VASODILATOR AND CONSTRICTOR ACTIONS OF PLATELET-ACTIVATING-FACTOR IN THE ISOLATED MICROPERFUSED AFFERENT ARTERIOLE OF THE RABBIT KIDNEY - ROLE OF ENDOTHELIUM-DERIVED RELAXING FACTOR NITRIC-OXIDE AND CYCLOOXYGENASE PRODUCTS

It has been suggested that platelet-activating factor (PAF) plays a pr ominent role in the control of glomerular hemodynamics in various phys iological and pathological conditions. We examined the direct effect o f PAF on rabbit glomerular afferent arterioles (Af-Arts) microperfused in vitro and tested whether endothelium-derived relaxing factor/nitri c oxide (EDNO) and cyclooxygenase products are involved in its actions . In nanomolar concentrations PAF caused dose-dependent constriction o f Af-Arts, with the maximum constriction being 34+/-10% at 4x10(-8) M (n = 9, P < 0.001).The constriction was blunted by cyclooxygenase inhi bition (11+/-6%, n = 7, P < 0.05) but augmented by EDNO inhibition (76 +/-14%, n = 8, P < 0.005). To study a possible vasodilator effect of P AF, Af-Arts were preconstricted with norepinephrine and increasing con centrations of PAF added to the lumen. At picomolar concentrations (lo wer than those that caused constriction), PAF produced dose-dependent vasodilation that was unaffected by cyclooxygenase inhibition but was abolished by EDNO synthesis inhibition. Both PAF-induced constriction and dilation of Af-Arts were blocked by a PAF receptor antagonist. Thi s study demonstrates that PAF has a receptor-mediated biphasic effect on rabbit Af-Arts, dilating them at low concentrations while constrict ing them at higher concentrations. Our results suggest that PAF's vaso dilator action may be due to production of EDNO, while its constrictor action is mediated at least in part through cyclooxygenase products.