Endothelium-derived relaxing factor is not responsible for inhibition of hypoxic pulmonary vasoconstriction by inhalational anesthetics.
Inhalational anesthetics inhibit hypoxic pulmonary vasoconstriction (HPV). One mechanism suggested for this action is stimulation of release of endothelium-derived relaxing factor. The present study has tested this hypothesis. These studies were performed in 66 ventilated and perfused isolated rat lungs. There were three study protocols. Study 1 examined the effect of HPV of the inhibition of soluble guanylate cyclase by methylene blue (MB). In the presence or absence of MB, the lungs constricted to hypoxia with pulmonary artery pressure increases of 8.6 +/- 0.2 cmH2O and 11.5 +/- 0.4 cmH2O, respectively, and halothane, enflurane, and isoflurane caused a reversible 50% decrease in the pulmonary pressor response, but acetylcholine (ACh) was vasodilatory in the saline group and vasoconstrictor in the MB group. In Study II a dose-response curve was established for the potent stimulator (Sin 1) of the enzyme guanylate cyclase. In the presence of MB the dose-response curve for Sin 1 was shifted to the right with an increase in the ED50 for Sin 1 from 44 microM for the control to 85 microM for the MB group. In Study III, baseline pulmonary artery pressure was increased with U46619, and the hypoxic pressor response was increased (28.9 +/- 2.5 cmH2O), but halothane again caused a 50% decrease (11.0 +/- 1.8 cmH2O) in the response to hypoxia. In summary, when soluble guanylate cyclase activity is inhibited by MB, the inhibition of hypoxic pulmonary vasoconstriction by halothane, isoflurane, or enflurane was unaltered, and release of endothelium-derived relaxing factor (EDRF) is therefore not an essential mechanism underlying this action.
Marshall
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Department of Anesthesia, University of Pennsylvania School of Medicine, Philadelphia 19104-4283.
Marshall
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D000818:Animals; D004737:Enflurane / Q000494:pharmacology*; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D009569:Nitric Oxide; D004737:Enflurane; D007530:Isoflurane; D006221:Halothane