Different potencies of endothelium-derived relaxing factors against thromboxane and endothelin-1 in coronary arteries: comparison with nitrovasodilator and calcium antagonists

The interaction of endothelium-derived relaxing factors such as nitric oxide (NO) and prostacyclin with vasoconstrictors such as endothelin-1 and thromboxane makes an important contribution to coronary vascular tone. The influence of contractile agonists on the potency of relaxing factors was studie...

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Veröffentlicht in:Coronary artery disease 1991-11, Vol.2 (9), p.1001-1008
Hauptverfasser: Ritz, Marc A, Lüscher, Thomas F
Format: Artikel
Sprache:eng
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Zusammenfassung:The interaction of endothelium-derived relaxing factors such as nitric oxide (NO) and prostacyclin with vasoconstrictors such as endothelin-1 and thromboxane makes an important contribution to coronary vascular tone. The influence of contractile agonists on the potency of relaxing factors was studied in porcine coronary arteries suspended in organ chambers for isometric tension recording. Endothelium-dependent relaxations to bradykinin or serotonin, relaxations to prostacyclin or the NO donor 3-morpholinosydnonimine (SIN-1) were measured after equipotent contractions to KCl, endothelin-1, or the thromboxane analogue U 46619. KCl markedly reduced the maximal response, but not the sensitivity to bradykinin as compared with endothelin-1 and particularly with U 46619. KCl severely blunted the maximal relaxation and sensitivity to serotonin as compared with U 46619. Endothelin-1 markedly reduced the maximal response, but not sensitivity to serotonin. Prostacyclin was similarly potent in arteries contracted with U 466199 or endothelin-1, but ineffective after KCl. The maximal response to SIN-1 did not differ, but the sensitivity was reduced with KCl as compared with endothelin-1 or U 46619. The potency of Ca antagonists verapamil, darodipine, and diltiazem was greatest with KCl, but smaller with U 46619 and particularly endothelin-1. Thus, in healthy coronary arteries, contractile antagonists markedly affect the potency of endogenous and therapeutic vasodilators. Endothelium-derived relaxing factors and SIN-1 were most effective against contractions to U 46619 and to a lesser extent to endothelin-1, but were markedly inhibited by KCl. In contrast, Ca antagonists were most effective against contractions by KCl. Hence, nitrovasodilators and Ca antagonists would be useful in states with an abnormal endothelium function.
ISSN:0954-6928
1473-5830