[Alpha-adrenergic control of coronary circulation and left ventricular function during exertion]

Abstract

Sympathetic activation is responsible for a striking inotropic and chronotropic response as well as for important coronary hyperemia during exercise. However the exact role of the coronary and myocardial alpha adrenergic receptors during sympathetic activation is not well defined. It is well accepted that coronary artery smooth muscle contains both alpha-1 and alpha-2 adrenergic receptors which elicit a vasoconstrictor response upon neurogenic and humoral stimulation. It seems however paradoxical that coronary vasoconstriction should occur in conditions of increased myocardial oxygen consumption such as during exercise. On the other hand, presynaptic alpha-2 receptors have been identified at the sympathetic nerve endings which, when stimulated by the locally released norepinephrine, will attenuate further norepinephrine release through a negative feed-back mechanism. A possible regulatory role of this mechanism for the left ventricular and coronary flow response during exercise has not been established. The major goal of this work was to define the exact role of alpha adrenergic receptors for the regulation of cardiac function and coronary circulation during exercise. Left ventricular function, coronary circulation, myocardial metabolism and catecholamine release were analysed during standardized treadmill exercise in conscious chronically instrumented dogs, prior to and following the administration of different alpha receptor blockers with different affinities for the different subtypes of alpha receptors. Three series of experiments were conducted to clarify: 1. the role of postsynaptic alpha receptors for the regulation of coronary blood flow during exercise, 2. the role of presynaptic alpha receptors for the regulation of left ventricular function during exercise, and 3. the role of postsynaptic alpha receptors for the regulation of transmural myocardial blood flow distribution during exercise. Dogs were instrumented with a solid state pressure transducer in the left ventricular cavity, a Doppler flow probe around the left circumflex coronary artery, and silastic catheters in aorta, left atrium and coronary sinus. 2-3 weeks after surgery the dogs were subjected to standard treadmill exercise. Simultaneous and continuous measurements were performed of heart rate, left ventricular systolic and end diastolic pressure, LV dP/dt/P, mean arterial pressure, late diastolic coronary vascular resistance, regional myocardial blood flow, myocardial oxygen consumption and plasma catecholamines. In the first series of experiments, coronary blood flow and myocardial oxygen consumption were analyzed in 15 conscious dogs at rest and during exercise prior to and following IV administration of phentolamine (1 mg/kg) or prazosin (0.5 mg/kg).(ABSTRACT TRUNCATED AT 400 WORDS)