Research from our laboratory has established that the cause of development or reversal of myocardial hypertrophpy (MH) cannot be explained by alteration of blood pressure (BP) level alone. Antihypertensive drug therapy suggested that, in addition to BP control, the adrenergic system may play an important role in reversing MH. We have shown that the MH is a result of increase in both collagens and non-collagenous protein. A detailed study on collagen protein showed an increase in concentration, content, and rate of synthesis of collagen in 6 months old SHR associated with a significant alteration in collagen phenotypes, all of which can be prevented by antihypertensive therapy. While the in vivo study suggested the involvement of Beta-adrenergic system in the reversal of hypertrophy, our preliminary data using isolated myocytes in vitro (independent of BP and hemodynamic change) demonstrated the existence of a humoral factor(s) in the SHR ventricle which stimulated protein synthesis. All these observations led us to continue the investigation with the following aims: 1) to investigate the possible fundamental changes in both contractile element of the heart (myosin, its ixozyme and Ca++ ATPase) and collagen phenotypic pattern of MH in response to stress, such as longstand-hypertension, and after its reversal or prevention by antihypertensive drug therapy; 2) to determine the physiologic significance of the biochemical alterations; 3) continue to investigate the role of permissive factor(s) other than BP on MH both in vivo in different hypertensive rat models and in vitro in isolated myocytes, independent of BP or other mechanical effects. This study is expected to elucidate whether or not a fundamental alteration of the myocardial composition can occur as a result of longstanding hypertension which is a causal factor for reduced performance which may lead to failure of the heart and, more importantly, whether reversal of MH is beneficial or harmful and elucidate the involvement of humoral factor(s) responsible for development or reversal of MH. If excessive sympathetic stimulation by vasodilators, catecholamines or AII are proven to play a role in accentuating MH, reappraisal or modification of these therapeutic modalities is needed.
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