Upregulation of β-adrenergic receptors in heart failure due to volume overload

To examine the mechanisms of changes in β-adrenergic signal transduction in heart failing due to volume overload, we studied the status of β-adrenoceptors (β-ARs), G protein-coupled receptor kinase (GRK), and β-arrestin in heart failure due to aortocaval shunt (AVS). Heart failure in rats was induced by creating AVS for 16 wk, and β-AR binding, GRK activity, as well as their protein content, and mRNA levels were determined in both left and right ventricles. The density and protein content for β1-ARs, unlike those for β2-ARs, were increased in the failing hearts. Furthermore, protein contents for GRK isoforms and β-arrestin-1 were decreased in membranous fractions and increased in cytosolic fractions from the failing hearts. On the other hand, steady-state mRNA levels for β1-ARs and GRK2, as well as protein content for Gβγ-subunits, did not change in the failing heart. Basal cardiac function was depressed; however, both in vivo and ex vivo positive inotropic responses of the failing hearts to isoproterenol...