title: Effects of glibenclamide on blood pressure and cardiovascular responsiveness in non-insulin dependent diabetes mellitus.
abstract: OBJECTIVE
  To compare the effects of chronic glibenclamide therapy and placebo on blood pressure and cardiovascular responsiveness in patients with non-insulin-dependent diabetes.
  
  
  METHODS
  Fourteen patients with non-insulin-dependent diabetes mellitus, seven of whom were receiving angiotensin converting enzyme inhibitor therapy, received glibenclamide or placebo for 1 month in a double-blind, randomized crossover study. At the end of each treatment period patients attended for studies of forearm vascular responsiveness to intra-brachial arterial infusions of angiotensin II, acetylcholine, sodium nitroprusside and noradrenaline, responses of blood pressure to intravenous infusions of noradrenaline and angiotensin II and 24 h ambulatory blood pressure monitoring.
  
  
  RESULTS
  Administration of glibenclamide produced significantly better glycaemic control than placebo (fasting blood glucose level 8.5 +/- 2.4 versus 13.5 +/- 4.5 mmol/l, P < 0.001) and plasma insulin levels were significantly higher during glibenclamide treatment than they were with placebo (12.9 +/- 4.4 versus 9.2 +/- 4.1 mU/l, P < 0.05). Body weights at the ends of the glibenclamide treatment and placebo phases were similar (92.1 +/- 14.3 versus 91.1 +/- 14.3 kg, P = 0.085). Night-time systolic blood pressures were significantly higher during glibenclamide treatment than they were with placebo (128 +/- 17 versus 118 +/- 10 mmHg, P < 0.05) due to there being a smaller day-night difference in systolic blood pressure during glibenclamide treatment that appeared to occur mainly in patients receiving angiotensin converting enzyme inhibitors. Responses of diastolic blood pressure to intravenous infusion of angiotensin II and forearm vascular responses to intra-brachial arterial infusion of angiotensin II were significantly greater during glibenclamide treatment than they were with placebo (P < 0.05). However, the enhancement of forearm vascular responses during glibenclamide treatment appeared to be restricted to patients receiving angiotensin converting enzyme inhibitors. Responses of blood pressure to intravenous infusion of noradrenaline and forearm vascular responses to infusions of noradrenaline, acetylcholine and nitroprusside did not differ between glibenclamide treatment and placebo; neither did basal forearm vascular resistance.
  
  
  CONCLUSIONS
  Glibenclamide therapy is associated with greater responses of blood pressure and forearm vascular responses to infusion of angiotensin and higher nocturnal blood pressures. This effect appears to be influenced by concomitant angiotensin converting enzyme inhibition.
authors.affiliation: Department of Clinical Pharmacology, UNSW, St George Hospital, Kogarah, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.forename: D
authors.initials: D
authors.lastname: Abbott
authors.forename: L
authors.initials: L
authors.lastname: Morfis
authors.forename: P
authors.initials: P
authors.lastname: Manwaring
authors.forename: T
authors.initials: T
authors.lastname: Diamond
authors.forename: L G
authors.initials: LG
authors.lastname: Howes
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005542:Forearm / Q000098:blood supply; D005905:Glyburide / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009599:Nitroprusside; D000109:Acetylcholine; D005905:Glyburide; D009638:Norepinephrine