Signal Transduction in Myocardial Hypertrophy

Abstract

Transduction of stretch of the ventricular wall into accelerated growth and ultimately hypertrophy of cardiac muscle cells is a cyclic AMP (cAMP) dependent phenomenon. When stretch was induced in isolated perfused rat hearts by an increase in aortic pressure from 60 to 120 mmHg, protein synthesis was accelerated during the second hour of perfusion. Only a brief exposure to higher aortic pressure (2 min) was required to elicit this effect. Elevation of aortic pressure also increased cAMP content. Other interventions that increased cAMP content such as glucagon increased second hour rates of protein synthesis. Stretch of the ventricular wall had a more rapid effect on ribosome formation. During the first hour of perfusion, increased aortic pressure raised rates of 60S ribosomal subunit formation by 38% in the absence of added insulin and 35% in the presence of the hormone. Ribosome formation was also accelerated by addition of glucagon. The muscarinic cholinergic agonist, methacholine blocked the effects of elevated aortic pressure on protein synthesis, ribosome formation, and cAMP content. These studies indicate that stretch of the ventricular wall is transduced into greater cAMP content and that this intracellular messenger is one of the substances responsible for accelerated ribosome formation and protein synthesis.