3--angeloyloxy-4--acetoxy-3--4--dihydroseselin and Disease-Models--Animal

A pyranocoumarin compound, 3'-angeloyloxy-4'-acetoxy-3',4'-dihydroseselin (Pd-Ia), isolated from Bai-Hua Qian-Hu, a Chinese medicine, is known to possess a Ca2+ channel antagonist action. We examined the effect of Pd-Ia on cardiohemodynamics and regional myocardial dysfunction after transient ischemia in anesthetized open-chest dogs. I.v. injections of Pd-Ia (0.1-3.0 mg/kg, n = 7) significantly and dose dependently increased coronary blood flow and decreased mean aortic pressure, maximal rate of rise in left ventricular pressure, rate pressure product and systemic vascular resistance, together with a slight increase in heart rate. Diltiazem (0.03-1.00 mg/kg, n = 6) showed effects on the cardiohemodynamics similar to those of Pd-Ia, except for a marked decrease in heart rate. The effects of Pd-Ia on mean aortic pressure and rate pressure product were approximately 10 times less potent than those of diltiazem. In the second experiment, the effect of a 30-min infusion of Pd-Ia (0.15 mg/kg/min) or vehicle on regional myocardial dysfunction was examined in 16 anesthetized dogs subjected to a 15-min occlusion of the left anterior descending coronary artery followed by a 3-h reperfusion. Infusion of Pd-Ia was started 15 min before coronary occlusion. The vehicle caused a decrease in percent segment shortening throughout the reperfusion period (n = 8). However, Pd-Ia at the dose that produced no significant changes in cardiohemodynamics resulted in a marked improvement in percent segment shortening of the ischemic and reperfused myocardium (n = 8, P < 0.05 vs. control group).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Calcium Channel Blockers; Coronary Circulation; Coumarins; Diltiazem; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Female; Hemodynamics; Injections, Intravenous; Male; Myocardial Ischemia; Vascular Resistance