Prostacyclin (PGI2) release accompanying angiotensin conversion in rat mesenteric vasculature.
The relationship between angiotensin conversion and release of prostaglandins (PGs) were studied in isolated, perfused, mesenteric vasculature of rats. PGs in the mesenteric effluent were detected by bovine coronary artery and rat stomach strip, and by radioimmunoassay of 6-oxo-PGF1 alpha and PGE2. Angiotensin II (AII) was assayed simultaneously using rabbit aorta. Both angiotensin I (AI) and AII released a prostacyclin (PGI2)-like substance, but little PGE2 from the mesentery, AII being 5 times more potent. Indomethacin (2.8 micrometers) abolished angiotensin-induced release of PGI2. Of the AI (0.2--1.5 nmol) injected into the perfusion medium, 3--8% was converted to AII in passage through the mesentery. Captopril (4 micrometers), infused through the mesentery, inhibited AI-induced PGI2 release, but did not affect release induced by AII. Release of the PGI2-like substance by higher doses of AI (2--20 nmol) in the presence of captopril was always accompanied by concomitant contraction of rabbit aorta, indicating residual conversion of AI. Infusion of (Sar1, Ala8)AII (3--30 nM) through the mesentery abolished PGI2 release by both peptides. By choosing doses of AI and AII which produce equivalent amounts of AII in the mesenteric effluent, it appeared that AII generated locally in the mesenteric vasculature was a more effective stimulus for PGI2 generation than AII in the perfusion fluid. There is no evidence for intrinsic activity of AI, and release of the PGI2-like substance appears to be mediated through an AII receptor.
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000096:biosynthesis; D000809:Angiotensins / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D012504:Saralasin / Q000494:pharmacology
D000809:Angiotensins; D011453:Prostaglandins; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D011464:Epoprostenol; D012504:Saralasin