内分泌学
肾素-血管紧张素系统
内科学
醛固酮
盐皮质激素受体
上皮钠通道
尿钠
化学
血管紧张素Ⅱ受体1型
受体
盐皮质激素
入球微动脉
肾
血浆肾素活性
肾单位
血管紧张素II
生物
钠
医学
血压
有机化学
作者
Ziwei Fu,Huaqing Zheng,Kannaree Kaewsaro,Jacob Lambert,Yanting Chen,Tianxin Yang
出处
期刊:American Journal of Physiology-renal Physiology
[American Physiological Society]
日期:2022-10-27
卷期号:324 (1): F1-F11
标识
DOI:10.1152/ajprenal.00088.2022
摘要
Soluble (pro)renin receptor (sPRR), the extracellular domain of (pro)renin receptor (PRR), is primarily generated by site-1 protease and furin. It has been reported that sPRR functions as an important regulator of intrarenal renin contributing to angiotensin II (ANG II)-induced hypertension. Relatively, less is known for the function of sPRR in ANG II-independent hypertension such as mineralocorticoid excess. In the present study, we used a novel mouse model with mutagenesis of the cleavage site in PRR (termed as PRRR279V/L282V or mutant) to examine the phenotype during aldosterone (Aldo)-salt treatment. The hypertensive response of mutant mice to Aldo-salt treatment was blunted in parallel with the attenuated response of plasma volume expansion and renal medullary α-epithelial Na+ channel expression. Moreover, Aldo-salt-induced hypertrophy in the heart and kidney as well as proteinuria were improved, accompanied by blunted polydipsia and polyuria. Together, these results represent strong evidence favoring endogenous sPRR as a mediator of Aldo-salt-induced hypertension and renal injury.NEW & NOTEWORTHY We used a novel mouse model with mutagenesis of the cleavage site of PRR to support soluble PRR as an essential mediator of aldosterone-salt-induced hypertension and also as a potential therapeutic target for patients with mineralocorticoid excess. We firstly report that soluble PRR-dependent pathway medicates the Na+-retaining action of aldosterone in the distal nephron, which opens up a new area for a better understanding of the molecular basis of renal handling of Na+ balance and blood pressure.
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