U-46619-induced ischaemic electrocardiographic changes in rats: preventive effects of prostacyclin and nitroglycerin

The anti-anginal effect of nitroglycerin and prostacyclin was examined using, as an index, the ischaemic electrocardiogram (ECG) change (ST elevation) induced by intracoronary arterial injection of 9,11-dideoxy-11 alpha,9 alpha-epoxymethano-PGF2 alpha (U-46619), a stable thromboxane A2 agonist, in anaesthetized rats. The ST elevation induced by U-46619 (5-20 micrograms kg-1, i.c.a.) was dose-dependent and reproducible. U-46619-induced ST elevation was markedly prevented by the pretreatment of intravenous administration of prostacyclin (0.01 micrograms kg-1), and to a lesser extent by nitroglycerin (0.3 mg kg-1). Simultaneously, platelet count decreased significantly in the coronary arterial blood which indicated that platelet aggregation was enhanced by U-46619. The decrease of platelet count in coronary arterial blood at the time of ST elevation was significantly suppressed by prostacyclin (0.1 microgram kg-1, i.v.), but not by nitroglycerin (0.3 mg kg-1, i.v.). These results suggest that the ST elevation induced by intracoronary arterial injection of U-46619 may be derived from spasm of coronary artery and platelet aggregation in the intracoronary artery in rats.