Endothelium-dependent effects of platelet-activating factor in the coronary circulation.

In experiments on anesthetized dogs, the effect of intracoronary administration of different doses of platelet-activating factor (PAF) has been investigated. One of the branches of the left coronary artery was catheterized via the main carotid artery. The coronary artery was autoperfused with blood from the subclavian artery. Intracoronary administration of small doses of PAF (100 and 200 ng/kg) caused a dose-dependent decrease in coronary resistance (CR) and an increase in coronary blood flow (CF). When 200 ng/kg of PAF was used, these changes were 30 and 34% vs. control, respectively. Dose increase to 300 ng/kg led to a biphasic reaction. Intracoronary administration of larger PAF doses produced opposite effects, i.e., increase in CR and decrease in CF. Chemical de-endothelialization by saponin (5 mg/5 ml, 1.5-2 min) transformed coronary dilation to small doses of PAF to constriction. The CR rose from 2.8 +/- 0.3 to 5.6 +/- 0.9 mm Hg/ml/min (p < 0.01) and CF dropped two-fold. The PAF receptor antagonists BN 52021 (6 mg/kg) and WEB 2086 (3 mg/kg) completely abolished PAF-induced coronary reactions. Hence, PAF-induced vasodilation of the canine coronary circulation is endothelium dependent.