title: Hypercapnia-induced cerebral and ocular vasodilation is not altered by glibenclamide in humans.
abstract: Carbon dioxide is an important regulator of vascular tone. Glibenclamide, an inhibitor of ATP-sensitive potassium channel (K(ATP)) activation, significantly blunts vasodilation in response to hypercapnic acidosis in animals. We investigated whether glibenclamide also alters the cerebral and ocular vasodilator response to hypercapnia in humans. Ten healthy male subjects were studied in a controlled, randomized, double-blind two-way crossover study under normoxic and hypercapnic conditions. Glibenclamide (5 mg po) or insulin (0.3 mU. kg(-1). min(-1) iv) were administered with glucose to achieve comparable plasma insulin levels. In control experiments, five healthy volunteers received glibenclamide (5 mg) or nicorandil (40 mg) or glibenclamide and nicorandil in a randomized, three-way crossover study. Mean blood flow velocity and resistive index in the middle cerebral artery (MCA) and in the ophthalmic artery (OA) were measured with Doppler sonography. Pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation. Forearm blood flow was measured with venous occlusion plethysmography. Hypercapnia increased ocular fundus pulsation amplitude by +18.2-22.3% (P < 0. 001) and mean flow velocity in the MCA by +27.4-33.3% (P < 0.001), but not in the OA (2.1-6.5%, P = 0.2). Forearm blood flow increased by 78.2% vs. baseline (P = 0.041) after nicorandil administration. Glibenclamide did not alter hypercapnia-induced changes in cerebral or ocular hemodynamics and did not affect systemic hemodynamics or forearm blood flow but significantly increased glucose utilization and blunted the nicorandil-induced vasodilation in the forearm. This suggests that hypercapnia-induced changes in the vascular beds under study are not mediated by activation of K(ATP) channels in humans.
authors.affiliation: Department of Clinical Pharmacology, University of Vienna School of Medicine, A-1090 Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Bayerle-Eder
authors.forename: M
authors.initials: M
authors.lastname: Wolzt
authors.forename: E
authors.initials: E
authors.lastname: Polska
authors.forename: H
authors.initials: H
authors.lastname: Langenberger
authors.forename: J
authors.initials: J
authors.lastname: Pleiner
authors.forename: D
authors.initials: D
authors.lastname: Teherani
authors.forename: G
authors.initials: G
authors.lastname: Rainer
authors.forename: K
authors.initials: K
authors.lastname: Polak
authors.forename: H G
authors.initials: HG
authors.lastname: Eichler
authors.forename: L
authors.initials: L
authors.lastname: Schmetterer
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000280:Administration, Inhalation; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply; D001923:Brain Chemistry / Q000502:physiology; D002245:Carbon Dioxide / Q000008:administration & dosage; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D005123:Eye / Q000098:blood supply; D005542:Forearm / Q000098:blood supply; D005905:Glyburide / Q000008:administration & dosage*; D006339:Heart Rate; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D020108:Nicorandil / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D015221:Potassium Channels; D014665:Vasodilator Agents; D002245:Carbon Dioxide; D020108:Nicorandil; D000255:Adenosine Triphosphate; D005905:Glyburide