α-Adrenergic Regulation of Myocardial Performance in the Exercising Dog: Evidence for Both Presynaptic α₁- and α₂-Adrenoceptors

Summary

New evidence supporting both presynaptic α₁- and α₂-adrenoceptors playing a role in the regulation of myocardial contractile performance in the exercising dog is reviewed. Studies utilized chronically instrumented dogs having sonomicrometers for the measurement of regional wall thickening and transducers for the measurement of left ventricular and systemic hemodynamics. During steady state exercise, either the selective α₁-adrenoceptor blocker prazosin (80μg/kg) or the selective α₂-adrenoceptor blocker idazoxan (80μg/kg) was infused into the left atrium while exercise continued. Immediately following the administration of either α-adrenoceptor blocking agent, there were substantial increases in heart rate, left ventricular dP/dt and regional contractile function as assessed using sonomicrometers, and norepinephrine release by the myocardium increased substantially. β-adrenergic blockade prevented the heart rate and contractile effects of either α₁ - or α₂-adrenoceptor blocker whereas norepinephrine release was further enhanced. These effects could not be attributed to baroreceptor unloading. In dogs studied under resting conditions with norepinephrine infusion to produce an increase in dP/dt similar to that observed during treadmill exercise, no sympathetic augmentation was observed following either α-blocker. Together, these studies provide evidence that both α₁- and α₂-adrenoceptors participate in the modulation of sympathetic neuronal norepinephrine release in the canine myocardium.