NITRIC-OXIDE MEDIATES THE INHIBITORY-ACTION OF PLATELET-ACTIVATING-FACTOR ON ANGIOTENSIN-II-INDUCED RENAL VASOCONSTRICTION, IN-VIVO

The objective of our study was to determine the mechanism(s) involved in the inhibitory effect of platelet-activating factor on renal vascul ar reactivity, in vivo. Bolus injections of vasoconstrictor agonists w ere administered into the renal circulation of pentobarbital anestheti zed male Wistar rats at a dose to cause a transient 45 to 50% decrease in renal blood flow, Intrarenal infusion of platelet-activating facto r (PAF) at 2.5 ng/min/kg attenuated the vasoconstrictor response to an giotensin II by 66%, a significantly smaller reduction of 35% for nore pinephrine mediated vasoconstriction, 22% for vasopressin-mediated vas oconstriction and no alteration of KCl-mediated vasoconstriction. The preferential inhibitory effect of platelet-activating factor on angiot ensin II-mediated renal vasoconstriction was mimicked by the intrarena l infusion of either 0.2 to 5 mu g/min/kg methacholine (endothelium-de pendent vasodilator) or 2 mu g/ min/kg sodium nitroprusside (nitric ox ide donor). After inhibition of nitric oxide synthesis with N-G-monome thyl-L-arginine, intrarenal infusion of PAF or methacholine reduced an giotensin it-mediated renal vasoconstriction significantly less than t hat observed in the absence of N-G-monomethyl-L-arginine. Therefore, t his study provides evidence that the shared ability of platelet-activa ting factor and methacholine to selectively reduce angiotensin II-medi ated renal vasoconstriction involves endothelium-derived nitric oxide.