Background: Endothelium-derived nitric oxide causes vasodilation in part by increasing the dilator activity of other endothelium-derived mediators, including prostacyclin and a K+ATP channel-dependent hyperpolarizing factor. Although previous studies have proposed that isoflurane (ISO) depresses endothelium-dcpendent vasorelaxation by inhibiting endothelium-derived nitric oxide activity, the effects of ISO on the interactions among endothelium-derived dilators have not been characterized. The aim of this study was to determine the mechanisms underlying the inhibitory effect of ISO on endothelium-dependent relaxation in canine pulmonary arteries. Specifically, the goal was to assess the effects of ISO on the individual actions and on the synergistic interactions of these endothelium-derived mediators. Methods: Canine pulmonary arterial rings were suspended for isometric tension recording. The effects of 1 minimum alveolar concentration ISO (0.4 HIM) on vasorelaxation responses to bradyldnin, A23187, acetylcholine, cromakalim, and SIN-1 were assessed in phenylephrine-precontracted rings with and without pretreatment with a nitric oxide synthase inhibitor (Nω-nitro-L-arginine methyl ester; L-NAME), a cyclooxygenase inhibitor (indomethacin), or a K+ATP channel inhibitor (glybenclamide). Results: Isofluane attenuated pulmonary vasorelaxation induced by bradykinin, A23187, and cromakalim but had no effect on relaxation induced by acetylcholine or SIN-1. Neither the nitric oxide-mediated nor the prostacyclin-mediated com-ponents of relaxation induced by bradykinin and A23187 were altered by ISO. However, ISO abolished the K+ATP-mediated component of relaxation and the K+ATP-dependent synergistic interaction between nitric oxide and prostacyclin. Conclusions: These results suggest that ISO selectively attenuates endothelium-dependent relaxation in canine pulmonary arteries. It exerts its inhibitory effect by interfering with a synergistic interaction between nitric oxide and prostacyclin, possibly via an effect on K+ATP channels.
- Anesthetics, volatile: Isoflurane
- Lung(s): Circulation
- Pharmacology, agonists: Acetylcholine; bradykinin; calcium ionophore (a23187); cromakalim; sin-1
ASJC Scopus subject areas
- Anesthesiology and Pain Medicine