higher doses (10−5 M) of DuP 753 and CGP42112A attenuated the angiotensin-(1–7) response. These data suggest that in porcine aortic endothelial cells, angiotensin I and angiotensin-(1–7) but not angiotensin II are potent stimuli for prostaglandin synthesis. Angiotensin-(1–7)-stimulated prostaglandin synthesis occurs through activation of a receptor subtype distinct from AT1 and AT2 angiotensin receptor but recognizable by [Sar1,Thr8] angiotensin II or PD123177 and at high concentrations by both DuP 753 and CGP42112A. Because angiotensin II was devoid of agonistic actions for prostaglandin release and the nonselective classical peptide antagonists did not block the angiotensin I response, these findings suggest that angiotensin I does not act through an angiotensin II receptor. The explanation for the blockade of angiotensin I–stimulated prostaglandin synthesis by either AT1- or AT2-selective angiotensin receptor antagonists remains unknown. © 1992 American Heart Association, Inc.