Phospholipase inhibition and the mechanism of angiotensin-induced prostacyclin release from rat mesenteric vasculature

Autor: T.J. Martin, Gregory J. Dusting, R.D. Nolan
Rok vydání: 1981
Předmět:
Zdroj: Biochemical pharmacology. 30(15)
ISSN: 0006-2952
Popis: Generation of prostaglandins by arterial vasculature of rats was measured by perfusing the isolated mesenteric arterial vascular bed with Krebs-Henseleit solution. The effluent directly superfused bioassay tissues in cascade, and aliquots were collected for subsequent chromatography and radioimmunoassay. Injection of arachidonate (1–10 μg) or angiotensin II (0.1–0.5 μg) through the mesentery caused release of a PGI2-like substance. After extraction and Chromatographic separation of the mesenteric effluent, it was confirmed by radioimmunoassay that 6-oxo-PGF1α (the hydration production of PGI2) is the predominant prostanoid generated from exogenous arachidonate. Release of 6-oxo PGF1α and PGE2 from mesentery was also stimulated by injection of angiotensin II (0.05–0.5 μg). Treatment of the mesentery with indomethacin (1 μg/ml) abolished all effects of angiotensin II and arachidonate. Perfusion of the mesentery with dexamethasone (3 μg/ml) or mepacrine (33 μg/ml) both of which have been reported to inhibit phospholipase A2 activity, reduced PGI2 release induced by angiotensin II, but did not affect conversion of exogenous arachidonate. It is concluded that PGI2 is the major prostanoid generated in perfused mesenteric arterial vasculature of rats, and angiotensin II releases PGI2 by activation of a phospholipase.
Databáze: OpenAIRE