title: Acute effects of oral glibenclamide on blood pressure and forearm vascular resistance in diabetics.
abstract: 1. To determine the effects of an acute oral dose of glibenclamide on blood pressure (BP), basal forearm vascular resistance (FVR) and FVR responses to the K+ATP channel activating vasodilator diazoxide, a placebo-controlled, double-blind cross-over study was performed in eight male volunteers with non-insulin-dependent diabetes mellitus. 2. Changes in vascular responses to progressively increasing concentrations of diazoxide (3.75-30 mg/kg per min) and noradrenaline (25-100 ng/kg per min) were measured by venous occlusion plethysmography. 3. Glibenclamide significantly lowered plasma glucose levels compared with placebo (P < 0.02) and attenuated the decrease in FVR (P < 0.05) and the decrease in systolic BP (P < 0.05) that followed a meal. However, vasodilator responses to diazoxide were potentiated by the administration of oral glibenclamide (P < 0.01). 4. Acute administration of oral glibenclamide attenuates the normal decrease in FVR and systolic BP that follows a meal and potentiates rather than inhibits forearm vasodilator responses to intra-arterial diazoxide, probably via indirect humoral effects. These results suggest that glibenclamide has direct or indirect vasoconstrictor effects that antagonize the normal increase in forearm blood flow that follows a meal and that the inhibition of vascular K+ATP channels following acute oral glibenclamide administration is clinically insignificant compared with other indirect vascular effects of the drug.
authors.affiliation: Department of Clinical Pharmacology, University of New South Wales, Kogarah, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Sundaresan
authors.forename: D
authors.initials: D
authors.lastname: Lykos
authors.forename: A
authors.initials: A
authors.lastname: Daher
authors.forename: R
authors.initials: R
authors.lastname: Morris
authors.forename: T
authors.initials: T
authors.lastname: Diamond
authors.forename: L G
authors.initials: LG
authors.lastname: Howes
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003981:Diazoxide / Q000494:pharmacology; D004311:Double-Blind Method; D005542:Forearm / Q000098:blood supply; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D015221:Potassium Channels; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000255:Adenosine Triphosphate; D003981:Diazoxide; D005905:Glyburide; D009638:Norepinephrine