FUNCTION OF MYOCARDIAL ALPHA-ADRENOCEPTORS

In addition to ß-adrenoceptors (ßARs), cardiac myocytes of animals and man possess α1ARs, but not α2ARs. Norepinephrine an epinephrine have a higher affinity for myocardial α1ARs than for ßARs. Unlike ßAR stimulation, myocardial α1AR stimulation does not increase the slow inward current. The α1AR-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 α1AR stimulation reduces rate of isolated atria and Purkinje fibers and lengthens refractory period and action potential duration. Hypoxia increases α1AR density in cardiomyocytes. α1AR-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 α1AR 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 α1AR-mediated effects include production of cardiac hypertrophy, stimulation of glucose uptake and phosphofructokinase and cyclic AMP phosphodiesterase activity, and release of atrial natriuretic peptide. © 1990.