β-Adrenergic receptor number and adenylate cyclase function in denervated transplanted and cardiomyopathic human hearts

To test the hypothesis that there is up-regulation of beta-adrenergic receptor density or supersensitivity of beta-adrenergic receptor-stimulated adenylate cyclase in the denervated transplanted human heart, we studied myocardium from transplanted, normal, and failing hearts. Myocardium was obtained from 10 patients 9 +/- 3 months after cardiac transplantation, from 10 patients without cardiac disease, and from eight patients with symptomatic congestive heart failure due to idiopathic cardiomyopathy. beta-Adrenergic receptor density in transplanted myocardium (15 +/- 3 fmol/mg protein, 1.20 +/- 0.14 fmol/mg DNA) was not different from that in normal myocardium (22 +/- 3 fmol/mg protein, 1.46 +/- 0.13 fmol/mg DNA; p = NS for both). In myocardium from cardiomyopathic hearts, beta-adrenergic receptor density was markedly reduced (8 +/- 2 fmol/mg protein, 0.84 +/- 0.13 fmol/mg DNA; p less than 0.05 and p less than 0.01 vs. normal myocardium, respectively). Likewise, the response of adenylate cyclase to isoproterenol in transplanted myocardium was not significantly different from that in normal myocardium, but the response was markedly depressed in cardiomyopathic myocardium. Although forskolin-stimulated adenylate cyclase activity was similar in all three groups, guanine nucleotide-stimulated adenylate cyclase activity was markedly reduced in transplanted myocardium (20 +/- 17 vs. 78 +/- 13 pmol/mg/min for normal myocardium, p less than 0.01) and to a lesser degree in cardiomyopathic myocardium (39 +/- 14 pmol/mg/min, p less than 0.03 vs. normal myocardium). Thus, there is no evidence of beta-adrenergic receptor up-regulation or supersensitivity in denervated transplanted human myocardium.