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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Angiotensin Ⅱ causes hypertension and cardiac hypertrophy through its receptors in the kidney
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Angiotensin Ⅱ causes hypertension and cardiac hypertrophy through its receptors in the kidney

机译:血管紧张素Ⅱ通过肾脏中的受体引起高血压和心脏肥大

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Essential hypertension is a common disease, yet its pathogenesis is not well understood. Altered control of sodium excretion in the kidney may be a key causative feature, but this has been difficult to test experimentally, and recent studies have challenged this hypothesis. Based on the critical role of the renin-angiotensin system (RAS) and the type Ⅰ (AT_1) angiotensin receptor in essential hypertension, we developed an experimental model to separate AT_1 receptor pools in the kidney from those in all other tissues. Although actions of the RAS in a variety of target organs have the potential to promote high blood pressure and end-organ damage, we show here that angiotensin Ⅱ causes hypertension primarily through effects on AT_1 receptors in the kidney. We find that renal AT_1 receptors are absolutely required for the development of angiotensin Ⅱ-dependent hypertension and cardiac hypertrophy. When AT_1 receptors are eliminated from the kidney, the residual repertoire of systemic, extrarenal AT_1 receptors is not sufficient to induce hypertension or cardiac hypertrophy. Our findings demonstrate the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications. Further, they suggest that the major mechanism of action of RAS inhibitors in hypertension is attenuation of angiotensin Ⅱ effects in the kidney.
机译:原发性高血压是一种常见疾病,但其发病机理尚不清楚。肾脏中钠排泄控制的改变可能是一个关键的病因,但这很难通过实验进行检验,最近的研究挑战了这一假设。基于肾素-血管紧张素系统(RAS)和Ⅰ型(AT_1)血管紧张素受体在原发性高血压中的关键作用,我们建立了一个实验模型,将肾脏中的AT_1受体库与其他所有组织分离。尽管RAS在多种靶器官中的作用有促进高血压和终末器官损害的潜力,但我们在这里表明血管紧张素Ⅱ主要通过对肾脏AT_1受体的作用引起高血压。我们发现肾脏AT_1受体是血管紧张素Ⅱ依赖性高血压和心脏肥大的发展所必需的。当AT_1受体从肾脏中清除后,全身性肾外AT_1受体的残留组成不足以诱发高血压或心脏肥大。我们的发现证明了肾脏在高血压及其心血管并发症的发病机制中的关键作用。此外,他们认为RAS抑制剂在高血压中的主要作用机制是减弱血管紧张素Ⅱ在肾脏中的作用。

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