Renal (tissue) kallikrein-kinin system in the kidney and novel potential drugs for salt-sensitive hypertension.

Makoto Katori, Masataka Majima
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引用次数: 13

Abstract

A large variety of antihypertensive drugs, such as angiotensin converting enzyme inhibitors, diuretics, and others, are prescribed to hypertensive patients, with good control of the condition. In addition, all individuals are generally believed to be salt sensitive and, thus, severe restriction of salt intake is recommended to all. Nevertheless, the physiological defense mechanisms in the kidney against excess salt intake have not been well clarified. The present review article demonstrated that the renal (tissue) kallikrein-kinin system (KKS) is ideally situated within the nephrons of the kidney, where it functions to inhibit the reabsorption of NaCl through the activation of bradykinin (BK)-B2 receptors localized along the epithelial cells of the collecting ducts (CD). Kinins generated in the CD are immediately inactivated by two kidney-specific kinin-inactivating enzymes (kininases), carboxypeptidase Y-like exopeptidase (CPY), and neutral endopeptidase (NEP). Our work demonstrated that ebelactone B and poststatin are selective inhibitors of these kininases. The reduced secretion of the urinary kallikrein is linked to the development of salt-sensitive hypertension, whereas potassium ions and ATP-sensitive potassium channel blockers ameliorate salt-sensitive hypertension by accelerating the release of renal kallikrein. On the other hand, ebelactone B and poststatin prolong the life of kinins in the CD after excess salt intake, thereby leading to the augmentation of natriuresis and diuresis, and the ensuing suppression of salt-sensitive hypertension. In conclusion, accelerators of the renal kallikrein release and selective renal kininase inhibitors are both novel types of antihypertensive agents that may be useful for treatment of salt-sensitive hypertension.

肾(组织)钾化钾素-激肽系统及治疗盐敏感性高血压的新药物。
高血压患者服用多种抗高血压药物,如血管紧张素转换酶抑制剂、利尿剂等,病情得到很好的控制。此外,一般认为所有人都对盐敏感,因此建议所有人严格限制盐的摄入量。然而,肾脏对过量盐摄入的生理防御机制尚未得到很好的阐明。本综述表明,肾(组织)缓激肽-激肽系统(KKS)理想地位于肾脏的肾单位内,它通过激活位于集管上皮细胞(CD)沿线的缓激肽(BK)-B2受体来抑制NaCl的重吸收。在CD中产生的激肽被两种肾特异性激肽灭活酶(激肽酶),羧基肽酶y样外肽酶(CPY)和中性内肽酶(NEP)立即灭活。我们的研究表明依贝拉内酯B和后他汀是这些激酶的选择性抑制剂。尿钾激肽的分泌减少与盐敏感性高血压的发展有关,而钾离子和atp敏感的钾通道阻滞剂通过加速肾钾激肽的释放来改善盐敏感性高血压。另一方面,依曲内酯B和后他汀可延长过量盐摄入后CD中激肽的寿命,从而导致尿钠和利尿作用增强,进而抑制盐敏感性高血压。总之,肾激肽释放促进剂和选择性肾激肽酶抑制剂都是新型的抗高血压药物,可能对治疗盐敏感性高血压有用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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