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.
Yamamoto
T
T
Department of Pharmacology, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Kikuta
C
C
Hosoki
K
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000704:Analysis of Variance; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000187:drug effects*; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000517:prevention & control*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000633:toxicity*
D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011464:Epoprostenol; D005996:Nitroglycerin