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

心脏肥厚是动脉性高血压的常见并发症，但其发病机制尚不清楚。既往研究提示高血压左室肥厚是心脏对后负荷增加的适应性代偿反应，肥厚程度与高血压的严重程度直接相关。然而，最近的广泛研究表明，并非所有病例都是如此，并且根据高血压的类型，引发和发展心脏肥厚的因素有所不同。最近的研究也表明，除了儿茶酚胺和肾素-血管紧张素II外，一些体液因素可能有助于心脏肥厚的发生。因此，在本研究中，我们研究了在Page法诱导的肾周性高血压中存在诱导和/或调节心脏肥厚的体液因子的可能性。因此，我们首先利用培养的大鼠心脏细胞建立了这种微量检测系统。当使用儿茶酚胺来研究这种检测系统的实用性时，这种检测系统被发现对这种目的非常有用。儿茶酚胺是众所周知的诱导心脏肥厚的物质。血管紧张素II在器官肥大中的潜在作用是近年来心血管疾病研究的热点之一。我们目前的研究表明血管紧张素II可以直接作用于培养的心脏细胞，从而刺激培养的大鼠心脏细胞的蛋白质代谢。本研究的主要目的是探讨是否存在某种体液因子引起犬肾周性高血压的心肌肥厚。我们的研究结果表明，从肥厚的左心室提取的心脏提取物可以增加^ 3h -尿苷和^<14> c -亮氨酸在培养的心脏细胞中的摄取。通过凝胶过滤技术和高效液相色谱系统对该因子进行部分纯化后，我们还发现一个分子量约为11200的分子具有刺激培养心脏细胞蛋白质代谢的能力。此外，我们的初步结果表明，该因子是热不稳定的，并且该因子在蛋白水解酶，胰蛋白酶处理后失去了活性，从而表明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，但它可能控制参与心肌肥厚发展的生化事件。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厚的病理生理作用。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