Stimulation of endothelial cell prostaglandin production by angiotensin peptides. Characterization of receptors.
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 II, angiotensin I, and [des-Phe8] angiotensin II [angiotensin-(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-stimulated 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 [Sar1,Ile8]angiotensin II, 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Jaiswal
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Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio 44195-5286.
Diz
D I
DI
Chappell
M C
MC
Khosla
M C
MC
Ferrario
C M
CM
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D009842:Oligopeptides / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D011725:Pyridines / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000145:classification*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D009842:Oligopeptides; D011453:Prostaglandins; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; C060894:CGP 42112A; C014805:angiotensin II, Sar(1)-Thr(8)-; D000803:Angiotensin I; D011464:Epoprostenol; D019808:Losartan; D015232:Dinoprostone