Potassium channels in the cardiovascular system.
In vitro and in vivo studies suggest that opening of ATP-sensitive potassium channels following ischaemia enhances recovery of myocardial contraction, dilates blood vessels and has an antiarrhythmic effect. Different sulphonylurea compounds that block the ATP-sensitive potassium channels exert different effects on cardiac functions. Glibenclamide decrease, arrhythmogenesis during acute myocardial infarction in rats and reduces strophanthin cardiotoxicity in rabbits. Other sulphonylurea compounds, but not glibenclamide, increase arterial blood pressure and myocardial contractility. These effects may be partly secondary to blockade of ATP-sensitive potassium channels and partly due to independent cardiac and extracardiac actions. Glimepiride may have a more advantageous cardiovascular effect than glibenclamide. The studies suggest the hypothesis that deleterious cardiovascular effects of some hypoglycaemic sulphonylurea drugs may contribute to the high cardiovascular mortality rate in diabetes mellitus. An observational study suggested glibenclamide decreased the incidence of fatal myocardial infarction and development of ventricular fibrillation in patients suffering from acute myocardial infarction. Glibenclamide may also decrease the incidence of ventricular ectopic beats in digitalized patients compared with other sulphonylurea compounds. The studies suggested the survival of subjects treated with glibenclamide, insulin, or diet alone after the first attack of angina pectoris or after first acute myocardial infarction may be longer compared with those on other sulphonylurea therapies. Further large scale prospective, randomised studies are needed to determine whether the reported effects can be verified and are sufficiently large to affect clinical prescribing.
National Institute of Cardiology, Research Department, Budapest, Hungary.
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Pogátsa
D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology / Q000517:prevention & control; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000503:physiopathology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D013328:Strophanthins / Q000037:antagonists & inhibitors / Q000633:toxicity; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D014693:Ventricular Fibrillation / Q000517:prevention & control
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D013328:Strophanthins; D013453:Sulfonylurea Compounds; D000255:Adenosine Triphosphate; D005905:Glyburide