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[肾脏中的肾上腺髓质素:生理学与病理生理学]

[Adrenomedullin in the kidney: physiology and pathophysiology].

作者信息

Sogbe-Díaz Miguel Eduardo, Díaz-López Emilia Elena

出版信息

Invest Clin. 2016 Mar;57(1):66-76.

Abstract

Adrenomedullin (AM) is a potent vasodilatory 52-aminoacid peptide hormone, ubiquitous with multiple physiological effects which contribute to homeostatic responses. Significantly, it is distributed in the adrenal gland, lung, cardiovascular and renal system. The biological effects of AM are directly mediated by specific receptors as heterodimers composed of the calcitonin-receptor-like receptor (CLR) and one of two receptor activity modifying proteins (RAMP2 or RAMP3). The CLR/RAMP2 (AM1 receptor) is more highly AM-specific than The CLR/RAMP3 (AM2 receptor). Plasma levels of AM are elevated proportionately to the increase in blood pressure and degree of renal damage in patients with hypertension; likewise, these levels are correlated with the degree ofheart and arterial hypertrophy. AM has renal vasodilatory, natriuretic and diuretic actions; increased glomerular filtration rate and renal blood flow. AM inhibits proliferation and reactive oxygen species generation in mesangial cells; also inhibits aldosterone secretion in the zona glomerulosa and endothelin-1 in vascular smooth muscle cells. Therefore, it is proposed as a new marker in various diseases, especially chronic renal failure. This disease presents compensatory hypertrophy of the glomeruli and mesangial proliferation, administration of AM reduces the levels of proteinuria, suggesting that AM has an important modulator role in blood pressure and could be a therapeutic option for chronic renal failure.

摘要

肾上腺髓质素(AM)是一种具有强大血管舒张作用的52个氨基酸的肽类激素,广泛存在且具有多种生理效应,有助于维持体内稳态反应。值得注意的是,它分布于肾上腺、肺、心血管和肾脏系统。AM的生物学效应由特定受体直接介导,这些受体是由降钙素受体样受体(CLR)和两种受体活性修饰蛋白(RAMP2或RAMP3)之一组成的异二聚体。CLR/RAMP2(AM1受体)比CLR/RAMP3(AM2受体)对AM的特异性更高。高血压患者血浆AM水平与血压升高和肾损伤程度成比例升高;同样,这些水平与心脏和动脉肥厚程度相关。AM具有肾血管舒张、利钠和利尿作用;可增加肾小球滤过率和肾血流量。AM抑制系膜细胞增殖和活性氧生成;还抑制肾小球球状带醛固酮分泌以及血管平滑肌细胞中内皮素-1的分泌。因此,它被提议作为各种疾病尤其是慢性肾衰竭的新标志物。这种疾病表现为肾小球代偿性肥大和系膜增生,给予AM可降低蛋白尿水平,表明AM在血压调节中具有重要作用,可能是慢性肾衰竭的一种治疗选择。

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