Coronary artery constriction by the isoprostane 8‐epi prostaglandin F2α

• Published in: British journal of pharmacology 1996-11, Vol.119 (6), p.1276-1280
• Main Authors: Kromer, Brendan M., Tippins, John R.
• Format: Article
• Language: English
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Biological and medical sciences; Blood vessels and receptors; Cattle; coronary artery disease; Coronary Vessels - drug effects; Coronary Vessels - physiology; Dinoprost - analogs & derivatives; Dinoprost - pharmacology; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; ischaemia; Isoprostane; oxidant stress; Phenylacetates - pharmacology; Prostaglandin Endoperoxides, Synthetic - pharmacology; Sheep; Sulfonamides - pharmacology; Swine; Thromboxane A2 - analogs & derivatives; Thromboxane A2 - pharmacology; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology; Vertebrates: cardiovascular system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1996.tb16033.x

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.