This proposal is a multidisciplinary study of the cellular and biochemical basis for alterations in the mechanical performance of the heart during induction and regression of cardiac hypertrophy. Various animal models of hypertrophy will be studied, including hypertrophy induced by hormones (thyroxine and isoproterenol) and pressure and volume overload. We shall focus our investigations particularly on three general areas: 1) the role of adaptative changes in the contractile proteins in the altered mechanical performance of hypertrophied hearts, 2) the nature of the biochemical events that initiate cardiac hypertrophy and 3) the role of the autonomic nervous system and other neurohumoral factors in the modulation of compensatory myocardial growth. The latter area will include studies on the role of taurine in various forms of hypertrophy. Investigators within the institution will combine their resources, using common animal models to explore fundamental mechanisms involved in cardiac hypertrophy. This proposal represents an extension of collaborative efforts that already are underway in various laboratories. Mechanisms have been established for communication of data, critical review of research in progress and administrative control of all aspects of this project.
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