Expression of c-fos mRNA by Acute Pressure Overload in Perfused Rat Heart

Abstract

It has been demonstrated that several mechanical or pharmacological overload to the heart induces immediate early gene expression such as protooncogenes and heat shock protein genes and acceler¬ates the cardiac protein synthesis to lead to cardiac hypertrophy. Norepinephrine induces cardiac hypertrophy and specific gene expression in cultured rat cardiac myocytes via α1-adrenergic recep¬tor [1,2]. Mechanical stimuli (myocyte stretching) directly induce c-fos expression in cultured neonatal rat cardiac myocytes and this response was associated with protein kinase C activation[3,4]. In these experimental models the induction of specific protooncogene expression in response to several cardiac overload might be mediated by α1-adrenergic receptor or protein kinase C-dependent signal transduction system. On the other hand, Morgan et al[5] have reported that increases in tissue cAMP content by acute pressure overload results in acceleration of protein synthesis rates in perfused adult rat hearts and that the effects of ventricular wall stretch by acute elevation of aortic pressure to accelerate synthesis may involve a cAMP-dependent protein synthesis mechanism. Our hypothesis was that protooncogene c-fos expression enhanced by acute pressure overload in adult rat hearts would play a transducing role in the cAMP-dependent protein synthesis mechanism in addition to protein kinase C-dependent mechanism. In the present study cAMP content, c-fos mRNA expres¬sion, and rates of protein synthesis were examined in adult rat hearts that were perfused at elevated aortic pressure or exposed to hormone receptor binding (glucagon) in order to determine whether c-fos expression by acute pressure overload coupled with an increase in cAMP content and continuous¬ly accelerated rates of protein synthesis.