Norepinephrine increases beta-receptors and adenylate cyclase in canine myocardium

Norepinephrine, a known inducer of myocardial hypertrophy, was found to have marked effects on the myocardial adrenergic system, which occurred prior to the development of a significant increase in heart weight. The chronic subhypertensive infusion (1.4 microgram/min) in free-roaming dogs produced a threefold increase in plasma norepinephrine (determined by radioimmunoassay). After 3 mo of infusion, right and left ventricular norepinephrine content (ng/mg protein) decreased significantly by twofold (right, 2.50 +/- 0.24; left, 2.08 +/- 0.36) compared with controls (right, 4.76 +/- 1.48; left, 4.65 +/- 1.49), and beta-receptor density (125I-pindolol) increased (right, 0.122 +/- 0.029; left, 0.153 +/- 0.021) over the controls (right, 0.082 +/- 0.015; left, 0.069 +/- 0.008 pmol/mg protein). Accompanying the beta-receptor changes, isoproterenol-stimulated adenylate cyclase activity also increased significantly [right, 29.2 +/- 2.1; left, 29.5 +/- 1.0 vs. controls, right, 13.8 +/- 1.1; left, 20.2 +/- 2.2 pmol adenosine 3',5'-cyclic monophosphate (cAMP) generated X min-1 X mg protein-1]. Because the above changes occurred in the absence of cardiac hypertrophy, it suggests that alterations in the myocardial adrenergic system are dependent on the stimulus (in this case norepinephrine) invoking the change and not the degree of hypertrophy. It also suggests that changes in the adrenergic system may not directly reflect the mechanism involved in the development of hypertrophy.