limaprost and Angina-Pectoris

Topics: Adenosine Diphosphate; Administration, Oral; Alprostadil; Angina Pectoris; Animals; Collagen; Drug Evaluation, Preclinical; Guinea Pigs; Heart; Humans; Platelet Aggregation; Prostaglandins E; Prostaglandins E, Synthetic; Rats; Structure-Activity Relationship; Vasodilation; Vasopressins

Effects of OP 1206 were studied on the cardiovascular system and platelet functions to assess OP 1206 as an antianginal agent. OP 1206 given orally at more than 100 micrograms/kg relieved vasopressin-induced ST depression of rat electrocardiogram (ECG), an animal model of angina pectoris, concomitant with slight hypotension. Intra-coronary injection of OP 1206 (1-100 ng/kg) in dogs resulted in a remarkable increase of coronary blood flow without any influence on heart rate, blood pressure, myocardial oxygen consumption and redox potential. Resistance in both large and small vessels of dog coronary artery was decreased by intravenous injection of OP 1206 (1-3 micrograms/kg). Platelet aggregation, adhesiveness, bleeding time, and thrombocytopenia induced by ADP and collagen infusion in guinea-pigs were inhibited by oral administration of OP 1206 at the same doses or doses less than those relieving vasopressin-induced ST depression of ECG. These results suggest that OP 1206 contributes to the improvement of cardiac imbalance between oxygen demand and supply, and suppression of thrombus formation in atherosclerotic heart.

Topics: Alprostadil; Angina Pectoris; Animals; Blood Platelets; Dogs; Electrocardiography; Female; Hemodynamics; Male; Myocardium; Oxygen Consumption; Platelet Adhesiveness; Platelet Aggregation; Prostaglandins E, Synthetic; Rats; Thrombocytopenia; Vascular Resistance