Blockade During Exercise in Dogs

To study the effect of selective cvlor a2-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 a1-blocker prazosin (80 ,ug/kg, n= 12) or the a2-blocker idazoxan (80 ,g/kg, n=8) was infused into the left atrium beginning 2-3 minutes after the onset of exercise. al-Adrenoceptor blockade, like a!2adrenoceptor 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 a2-adrenoceptor blockade. Preventing the decrease in aortic blood pressure after selective ca,-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 a1-blockade. f-Adrenergic blockade (propranolol, 1.0 mg/kg) prevented the increased contractile and chronotropic state caused by a1or ca2-blockade. Selective a-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 ael-adrenergic blockade, like selective a£2adrenergic 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 a1-adrenoceptor. (Circulation Research 1990;66:1703-1712)