title: Endothelium-dependent effects of halothane, enflurane, and isoflurane on isolated rat aortic vascular rings.
abstract: To determine the endothelium-dependent vascular effects of halothane, enflurane, and isoflurane, isometric tension was recorded in isolated ring preparations of rat thoracic aorta suspended in Kreb's buffer and aerated with 95% O2/5% CO2. One set of the rings had intact endothelium and the other set of the rings had the endothelium mechanically denuded. The rings were precontracted with phenylephrine (1 x 10(-6) M). Halothane, enflurane, or isoflurane gas was bubbled through the baths at increasing concentrations (0.5-5.0%) in preparations with and without indomethacin (28 microM). Endothelium-intact rings demonstrated significant (P less than 0.05) vasoconstriction at low concentrations of both isoflurane and enflurane followed by vasodilation at higher concentrations. Halothane also induced vasoconstriction in some rings, but its mean effect was not significantly different from control. After discontinuation of the anesthetic gas, endothelium-intact rings demonstrated a rebound vasoconstriction above previous maximal levels for all three anesthetics. When indomethacin was added to the baths, the vasoconstriction was potentiated and was statistically significant for all three anesthetics. These results suggest that at low concentrations, enflurane and isoflurane cause vasoconstriction through inhibition of basal EDRF production and/or stimulation of the release of an endothelium-derived constricting factor. At higher anesthetic concentrations, a direct vasodilating effect of the anesthetic predominates. The potentiation of vasoconstriction in the presence of indomethacin suggests that these volatile anesthetics stimulate the release of a vasodilating prostanoid from endothelium.
authors.affiliation: Department of Anesthesiology, University of Virginia School of Medicine, Charlottesville 22908.
authors.forename: D J
authors.initials: DJ
authors.lastname: Stone
authors.forename: R A
authors.initials: RA
authors.lastname: Johns
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004737:Enflurane / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D004737:Enflurane; D007530:Isoflurane; D006221:Halothane; D007213:Indomethacin