Coronary artery constriction by the isoprostane 8‐epi prostaglandin F2α

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Abstract
1 This study was undertaken to compare the effects of 8-epi prostaglandin F2α (8-epi PGF2α) to those of prostaglandin F2α (PGF2α) and U46619, a thromboxane mimetic, on ovine, bovine and porcine coronary arteries. 2 8-epi PGF2α constricted porcine and bovine coronary arteries in a concentration-dependent manner with EC50 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 EC50 values of 33.0 ± 23.5, 373.3 ± 69.7 and 254.1 ± 134.3 nM, respectively. Emax values were significantly greater than those obtained with 8-epi PGF2α. 4 PGF2α constricted porcine and bovine coronary arteries in a concentration-dependent manner with EC50 values of 1631.0 ± 207.6 and 3644.0 ± 344.8 nM, respectively, but had no effect on ovine coronary arteries. 5 Concentration-dependent constriction to U46619 in porcine coronary arteries was competitively inhibited 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-dependent constriction to 8-epi PGF2α 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. 7 Maximal responses of porcine coronary artery to U46619 (1 μm) and 8-epi PGF2α (30 μm) were inhibited in a concentration-dependent manner by SQ29548 with IC50 values 99 ± 12.36 nM and 46.5 ± 18.67 nM, respectively. 8 Although ovine coronary arteries did not constrict to 8-epi PGF2α, pre-incubation of these vessels with 8-epi PGF2α caused a rightward shift of the U46619 response curve in a concentration-dependent manner. 9 Pre-incubation of porcine coronary arteries with 8-epi PGF2aL competitively inhibited responses to U46619 with a Schild slope of 0.99 and a pA2 of 6.13. 10 We conclude that 8-epi PGF2α is a vasoconstrictor within porcine and bovine coronary arteries, with a potency approximately twice that of PGF2α but 5–20 times lower than U46619. The data suggest that 8-epi PGF2α is acting as a partial agonist on the TP-receptor in the coronary vasculature.