Key result
Systemic 6-hydroxydopamine and α-methyl-p-tyrosine reduce ouabain-induced contractility by up to ~83% in dogs.
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Indicates catecholamine dependence of ouabain inotropy in dogs; leaves open relevance to human cardiac glycoside therapy.
The action of ouabain on myocardial inotropism pretreated with 6-hydroxydopamine and α-methyl-p-tyrosine was studied. Inotropic action of ouabain was not changed by depletion of catecholamines in the brain, in which the central sympathetic neurons were destroyed by an intraventricular administration of 6-hydroxydopamine. Systemic administration of 6-hydroxydopamine and α-methyl-p-tyrosine reduced ventricular catecholamines to 5.3% and 20.8% of the control, respectively. Percent increase of contractility by ouabain after the pretreatment of 6-hydroxydopamine and α-methyl-p-tyrosine was reduced to 16.7% and 50.2% of the control, respectively. The results obtained suggest that catecholamines in the myocardium play some important role in producing cardiotonic action of cardiac glycosides. Brain catecholamines or the central sympathetic nervous system do not appear to participate in the exertion of the positive inotropic action of cardiac glycosides.
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Shudo et al. (1975) studied this question. Ouabain after pretreatment with 6-hydroxydopamine and α-methyl-p-tyrosine vs. Ouabain without pretreatment (control) was evaluated on Percent increase of contractility by ouabain. Systemic pretreatment with 6-hydroxydopamine and α-methyl-p-tyrosine reduced the positive inotropic action of ouabain to 16.7% and 50.2% of control, respectively, in dogs.
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