REGULATION OF CARDIAC HYPERTROPHY BY ANGIOTENSINS

肾素血管紧张素系统在血管紧张素系统的调节中起重要作用。 心血管、肾脏和内分泌功能。血管紧张素II可以 激活细胞内反应，包括钙动员， 刺激钠/氢交换，肌醇磷酸代谢， 二酰甘油生产、蛋白激酶C、Raf-1激酶 过度磷酸化，丝裂原激活的蛋白激酶级联， 核膜的磷酸化及其转录调控 即时和中间反应基因。最新发布的数据支持 这一概念认为，这种肽在代偿中发挥重要作用 与压力相关的左心室肥厚 超负荷和心肌梗死后的心室重构。 我们在体外和体内实验模型中获得的数据， 提示心脏内存在肾素血管紧张素系统，这可能 为这些回应做出贡献。最近的体外数据表明， 刺激各种信号转导通路和生长，在 对静态拉伸的反应，可能是由当地生产和 血管紧张素II的释放。我们将检验以下假设 机械牵张对心内肾素血管紧张素系统的调节 体液刺激和心内肾素的激活 血管紧张素系统是心脏疾病发生发展的前提 活体肥大。将在体外细胞中定义调节 使用机械和体液刺激的培养模型和体内使用 压力超负荷和心肌梗死的实验模型。 肾素血管紧张素系统的调节成分将被确定 使用药物抑制剂；中和抗体； 放射免疫分析.放射性标记受体结合.定量，多重， 逆转录聚合酶链式反应；原位杂交； 和免疫组织化学分析。个体肾素的贡献 血管紧张素系统成分将通过基因转移来确定 技术确定系统的重要性和运行机制 心内肾素血管紧张素系统的调节具有重要意义 对理解该系统的生物学作用的影响 与发育、生理和病理过程有关。 这些方向具有更广泛的应用，有助于 心血管疾病的成功管理。

The renin angiotensin system has a major role in the regulation of cardiovascular, renal and endocrine functions. Angiotensin II can activate intracellular responses including calcium mobilization, stimulation of sodium/hydrogen exchange, inositol phosphate metabolism, diacylglycerol production, protein kinase C, Raf-1 kinase hyperphosphorylation, the mitogen-activated protein kinase cascade, phosphorylation of nuclear lamina and transcriptional regulation of immediate and intermediate response genes. Recent published data support the concept that this peptide plays an important role in the compensatory left ventricular hypertrophy that occurs in association with pressure overload and in ventricular remodeling following myocardial infarction. Our data, obtained in both in vitro and in vivo experimental models, suggest that there is an intracardiac renin angiotensin system, which may contribute to these responses. Recent in vitro data indicate that stimulation of various signal transduction pathways and growth, in response to static stretch, may be mediated by local production and release of angiotensin II. We will test the hypotheses that the intracardiac renin angiotensin system is regulated by mechanical stretch and humoral stimuli and that activation of the intracardiac renin angiotensin system is a prerequisite for the development of cardiac hypertrophy in vivo. Regulation will be defined in an in vitro cell culture model using mechanical and humoral stimuli and in vivo using experimental models of pressure overload and myocardial infarction. Regulated components of the renin angiotensin system will be determined using pharmacological inhibitors; neutralizing antibodies; radioimmunoassay; radiolabeled receptor binding; quantitative, multiplex, reverse transcriptase polymerase chain reaction; in situ hybridization; and immunohistochemical analyses. The contribution of individual renin angiotensin system components will be determined utilizing gene transfer technology. Determining the importance of, and mechanisms by which an intracardiac renin angiotensin system is regulated has significant implications for understanding the biological role of this system in association with developmental, physiological and pathological processes. These directions have the broader application of contributing to the successful management of cardiovascular disease.