Nicorandil protects ATP-sensitive potassium channels against oxidation-induced dysfunction in cardiomyocytes of aging rats.
ATP-sensitive potassium channels (K(ATP) channels) regulate vascular tone and cardiac contraction through their action on the membrane potential of smooth muscle cells and cardiomyocytes. Because aging and diseases alter K(ATP) channel activity, many pharmacological treatments aimed at improving their function, therefore cardiovascular function, have been evaluated. Nicorandil, a K(ATP) channel opener, nitric oxide donor and antioxidant, is used as a treatment of angina pectoris and induces vasodilation, blood pressure decrease and cardioprotection in aging as well as after ischemia-reperfusion. Here, using the patch-clamp technique, we have studied the effect a chronic low dose of nicorandil (0.1 mg/kg per day for 2 months), on the activity of cardiomyocyte K(ATP) channels as a function of age, in newborn, 4-, 12- and 24-month old rats. Nicorandil exerted an anti-oxidant and protective action on cardiomyocyte K(ATP) channels, especially in aged animals, leading to restoration of a normal channel activity. These findings could justify further therapeutical applications.
Raveaud
Stéphanie
S
Université Joseph Fourier, Grenoble, France.
Verdetti
Jean
J
Faury
Gilles
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D004136:Dinitrobenzenes / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D054086:KATP Channels / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D020108:Nicorandil / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
D000889:Anti-Arrhythmia Agents; D004136:Dinitrobenzenes; D007004:Hypoglycemic Agents; D054086:KATP Channels; D020108:Nicorandil; D000255:Adenosine Triphosphate; C010936:2,4-dinitrothiocyanatobenzene; D005905:Glyburide