Platelet-activating factor-induced loss of vascular responsiveness to noradrenaline 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 was investigated in pithed rats. Infusion of PAF (30 ng/kg/min) for 60 min reduced the mean arterial blood pressure and impaired the pressor responses to noradrenaline (10 ng/kg, 100 ng/kg, 1 microgram/kg). Administration of NG-monomethyl-L-arginine (L-NMMA, 30 mg/kg) restored the reduced MABP and the impaired responses to their original levels. Indomethacin (5 mg/kg) had no significant effect on the PAF-induced hyporesponsiveness. Administration of 30 mg/kg L-NMMA caused hypertension in the PAF vehicle-treated animals and reduced the pressor response to 1 microgram/kg noradrenaline. Administration of 3 mg/kg L-NMMA had no significant effect on the responsiveness to noradrenaline. These results suggest that nitric oxide contributes to the PAF-induced hyporesponsiveness to noradrenaline and that cyclo-oxygenase products do not play a major role in this hyporesponsiveness.
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003655:Decerebrate State; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014666:Vasomotor System / Q000187:drug effects*; D019323:omega-N-Methylarginine
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D010972:Platelet Activating Factor; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D009638:Norepinephrine; D007213:Indomethacin