Interaction of epoprostenol (PGI2) with vasoconstrictors on diameter of large coronary arteries of the dog.
The platelet release products thromboxane A2 (TxA2) and serotonin (5-HT) might contribute to coronary vasoconstriction in humans. We have examined the effects of a TxA2-like analogue (U46619), 5-HT, and epoprostenol (PGI2) on the left anterior descending coronary artery of the dog. Changes in diameter were measured by sonomicrometry during perfusion of the vessel with blood from a support dog, at constant flow and distal resistance. Intra-arterial infusions of 5-HT (0.01-1 mumol/L) and U46619 (0.003-0.1 mumol/L) reduced external diameter of the artery (about 2.0 mm) by 0.12 mm and 0.16 mm, respectively. Intra-arterial PGI2 (0.01-0.1 mumol/L) increased the diameter of the artery (by 0.08 mm) and reduced blood pressure of the support dog (by 23 mm Hg), but did not significantly (p greater than 0.05) reduce the vasoconstrictor effects of either 5-HT (0.3 mumol/L) or U46619 (0.1 mumol/L) infused simultaneously. Indomethacin (5 mg/kg i.v.) doubled the direct dilator effect of PGI2, and increased the sensitivity of the artery to 5-HT (by 11.5-fold) and to U46619 (by 2.8-fold). After indomethacin infusion, intra-arterial PGI2 (0.1 mumol/L) reduced the constriction induced by continuous infusion of 5-HT or U46619. These data suggest that PGI2 may be of limited usefulness in preventing constriction of large coronary vessels because it causes hypotension. However, endogenous PGI2 produced by the coronary vessels or pericardium may modulate the influence of coronary vasoconstrictors, and these tissues are therefore potential targets for PGI2-releasing drugs.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004347:Drug Interactions; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014666:Vasomotor System / Q000187:drug effects
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011464:Epoprostenol; D007213:Indomethacin