Function of myocardial alpha-adrenoceptors

In addition to beta-adrenoceptors (beta ARs), cardiac myocytes of animals and man possess alpha 1ARs, but not alpha 2ARs. Norepinephrine and epinephrine have a higher affinity for myocardial alpha 1ARs than for beta ARs. Unlike beta AR stimulation, myocardial alpha 1AR stimulation does not increase the slow inward current. The alpha 1AR-mediated positive inotropic effect seen in isolated heart preparations appears to involve increased Ca sensitivity of myofibrils and production of inositol triphosphate (IP3) and diacylglycerol (DAG), but the functions of IP3 and DAG are not clear. Myocardial alpha 1AR stimulation reduces rate of isolated atria and Purkinje fibers and lengthens refractory period and action potential duration. Hypoxia increases alpha 1AR density in cardiomyocytes. alpha 1AR-mediated arrhythmias occur in isolated Purkinje fibers during hypoxia, following infarction, and in the presence of Ba2+ or high Ca2+. In animals, coronary artery occlusion and/or reperfusion increase myocardial alpha 1AR density and responsiveness, and alpha AR blocking drugs attenuate arrhythmias. However, an antiarrhythmic effect of alpha AR blocking drugs mediated by action on coronary vascular alpha ARs cannot be excluded. Presently available drugs do not differentiate between myocardial and vascular alpha ARs and thus affect the coronary and systemic circulations and, indirectly, the heart. Additional myocardial alpha 1AR-mediated effects include production of cardiac hypertrophy, stimulation of glucose uptake and phosphofructokinase and cyclic AMP phosphodiesterase activity, and release of atrial natriuretic peptide.