PLATELET-ACTIVATING FACTOR-INDUCED LOSS OF VASCULAR RESPONSIVENESS TONORADRENALINE IN PITHED RATS - INVOLVEMENT OF NITRIC-OXIDE

The role of nitric oxide and cyclo-oxygenase products in the platelet- activating factor (PAF)-induced hyporesponsiveness to noradrenaline wa s investigated in pithed rats. Infusion of PAF (30 ng/kg/min) for 60 m in reduced the mean arterial blood pressure and impaired the presser r esponses to noradrenaline (10 ng/kg, 100 ng/kg, 1 mu g/kg). Administra tion of N-G-monomethyl-L-arginine (L-NMMA, 30 mg/kg) restored the redu ced MABP and the impaired responses to their original levels. Indometh acin (5 mg/kg) had no significant effect on the PAF-induced hyporespon siveness. Administration of 30 mg/kg L-NMMA caused hypertension in the PAF vehicle-treated animals and reduced the presser response to 1 mu g/kg noradrenaline. Administration of 3 mg/kg L-NMMA had no significan t effect on the responsiveness to noradrenaline. These results suggest that nitric oxide contributes to the PAF-induced hyporesponsiveness t o noradrenaline and that cyclo-oxygenase products do not play a major role in this hyporesponsiveness.