Modulation of positive inotropy and metabolic coronary dilatation by myocardial α-adrenoceptors

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Abstract
Cardiac hyperactivity and its consequent metabolically induced coronary vasodilatation (MCD) were studied in isolated, perfused, electrically paced rat hearts. The α-adrenoceptor agonists, phenylephrine and methoxamine, produced a concentration-dependent inhibition of the inotropic responses to noradrenaline, dobutamine, isoprenaline, tyramine, and glucagon, while relatively potentiating their MCD reactions. This inhibition was unrelated to the α-agonists' known inotropic action and was not affected by catecholamine depletion of the heart. Withdrawal of the α-agonists or administration of the α-adrenoceptor antagonists phentolamine, phenoxybenzamine, or prazosin returned the inotropic and MCD reactions to normal. Neither the MCD response to electrically induced tachycardia nor the inotropic reactions produced by calcium chloride were affected by α-adrenoceptor agonists or antagonists. Alone, α-adrenoceptor antagonists were shown to potentiate the inotropic responses to noradrenaline and isoprenaline while the MCD was relatively diminished. The responses to glucagon were unaltered by α-antagonists. We postulate that myocardial reactivity to sympathetic stimulation can be modulated through α-adrenoceptors by the inhibition of processes that mediate cardiostimulation at post-β-adrenoceptor sites, together with facilitation of those leading up to MCD. Accordingly, this modulation would act to prevent ischaemic damage to the heart by acting to limit the inotropic responses to increasing sympathetic stimulation while maximizing the blood supply to the myocardium.