Transformation of arachidonic acid and prostaglandin endoperoxides by the guinea pig heart. Formation of RCS and prostacyclin.
The metabolism of arachidonic acid (AA) was studied in perfused isolated hearts from guinea pigs. The coronary effluent was continuously bioassayed for prostaglandin-like substances (PLS) using the cascade technique of Vane. Injections of AA in doses between 1--50 microgram into the perfusion fluid prior to the heart produced vasodilatation of the coronary vascular bed followed by a contraction of the rat stomach strip (RSS), chick rectum (CR) and rat colon (RC) as well as relaxation of the bovine coronary artery (BCA). At the higher doses of AA there was also contraction of the rabbit aorta (RbA). The same pattern of effects on the bioassay tissues was seen when prostaglandin endoperoxide (PGH2) was perfused through the heart. The response of the bank of superfused tissues provided evidence for the formation of prostacyclin (PGX or PGI2), PGE2 and PGF2alpha. Chromatographic studies showed that 6-oxo-PGF1alpha together with other prostaglandins was present in the perfusate after acidification, which suggested that the bovine coronary relaxing substance consists mainly of PGI2. Moreover, the rabbit aorta contracting substance (RCS) released in the perfusate was due to prostaglandin endoperoxides and not to thromboxane (TXA2). The formation of PLS from AA was completely blocked after treatment of the heart with the cyclo-oxygenase inhibitors, indomethacin or meclofenamic acid. Pretreatment of the heart with 15-hydroperoxyarachidonic acid (15-HPAA), a selective inhibitor of prostacyclin synthetase, inhibited the effect of AA on the coronary vasculature and diverted the metabolic transformation of AA towards PGE2 and PGF2alpha.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D003326:Coronary Circulation / Q000187:drug effects; D011464:Epoprostenol / Q000096:biosynthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011449:Prostaglandin Endoperoxides / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000096:biosynthesis / Q000494:pharmacology; D011463:Prostaglandins H / Q000378:metabolism; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D001095:Arachidonic Acids; D011449:Prostaglandin Endoperoxides; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D011463:Prostaglandins H; D013931:Thromboxanes; D013928:Thromboxane A2; D011464:Epoprostenol