Positive Inotropic Effect without Cyclic AMP Elevation after α–Adrenergic Stimulation of Perfused Hearts from Hypothyroid Rats

AbstractPrevious experiments suggested that the positive inotropic response to α–adrenergic stimulation was unrelated to cyclic AMP in contrast to the inotropic effect of β–adrenergic stimulation. In order to elucidate this question further we perfused hearts from rats made hypothyroid by treatment with propyl–thiouracil, since this treatment is known to augment the myocardial α–adrenergic effects. α–stimulation (phenylephrine in the presence of propranolol) caused a marked inotropic response and no increase in cyclic AMP. In contrast β–stimulation (isoprenaline) increased the cyclicAMPcontent. The time–courses of the inotropic responses to α– and β–stimulation were different. The aortic pressure waves indicated a shorter duration of each contraction phase after isoprenaline than after phenylephrine in the presence of propranolol. This difference is probably due to the cyclic AMP accumulated after isoprenaline. The findings support the hypothesis that the positive inotropic effect of α–adrenergic stimulation is caused by mechanisms independent of cyclic AMP, while the β–adrenergic inotropic effect involves cyclic AMP mediated processes. Such a dual mechanism of action for adrenergic agents might serve to maintain responsiveness of the heart under various conditions.