STUDY OF HUMORAL FACTOR(S) FOR CARDIAC HYPERTROPHY IN EXPERIMENTAL PERINEPHRITIC HYPERTENSION IN DOGS

心肌肥厚是动脉高压的常见并发症，但其发病机制尚不清楚。以往的研究表明，高血压左室肥厚是心脏对后负荷增加的一种适应性和代偿性反应，肥厚的程度与高血压的严重程度直接相关。然而，最近广泛的研究表明，这并不是在所有情况下都是正确的，并且启动和发展心脏肥大的因素根据高血压的类型而不同。最近的研究也表明，一些体液因素以外的儿茶酚胺和肾素-血管紧张素II可能有助于心肌肥厚的发展。因此，在本研究中，我们调查的可能性存在的体液因子诱导和/或调节心脏肥大的肾周高血压的Page方法。为了研究这些体液因子，一个微量测定系统， ...更多信息 因此，我们首先利用培养的大鼠心肌细胞建立了这一检测体系。当通过使用众所周知可诱导心脏肥大的儿茶酚胺来研究该测定系统的有用性时，发现该测定系统对于该目的非常有用。血管紧张素II对器官肥大的潜在作用是近年来心血管疾病研究的热点之一。本研究表明，血管紧张素II可直接作用于培养的大鼠心肌细胞，从而刺激心肌细胞的蛋白质代谢。本研究的主要目的是探讨肾周高血压时是否存在引起心肌肥厚的体液因素。我们的研究结果表明，从肾周高血压的肥厚左心室中提取的心脏提取物可增加培养的心脏细胞对^3 H-尿苷和^<14>C-亮氨酸的摄取。通过凝胶过滤技术和HPLC系统部分纯化该因子后，我们还发现分子量约为11200的分子具有刺激培养的心脏细胞的蛋白质代谢的能力。初步结果表明，该因子是热不稳定的，经蛋白水解酶胰蛋白酶处理后失去活性，提示该因子可能是一种肽或蛋白质。这种调节因子的病理生理作用尚不清楚，但它可能控制心肌肥大发展中的生化事件。我们现在正试图进一步纯化和表征这种刺激因子，并阐明其在高血压模型中心脏肥大的病理生理作用。少

Cardiac hypertrophy is a commom complication of arterial hypertension, but its pathogenesis is not well understood. Previous studies have suggested that left ventricular hypertrophy in hypertension is an adaptive and compensatory response by the heart to increased afterload and that the extent of hypertrophy can be directly correlated with the severity of hypertension. However, recent extensive studies have revealed that this is not true in all cases, and that factors which initiate and develop cardiac hypertrophy differ according to the type of hypertension. Recent studies also have suggested that some humoral factors other than catecholamine and renin-angiotensin II may contribute to the development of cardiac hypertrophy. In the present study, therefore, we investigated the possibility of the existence of humoral factor(s) which induce and/or modulate cardiac hypertrophy in perinephritic hypertension induced by the Page method. To investigate such humoral factors, a microassay syste … More m inevitably necessary, so we established such assay system using cultured rat heart cells at first. When the usefulness of this assay system was investigated by using catecholamine which is well known to induce cardiac hypertrophy, this assay system was found to be very useful for such purpose. The potential ability of angiotensin II for organ hypertrophy is one of the recent topic of cardiovascular diseases. Our present study revealed that angiotensin II can directly act on cultured heart cells, thereby stimulates protein metabolism of cultured rat heart cells. The main purpose of this study was to investigate whether or not there exists some humoral factor(s) which induce cardiac hypertrophy in perinephritic hypertension in dogs. Our results in the present study showed that heart extract obtained from hypertrophied, left ventricle of perinephritic hypertension in dogs increased the uptake of ^3H-uridine and ^<14>C-leucine into cultured heart cells. After partial purification of this factor by a gel filtration technique and a HPLC system, we also found that a molecule with molecular weight about 11200 has an ability to stimulate protein metabolism of cultured heart cells. Furthermore our preliminary results suggest that thi factor is heat labile and that the activity of this factor has been lost after treatment with proteolytic enzyme, trypsin, thereby suggesting that this factor may be a kind of peptide or protein. The pathophysiological role of this stumulatory factor is still unknown, but it may control biochemical events involved in the development of cardiac hypertrophy. We are now attempting to further purify and characterize this stimulatory factor and shed light on its pathophysiological role in cardiac hypertrophy in this model of hypertension. Less