ISOFLURANE INHIBITS ENDOTHELIUM-MEDIATED NITRIC-OXIDE RELAXING PATHWAYS IN THE ISOLATED-PERFUSED RABBIT LUNG

Purpose: The role of volatile anaesthetics on nitric oxide (NO)-depend ent relaxation is unclear in the pulmonary circulation. We examined th e effects of isoflurane on NO-dependent relaxation in isolated perfuse d rabbit lungs. Methods: Eighteen rabbit lungs were perfused in a cons tant-flow recirculation manner. In study 1 (n=12), acetylcholine (ACh, 4 x 10(-10) - 10(-8) M) or nitroglycerine (NTG, 6 x 10(-10) - 10(-8) M) was cumulatively injected into the pulmonary artery in the absence or presence of isoflurane (1, 2 MAC). In study 2 (n=6), ACh was inject ed as in study 1 in the presence or absence of N omega-nitro-L-arginin e methyl ester (L-NAME, 100 mu M), an NO synthesis blocker. In ail exp eriments, indomethacin was administered to prevent formation of vasoac tive prostanoid metabolites, and the pulmonary vessels were preconstri cted with prostaglandin F2 alpha (PGF2 alpha) infused before ACh or NT G injection. The ACh- or NTG-induced relaxation was expressed as % dec rease in PGF2 alpha preconstriction. Results: Isoflurane at 2 MAC atte nuated the dose-dependent relaxation to ACh at doses of 4 x 10(-9)M an d 4 x 10(-8) M from 27.8 +/- 4.3% and 38.8 +/- 5.3% to 17.0 +/- 3.5% a nd 25.5 +/- 4.9%, respectively (P < 0.05). Isoflurane did not change t he dose-dependent relaxation to NTG and L-NAME abolished the ACh-induc ed relaxation. Conclusion: Isoflurane inhibited NO-dependent relaxatio n in the pulmonary circulation at a site distal to the endothelial cel l receptor-mediated responses but proximal to guanylate cyclase activa tion of vascular smooth muscle. Acetylcholine-induced relaxation in is olated perfused rabbit lungs was regulated primarily by NO.