Differentiation of Cardiac and Peripheral Alpha- and Beta-Adrenergic Responses to Dobutamine, Etilefrine and Xylometazoline in Dogs

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Abstract
To evaluate whether peripheral and/or cardiac .alpha.-adrenoceptors were involved in the cardiac effects of sympathomimetric drugs, the effects of phenoxybenzamine (1 mg/kg body wt) on increasing, graded doses of dobutamine, etilefrine and xylometazoline were investigated in anesthetized dogs. Measurements were made of simultaneous changes in left ventricular pressure, rate of rise of left ventricular pressure (dP/dt), aortic blood pressure, peripheral blood flow and heart rate. To determine the actual contractile responses independent of hemodynamic influences on the myocardium, all drugs were studied under conditions of fixed mean aortic pressure and heart rate. Dobutamine produced increases in dP/dtmax which remained unaffected by phenoxybenzamine; the blood pressure increase was antagonized. The contractile responses were less pronounced under fixed blood pressure conditions, demonstrating that part of the inotropic response to dobutamine is attributable to an .alpha.-receptor-mediated increase of the afterload. The primary effect on myocardium is assumed to be mediated by .beta.1-receptors. In contrast to conditions of uncontrolled hemodynamics, etilefrine produced only small increases in contractility. Since these effects were antagonized by phenoxybenzamine and phentolamine (0.5 mg/kg body wt), it can be postulated that the canine heart contains a population of adrenergic .alpha.-receptors. A further subtype of .alpha.-receptor must exist, since xylometazoline produced negative inotropic responses which were prevented by phenoxybenzamine and were even potentiated when .alpha.-receptor-mediated increase of the afterload was eliminated by fixing the blood pressure. Apart from .alpha.-receptors situated in the myocardium, the sinus node must also contain both receptor subtypes since the positive chronotropic response to etilefrine and the negative chronotropic response to xylometazoline were inhibited by phenoxybenzamine.