Glibenclamide attenuates adenosine-induced bradycardia and coronary vasodilatation.
The effects of the ATP-sensitive K(+)-channel blocker glibenclamide on the cardiovascular responses to adenosine in dogs were determined. Adenosine (0.01-20 mumol/kg iv) caused coronary vasodilatation, arterial hypotension, and bradycardia in dogs with either combined beta-adrenergic and muscarinic receptor blockade or with bilateral cervical vagotomy plus beta-adrenergic receptor blockade. The 50% effective dose for adenosine-induced coronary dilatation was increased from 0.13 +/- 0.04 mumol/kg in the control state to 1.1 +/- 0.5 mumol/kg after 2 mg/kg of glibenclamide (P less than 0.001). Adenosine at 5 mumol/kg reduced heart rate by 19 +/- 5% from a baseline of 158 +/- 6 beats/min in five anesthetized dogs. After glibenclamide (10 mg/kg), this dose of adenosine failed to cause a significant change in heart rate. The arterial hypotensive effects of adenosine were also attenuated by glibenclamide. Thus glibenclamide inhibited adenosine-induced bradycardia, hypotension, and coronary dilatation. On the other hand, glibenclamide did not affect the reductions in heart rate caused by vagus nerve stimulation. The mechanism of this adenosine antagonism is not known but, in the case of bradycardia, it does not appear to involve any of the steps shared in common by both adenosine-induced and vagal responses of the sinoatrial node.
Belloni
F L
FL
Department of Physiology, New York Medical College, Valhalla 10595.
Hintze
T H
TH
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005905:Glyburide / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D012016:Reference Values; D014630:Vagus Nerve / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
D000241:Adenosine; D007545:Isoproterenol; D005905:Glyburide