Possible mechanisms for inotropic actions of vanadate in isolated guinea pig and rat heart preparations.
The mechanism of inotropic actions of vanadate studied in isolated, electrically stimulated atrial and ventricular muscle preparations of rat or guinea-pig heart. Vanadate produced a negative inotropic effect in guinea-pig left atrial preparations associated with a marked shortening of the action potential plateau. In guinea-pig papillary muscle, or rat atrial or ventricular muscle preparations, vanadate produced a positive inotropic effect, which was not affected by either propranolol, phentolamine or metiamide. The positive inotropic effect was observed when action potential duration was either increased or decreased. Inotropic concentrations of vanadate failed to significantly alter the ouabain-sensitive 86Rb+-uptake, an estimate of sodium pump activity, or tissue concentration of cyclic AMP in electrically stimulated preparations. In partially depolarized rat atrial preparations in which fast sodium channels were inactivated in the presence of a high concentration of K+ (22 mmol/l), vanadate restored electrical activity (calcium-dependent action potentials) and the contraction, similar to isoproterenol. This action of vanadate was abolished by Mn2+, a slow channel inhibitor, but not by tetrodotoxin. The characteristic of vanadate- and isoproterenol-restored preparations, however, were substantially different. Moreover, vanadate failed to restore the contraction or action potential in partially depolarized guinea pig atrial preparations unlike isoproterenol. These results indicate that vanadate may either enhance or inhibit slow channels in cardiac muscle.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003864:Depression, Chemical; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical; D014638:Vanadates; D014639:Vanadium / Q000494:pharmacology*
D007473:Ion Channels; D014639:Vanadium; D014638:Vanadates; D012964:Sodium; D000242:Cyclic AMP