Different potency of endothelium-derived relaxing factors against thromboxane, endothelin, and potassium chloride in intramyocardial porcine coronary arteries.
Endothelium-derived relaxing factors (EDRFs) and prostacyclin (PGI2) released from endothelial cells are potent vasodilators; endothelin-1 and thromboxane A2 may be their physiological antagonists. Interactions between these vasodilators and vasoconstrictors were studied in isolated intramyocardial porcine coronary arteries suspended in myographs for isometric tension recording. Endothelium-dependent relaxations to bradykinin and serotonin were reduced to a similar extent in arteries contracted with endothelin-1 and KCl as compared to those contracted with the thromboxane analog U 46619 (p less than 0.05; n = 5-6). In contrast, relaxations to the nitric oxide donor SIN-1 were comparable. PGI2 was most potent in arteries exposed to U 46619, while its effects were inhibited in the presence of endothelin-1 or acetylcholine and prevented by KCl (p less than 0.05-0.0001; n = 5). At high concentrations PGI2 evoked contractions in arteries contracted with endothelin-1, acetylcholine, or KCl, but not in those with U 46619, which were prevented by the thromboxane receptor antagonist SQ 30741 (p less than 0.05; n = 5), indicating that PGI2 is a partial agonist for the thromboxane receptor. Thus, in intramyocardial porcine coronary arteries, contractile agonists differently interact with the release and action of EDRFs and PGI2. Both are most effective against contractions induced by thromboxane. In contrast, endothelin-1 and particularly KCl reduce the potency of these endogenous vasodilator systems.
Noll
G
G
Department of Research, University Hospital, Basel, Switzerland.
Bühler
F R
FR
Yang
Z
Z
Lüscher
T F
TF
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects; D016232:Endothelins / Q000037:antagonists & inhibitors*; D011464:Epoprostenol / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013931:Thromboxanes / Q000037:antagonists & inhibitors*
D016232:Endothelins; D011450:Prostaglandin Endoperoxides, Synthetic; D013931:Thromboxanes; C054215:SQ 30741; D009569:Nitric Oxide; D012701:Serotonin; D013928:Thromboxane A2; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011464:Epoprostenol; D001920:Bradykinin