Cardiac alphai-adrenergic receptor stimulation: Positive inotropism and arrhythmias (part 10). CHRONOTROPIC AND ARRHYTHMOGENIC EFFECTS

Automatic arrhythmias, as well as induced delayed afterdepolarization and triggered activity produced by alpha1-adrenergic receptor stimulation, are suggested to be related to activation of the Na-H antiport. Indeed such an activation, as well as the activation of the Na-HCO3 symport, should increase intracellular sodium and lead to calcium overload by a net uptake of calcium via the Na/Ca exchanger; this occurs whether the exchanger is in its reverse mode or in its direct mode because, in the latter case, reduced calcium extrusion by the Na/Ca exchanger does not compensate basal calcium leak. However, alpha1-adrenergic stimulation also stimulates Na+/K+-ATPase , so that, unless this pump is inhibited, adrenergic receptor agonists have not been shown to increase intracellular sodium. In support of this view are two sets of experimental results. First, stimulation of the alpha1-adrener-gic receptors potentiates the development of digitalis glycoside cardiotoxicity .Alpha1-adrenergic stimulation may aggravate digitalis-induced contractures by enhancing Na-H antiport activity, leading to increases in intracellular sodium (and thus calcium) and pH. Second, anomalous electrical activity in simulated ischemic conditions as well as in digitalis cardiotoxicity is antagonized by Na-H antiport blockers . Recent evidence emphasizes the role of alpha1A-adrenoreceptor subtypes in ischemic arrhythmias because they are significantly reduced by WB-4101 . Moreover, this increase in abnormal automaticity, which is transduced by a pertussis toxin-sensitive G-protein, should be distinguished from the mechanism underlying the increase in automaticity in normal Purkinje fibres, which is independent of the pertussis toxin substrate. It’s your turn to benefit from the shopping whenever you need efficient levitra sale that will be sure to work for your problem. This is now all very much possible at the best online pharmacy you have ever come across offering it services to you and other international customers interested.