Function of myocardial α-adrenoceptors

In addition to ß-adrenoceptors (ßARs), cardiac myocytes of animals and man possess α 1ARs, but not α 2ARs. Norepinephrine an epinephrine have a higher affinity for myocardial α 1ARs than for ßARs. Unlike ßAR stimulation, myocardial α 1AR stimulation does not increase the slow inward current. The α 1AR-mediated positive inotropic effect seen in isolated heart preparations appears to involve increased Ca sensitivity of myofibrils and production of inositol triphosphate (IP 3) and diacylglycerol (DAG), but the functions of IP 3 and DAG are not clear. Myocardial α 1AR stimulation reduces rate of isolated atria and Purkinje fibers and lengthens refractory period and action potential duration. Hypoxia increases α 1AR density in cardiomyocytes. α 1AR-mediated arrhythmias occur in isolated Purkinje fibers during hypoxia, following infarction, and in the presence of Ba 2+ or high Ca 2+. In animals, coronary artery occlusion and /or reperfusion increase myocardial α 1AR density and responsiveness, and αAR blocking drugs attenuate arrhythmias. However, an antiarrhythmic effect of αAR blocking drugs mediated by action on coronary vascular αARs cannot be excluded. Presently available drugs do not differentiate between myocardial and vascular αARs and thus affect the coronary and systemic circulations and, indirectly, the heart. Additional myocardial α 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.