ROLE OF ENDOGENOUS NITRIC-OXIDE ON PAF-INDUCED VASCULAR AND RESPIRATORY EFFECTS

THE role of endogenous nitric oxide (NO) on vascular and respiratory s mooth muscle basal tone was evaluated in six anaesthetized, paralysed, mechanically ventilated pigs. The involvement of endogenous NO in PAF -induced shock and airway hyperresponsiveness was also studied. PAF (5 0 ng/kg, i.v.) was administered before and after pretreatment with N-G -nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.v.), an NO synthes is inhibitor. PAF was also administered to three of these pigs after i ndomethacin infusion (3 mg/kg, i.v.). in normal pigs, L-NAME Increased systemic and pulmonary vascular resistances, caused pulmonary hyperte nsion and reduced cardiac output and stroke volume. The pulmonary vasc ular responses were correlated with the increase in static and dynamic lung elastances, without changing lung resistance. Inhibition of NO s ynthesis enhanced the PAF-dependent increase in total, intrinsic and v iscoelastic lung resistances, without affecting, lung elastances or ca rdiac activity. The systemic hypotensive effect of PAF was not abolish ed by pretreatment with L-NAME or indomethacin. This indicates that sy stemic hypotension is not correlated with the release of endogenous NO or prostacyclines. Indomethacin completely abolished the PAF-dependen t respiratory effects.