In idiopathic dilated cardiomyopathy, functional improvement related to treatment with beta-blockers is associated with changes in myocardial gene expression.

The third-generation beta-blocking agent carvedilol has substantially different effects on left ventricular function, hemodynamics, adrenergic activity, and beta-receptor expression than dose the second-generation compound metoprolol. Some or all of these differences may explain the apparent differences in clinical results between the two compounds.

These data indicate that: (a) Adrenergic neuroeffector abnormalities present in the failing human heart are due to local mechanisms; systemic processes do not produce j-adrenergic neuroeffector abnormalities. (b) Pressure-overloaded failing right ventricles of PPH subjects exhibit decreased activity of the catalytic subunit of adenylate cyclase, an abnormality not previously described in the failing human heart. (J.

Background Aging decreases cardiac 83-adrenergic responsiveness in model systems and in humans in vivo. The purpose of this study was to comprehensively evaluate the age-related changes in the /3-receptor-G protein-adenylyl cyclase complex in nonfailing human hearts.Methods and Results Twenty-six nonfailing explanted human hearts aged 1 to 71 years were obtained from organ donors and subjected to pharmacological investigation of