Age-associated alternations in cardiac P -adrenergic receptor signaling

During aging, cardiac contractile response to P-AR stimulation is decreased in humans and animal models. Recent studies demonstrate that the positive inotropic effects of both f^-AR and P2-AR stimulation are significantly decreased with aging. This is accompanied by decreases in both P-AR subtype densities and a reduction in membrane adenylyl cyclase activity. However, neither G protein-coupled receptor kinases (GRKs) nor inhibitory G proteins (G.) appears to contribute to the age-associated reduction in the P-AR modulation of contraction. Thus, while both aging and chronic heart failure exhibit a diminution in cardiac P-AR responsiveness, only heart failure exhibits increased GRK-mediated dcsensitization of p-ARs and an upregulation of G proteins.