title: Halothane inhibits endothelium-dependent relaxation elicited by acetylcholine in human isolated pulmonary arteries.
abstract: This study examined whether a clinically relevant concentration of the volatile anaesthetic halothane modifies the endothelium-dependent relaxation produced by acetylcholine (3 nM-10 microM), histamine (1 pM-0.1 microM) and anti-human immunoglobulin E (1:1000) in human isolated pulmonary arteries submaximally precontracted with noradrenaline. An inhibitor of nitric oxide formation, N(G)-nitro-L-arginine (100 microM), attenuated acetylcholine-induced relaxation but failed to inhibit histamine- and anti-human immunoglobulin E-induced relaxation. Indomethacin (2.8 microM, a cyclooxygenase inhibitor) preferentially reduced the relaxation to histamine and anti-human IgE. Halothane (2%) significantly attenuated the relaxation to acetylcholine but had no significant effect on the relaxation elicited by histamine and anti-human IgE. Halothane (2%) enhanced the basal release of prostaglandin I2 by human pulmonary arteries (control 0.31 +/- 0.04 ng mg(-1); treated tissues 0.50 +/- 0.06 ng mg(-1); n = 5; P < 0.05). Halothane (2%) did not alter the responsiveness and sensitivity of preparations to relaxants acting through activation of adenylyl cyclase (forskolin) or guanylyl cyclase (sodium nitroprusside) or by the opening of K(ATP) channels (cromakalim). In conclusion, halothane inhibits the endothelium-dependent relaxation of human pulmonary arteries to acetylcholine by interfering with the nitric oxide pathway at a site before activation of soluble guanylyl cyclase in vascular smooth muscle.
authors.affiliation: Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario, Universitat de Valencia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Higueras
authors.forename: B
authors.initials: B
authors.lastname: Sarría
authors.forename: J L
authors.initials: JL
authors.lastname: Ortiz
authors.forename: J
authors.initials: J
authors.lastname: Cortijo
authors.forename: A
authors.initials: A
authors.lastname: Maruenda
authors.forename: M
authors.initials: M
authors.lastname: Barberá
authors.forename: E J
authors.initials: EJ
authors.lastname: Morcillo
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000262:Adenylyl Cyclases; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D019806:Cromakalim; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects*; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D066298:In Vitro Techniques; D009599:Nitroprusside / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors*
chemical_list: D018685:Anesthetics, Inhalation; D001578:Benzopyrans; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D009599:Nitroprusside; D005576:Colforsin; D007073:Immunoglobulin E; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D000109:Acetylcholine; D006221:Halothane