Induction of cardiac beta-adrenergic receptor kinase 1 in rat heart failure caused by coronary ligation

beta-adrenergic receptor kinase 1 (beta ARK(1)) participates in the desensi tization of beta-adrenergic receptors by uncoupling the signal transduction . The present study was designed to examine whether neurohumoral increase i s crucial for the activation of beta ARK(1) in heart failure. Four weeks af ter the ligation of rat coronary artery, LV dP/dt max was reduced, cardiac response to isoproterenol was impaired, and ratio of right ventricular weig ht to body weight, an index of cardiac hypertrophy, was increased. At the s ame time, beta ARK(1) expression and activity were augmented in the hypertr ophied hearts. In addition, plasma norepinephrine content was enhanced in a ccordance with cardiac hypertrophy, cardiac beta ARK(1) expression, LV dP/d t max, and LVEDP. These results of the present study suggest that beta ARK( 1) is augmented in concert with circulating norepinephrine level and that b eta ARK(1) may account for, at least in part, the cardiac dysfunction in ra t with myocardial infarction, (C) 1999 Academic Press.