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To study the effect of selective alpha 1- or alpha 2-adrenergic blockade on the myocardial contractile and chronotropic response to exercise, 29 dogs were chronically instrumented with a sonomicrometer for measuring myocardial wall thickness and a micromanometer for measuring left ventricular pressure. During treadmill exercise, either the selective alpha 1-blocker prazosin (80 micrograms/kg, n = 12) or the alpha 2-blocker idazoxan (80 micrograms/kg, n = 8) was infused into the left atrium beginning 2-3 minutes after the onset of exercise. alpha 1-Adrenoceptor blockade, like alpha 2-adrenoceptor blockade, was found to cause significant increases in systolic wall thickening, thickening velocity, heart rate, and left ventricular contractility, indicating an increase in inotropic state that was comparable to that with alpha 2-adrenoceptor blockade. Preventing the decrease in aortic blood pressure after selective alpha 1-blockade by using either systemic angiotensin II infusion (n = 6) or inflation of an intra-aortic balloon (n = 6) did not prevent the observed increases in wall thickening, heart rate, and left ventricular contractility. In four of the dogs treated with prazosin, the norepinephrine concentration in the coronary sinus was found to more than double after alpha 1-blockade. beta-Adrenergic blockade (propranolol, 1.0 mg/kg) prevented the increased contractile and chronotropic state caused by alpha 1- or alpha 2-blockade. Selective alpha-adrenergic blockade during adrenergic activation by intravenous norepinephrine infusion, in contrast to exercise, had no effect on wall thickening, heart rate, or left ventricular contractility. These data indicate that selective alpha 1-adrenergic blockade, like selective alpha 2-adrenergic blockade, causes a significant augmentation of heart rate and left ventricular contractility in the dog during dynamic exercise. These data are consistent with the hypothesis that this occurs through a presynaptic disinhibition of neural norepinephrine release mediated by a prejunctional alpha 1-adrenoceptor.

Myocardial effects of selective alpha-adrenoceptor blockade during exercise in dogs.