Cardiac hypertrophy (CH) is a major risk factor for cardiovascular mortality and morbidity. The hypertrophied heart is qualitatively different from its normal counterpart, and expresses different amounts of major muscle proteins, such as myosin heavy-(MHC) and light-(MLC) chains. In our studies of cardiac hypertrophy (CH), we sought to: 1. examine the relationship between biochemical changes in muscle proteins and the development of CH, in different models of CH in rats, and 2. examine the functional significance of biochemical changes in CH. For this purpose, CH was induced by different means, and morphological and biochemical/molecular characteristics of CH were examined. We found that different patterns of CH were induced by different stimuli. These patterns are best exemplified by the comparison of CH induced by isoproterenol (ISO) and by phenylephrine (PE): ISO induces CH in all rats. The extent of ISO-CH decreases with age, and is equal in males and females. In contrast, PE induces CH only in some animals, without any correlation to changes in blood pressure. The percentage of animals that develop CH in response to PE increases with age, and is greater in males than in females. ISO-induced CH develops rapidly (within days), and regresses quickly after cessation of the stimulus. PE-induced CH is slow to develop and to regress. Biochemically, PE-CH is characterized by an increased ratio of beta-myosin heavy chain (b-MHC) to alpha-MHC, whereas ISO-CH presents with a decrease in this ratio. The change in MHC-isoforms by PE occurs equally in animals that respond to PE with CH, and in those that do not, indicating that the MHC change and CH are independent adaptive processes. The motility of labeled actin filaments on myosin extracted from hearts of PE-treated rats was normal, as determined by the """"""""in vitro motility assay"""""""" (performed by Dr. G. Cuda, Lab. of Mol. Cardiol., NHLBI). In contrast, actin motility on myosin extracted from hearts of ISO treated rats exhibited increased cycling rate. Thus, alpha- and beta-adrenergic stimuli induce distinct patterns of CH, which differ in: the rate of induction and reversal of CH, susceptibility to develop CH varies according to age and gender, the percentage that develop CH, and biochemical and functional changes that accompany CH.
