title: Tolerance to glyceryl trinitrate in isolated human internal mammary arteries.
abstract: The purpose of this study was to examine the vascular reactivity of segments of internal mammary artery removed from patients undergoing coronary artery bypass operations. Responses to relaxant and contractile agents were compared in arteries removed from patients who had or had not been treated with glyceryl trinitrate after admission to the hospital until operation. Segments of mammary artery were removed from 13 patients who underwent coronary artery bypass grafting. Endothelium-containing rings of artery, 3 to 5 mm long, were suspended in physiologic saline solution in 20 ml organ baths. Responses to the endothelium-dependent relaxant acetylcholine and the endothelium-independent relaxants glyceryl trinitrate and sodium nitroprusside were compared. In addition, contractile responses to phenylephrine and 9,11-dideoxy-9 alpha,11 alpha-methanoepoxy prostaglandin F2 alpha (U46619) were examined. Glyceryl trinitrate-induced relaxation was significantly impaired in mammary artery segments from patients treated with that nitrate before operation; the responses to acetylcholine and sodium nitroprusside were not affected. Previous treatment with glyceryl trinitrate also reduced the contractile responses to both phenylephrine and U46619. These studies indicate that treatment of patients with glyceryl trinitrate before operation induces significant tolerance to this agent in the mammary artery; however, there was no evidence of cross tolerance to sodium nitroprusside or the endothelium-dependent vasodilator acetylcholine. Glyceryl trinitrate may therefore not always be effective in dilating mammary artery grafts and sodium nitroprusside may be a more effective dilator of the internal mammary artery in patients who have been treated with glyceryl trinitrate before operation.
authors.affiliation: Department of Pharmacology, University of Melbourne, Australia.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Du
authors.forename: B F
authors.initials: BF
authors.lastname: Buxton
authors.forename: O L
authors.initials: OL
authors.lastname: Woodman
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D006801:Humans; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D011292:Premedication; D011450:Prostaglandin Endoperoxides, Synthetic / Q000008:administration & dosage / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D011450:Prostaglandin Endoperoxides, Synthetic; D009599:Nitroprusside; D010656:Phenylephrine; D005996:Nitroglycerin; D000109:Acetylcholine