CORONARY-ARTERY CONSTRICTION BY THE ISOPROSTANE 8-EPI PROSTAGLANDIN-F2-ALPHA

1 This study was undertaken to compare the effects of 8-epi prostaglan din F-2 alpha (8-epi PGF(2 alpha)) to those of prostaglandin F-2 alpha (PGF(2 alpha)) and U46619, a thromboxane mimetic, on ovine, bovine an d porcine coronary arteries. 2 8-epi PGF(2 alpha) constricted porcine and bovine coronary arteries in a concentration-dependent manner with EC(50) values of 689.0 +/- 229.3 and 1361.0 +/- 272.3 nM, respectively , but had no effect on ovine coronary arteries. 3 U46619 was a potent vasoconstrictor of porcine, ovine and bovine coronary arteries with EC (50) values of 33.0 +/- 23.5, 373.3 +/- 69.7 and 254.1 +/- 134.3 nM, r espectively. E(max) values were significantly greater than those obtai ned with 8-epi PGF(2 alpha). 4 PGF(2 alpha) constricted porcine and bo vine coronary arteries in a concentration-dependent manner with EC(50) values of 1631.0 +/- 207.6 and 3644.0 +/- 344.8 nM, respectively, but had no effect on ovine coronary arteries. 5 Concentration-dependent c onstriction to U46619 in porcine coronary arteries was competitively i nhibited by SQ29548 (10(-8) M to 10(-7) M) and BM13505 (10(-8) M to 10 (-6) M) with no decrease in maximal responses. 6 Concentration-depende nt constriction to 8-epi PGF(2 alpha) in porcine coronary arteries was inhibited in a concentration-dependent manner by SQ29548 (10(-8) M to 10(-7) M) and BM13505 (10(-8) M to 10(-6) M). However, the inhibition was associated with a decrease in maximal response. 6 Concentration-d ependent constriction to 8-epi PGF(2 alpha) in porcine coronary arteri es was inhibited in a concentration-dependent manner by SQ29548 (10(-8 ) M to 10(-7) M) and BM13505 (10(-8) M to 10(-6) M). However, the inhi bition was associated with a decrease in maximal response. 7 Maximal r esponses of porcine coronary artery to U46619 (1 mu M) and 8-epi PGF(2 alpha), (30 mu M) were inhibited in a concentration-dependent manner by SQ29548 with IC50 values 99 +/- 12.36 nM and 46.5 +/- 18.67 nM, res pectively. 8 Although ovine coronary arteries did not constrict to 8-e pi PGF(2 alpha) pre-incubation of these vessels with 8-epi PGF(2 alpha ) caused a rightward shift of the U46619 response curve in a concentra tion-dependent manner. 9 Pre-incubation of porcine coronary arteries w ith 8-epi PGF(2 alpha) competitively inhibited responses to U46619 wit h a Schild slope of 0.99 and a pA(2) of 6.13. 10 We conclude that 8-ep i PGF(2 alpha) is a vasoconstrictor within porcine and bovine coronary arteries, with a potency approximately twice that of PGF(2 alpha) but 5-20 times lower than U46619. The data suggest that 8-epi PGF(2 alpha ) is acting as a partial agonist on the TP-receptor in the coronary va sculature.