Mechanism of action of cyclosporine in preventing cardiac allograft rejection. II. Graft tissue levels of prostacyclin and thromboxane.
Four cyclo-oxygenase products (COP) of arachidonate were measured in tissue homogenates of rat cardiac allografts at intervals after transplantation. In rejecting graft tissue, there was a progressive decrease in the levels of prostaglandin E2 (PGE2) and PGF2 alpha from the time of grafting, which was accompanied by a rise in the levels of prostacyclin (PGI2, measured as its stable hydrolysis product 6-oxo-PGF1 alpha) and thromboxane A2 (TxA2, measured as its stable hydrolysis product TxB2). When the level of each individual COP in rejecting graft tissue was expressed as a percentage of the total COP measured, PGI2 and TxA2 increased from 9% to 36% and from 7% to 25%, respectively, from day three after grafting until the time of graft rejection. In contrast to these changes in COP levels in rejecting grafts, the levels of all four COP in nonrejecting allografts maintained by treatment of the graft recipients with cyclosporine remained normal--i.e., comparable to the levels in the recipients' own hearts.
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D015237:Dinoprost; D015232:Dinoprostone; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006084:Graft Rejection / Q000187:drug effects*; D016027:Heart Transplantation; D008297:Male; D011458:Prostaglandins E / Q000096:biosynthesis*; D011460:Prostaglandins F / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains / Q000276:immunology; D013929:Thromboxane B2 / Q000096:biosynthesis*; D014184:Transplantation, Homologous
D003524:Cyclosporins; D011458:Prostaglandins E; D011460:Prostaglandins F; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D011464:Epoprostenol; D015232:Dinoprostone