Re-expression of the cardiac fetal gene program in L-NAME hypertension.

Abstract

This myocardial response to work overload is associated with a complex reprogramming of the expression of cardiac "fetal genes" such as beta-myosin heavy chain (MHC), atrial natriuretic factor (ANF), and brain natriuretic peptide (BNP). The up-regulation of ANF and BNP is viewed as an event related to the antigrowth properties of those peptides. Little is known about factors that underlie this up-regulation in vivo. In the present work, the contribution of chronic hemodynamic overload on ANF and BNP gene expression was determined in No-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, induced hypertension which may develop with or without hypertrophy. The hypothesis states that chronic hemodynamic overload without attendant hypertrophy would not upregulate ANF and BNP gene expression. The studies were carried out in the context provided by other markers of cardiac hypertrophy including beta-MHC, collagen III as well as the parameters associated with cardiac hypertrophy such as LV renin expression, plasma renin activity (PRA) and angiotensin converting enzyme (ACE) activity, given the coincidental activation of this renin-angiotensin system (RAS) and the development of hypertrophy. (Abstract shortened by UMI.)