Lithium chloride-induced cardiovascular changes in rabbits are mediated by adenosine triphosphate-sensitive potassium channels.
The effect of lithium chloride on the mean arterial blood pressure, heart rate and heart contractility was evaluated in rabbits. The intravenous administration of 50 mg kg-1 lithium chloride as a bolus injection into rabbits produced a progressive decrease in the mean arterial blood pressure, heart rate and heart contractility during the 2-h period of investigation. Pretreatment of animals with 5 mg kg-1 glibenclamide, a potent inhibitor of adenosine triphosphate-sensitive potassium channels, markedly inhibited the cardiovascular changes induced by lithium chloride. Doubling the dose of glibenclamide nearly abolished these effects of lithium chloride. Similarly, lithium chloride produced a concentration- dependent relaxation of noradrenaline-induced contractions in isolated aortic strips of rabbits. This relaxant effect of lithium chloride was inhibited by pretreatment of the aortic strips with glibenclamide. Doubling the concentration of glibenclamide in the bathing fluid nearly abolished the effect of lithium. Diazoxide and verapamil potentiated the relaxant effect of lithium chloride on the isolated noradrenaline-contracted aortic strips. Pretreatment with glibenclamide markedly reversed the effect of diazoxide but not that of verapamil. The intravenous administration of lithium was also found to be capable of increasing the plasma potassium level and of decreasing the intracellular levels of adenosine triphosphate in cardiac and vascular tissues in a time-dependent manner. The plasma sodium and calcium levels were not changed. These results provide evidence that the hypotensive and cardiac depressant effects of lithium chloride are mediated by activation of adenosine triphosphate-sensitive potassium channels.
Abdel-Zaher
A O
AO
Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Abdel-Rahman
M M
MM
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D018692:Antimanic Agents / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007275:Injections, Intravenous; D018021:Lithium Chloride / Q000633:toxicity*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011817:Rabbits
D018692:Antimanic Agents; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D018021:Lithium Chloride; D005905:Glyburide