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We examined, in conscious dogs, the potential role of prejunctional alpha 2-adrenergic receptors for the regulation of heart rate and contractility response to exercise through modulation of the neurotransmitter release. Changes in heart rate and left ventricular pressure with time during comparable exercise levels, together with changes in norepinephrine concentration in the coronary sinus, were compared before and after the intravenous administration of: prazosin (0.5 mg/kg), a preferential postjunctional alpha 1-adrenergic receptor blocking agent; phentolamine (1 mg/kg), a nonselective alpha-adrenergic blocking agent; and yohimbine (0.3 mg/kg), a preferential prejunctional alpha 2-adrenergic receptor blocking agent. During exercise after phentolamine or yohimbine, changes in heart rate and left ventricular dP/dt were markedly potentiated compared to the control exercise, as well as to exercise after prazosin, whereas the norepinephrine concentration in the coronary sinus was substantially elevated. After intracoronary administration of phentolamine (0.1 mg/kg) or yohimbine (0.03 mg/kg), heart rate and contractility response to exercise were also potentiated, compared to the control exercise. These observations indicate that, in the intact conscious animal, prejunctional alpha 2-adrenoreceptors are stimulated during exercise, thereby modulating the norepinephrine release through a negative feedback inhibitory mechanism. Blocking these receptors by phentolamine or yohimbine results in an uncontrolled norepinephrine release during exercise associated with an augmented beta-adrenergic receptor-mediated end organ response, i.e., a potentiation in heart rate and contractility response.

Role of prejunctional alpha 2-adrenergic receptors in the regulation of myocardial performance during exercise in conscious dogs.