Possible involvement of endothelin in thromboxane A2 receptor agonist (U-46619)-induced angina in the rat

The thromboxane A2 receptor agonist, U-46619 ((5Z,9α,11α,13E,15(S))-9,11-(methanoepoxy)prosta-5,13-dien-1-oic acid) (10 μg/kg), induced a typical ischemic change (ST elevation) in the electrocardiogram on intracoronary arterial administration in the rat. The elevation of the ST segment induced by U-46619 was significantly reduced by pretreatment with anti-endothelin-1 rabbit serum. The plasma concentration of endothelin-1 dose dependently increased at the time of ST segment elevation after U-46619. These results indicate that endogenous endothelin-1 partly contributes to coronary spasmodic angina induced by thromboxane A2 in rats.