THE ACUTE INCREASES IN VASOMOTOR TONE AND BLOOD-PRESSURE INDUCED BY CAROTID-ARTERY OCCLUSION ARE MODULATED BY PLATELET-ACTIVATING-FACTOR (PAF) INDEPENDENTLY OF NITRIC-OXIDE RELEASE

The purpose of the present study was to investigate the involvement of nitric oxide (NO) in the modulatory role of platelet-activating facto r (PAF, xadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). a vasoactiv e phospholipid mediator synthesized by endothelial cells, on the vascu lar tone and arterial blood pressure. In pentobarbitone-anaesthetized rabbits, unloading of the carotid sinus baroreceptors by a bilateral c arotid artery occlusion elicited a reflex rise in systemic vascular re sistance, which was markedly potentiated by pretreating the animals wi th the PAF receptor antagonist WEB 2086 ([3-4-(2-chlorphenyl-)-9-methy l-6H-thieno-3,2-f-1, olo-4,3-alpha-1,4-diazepin-2-yl-(4-morpholinyl)-1 - propanone]; 5 mg/kg, i.v.). In contrast, the inhibition of the biosy nthesis of NO via NO synthase using N-omega-nitro-L-arginine methyl es ter (L-NAME) neither affected the systemic vasoconstriction induced by carotid artery occlusion nor modified the potentiating effect of WEB 2086. The haemodynamic alterations induced by L-NAME administration we re corrected by continuous infusions of the directly-acting vasodilato rs sodium nitroprusside or diazoxide. The results of the present study confirm previous studies from our roup suggesting the involvement of PAF in a negative feedback mechanism effective in the local regulation of vasomotor tone in anaesthetized rabbits, but exclude the participa tion of NO in this process. (C) 1997 Elsevier Science B.V.