REVERSAL OF MYOCARDIAL HYPERTROPHY IN HYPERTENSION

我们实验室的研究表明， 或逆转心肌肥厚（MH）不能解释为 血压（BP）水平的变化。 抗高血压药物 治疗表明，除了血压控制，肾上腺素能系统 可能在逆转MH中发挥重要作用。 我们已经表明，MH是一个 胶原和非胶原蛋白增加的结果。 一 对胶原蛋白的详细研究表明浓度增加， 6月龄SHR胶原合成率、胶原含量与 胶原蛋白表型发生了显著变化，所有这些都可能是 通过抗高血压治疗预防。 虽然体内研究表明 β-肾上腺素能系统参与肥大的逆转， 我们的初步数据使用离体心肌细胞（独立于BP 和血流动力学变化）证实存在体液因素 刺激了蛋白质合成。 所有这些 观察结果促使我们继续进行调查，目的如下： 1)研究心肌收缩力和心肌收缩力的可能的根本变化， 心脏成分（肌球蛋白、其ixozyme和Ca++ ATP酶）和胶原 表型模式的MH在响应压力，如 长期高血压，并在其逆转或预防后， 抗高血压药物治疗; 2）确定生理意义 的生化改变; 3）继续调查的作用， 在不同的体内模型中，除BP外的容许因素对MH的影响 高血压大鼠模型和体外分离的心肌细胞，独立于 BP或其他机械效应。 这项研究有望阐明 心肌成分的根本改变是否 长期高血压的结果，这是一个因果因素， 性能下降，可能导致心力衰竭， 重要的是，MH逆转是有益的还是有害的， 参与体液因素负责发展或 逆转MH。 如果血管扩张剂过度刺激交感神经， 儿茶酚胺或AII被证明在加重MH中起作用， 需要重新评估或修改这些治疗方式。

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.