title: High potassium promotes mutual interaction between (pro)renin receptor and the local renin-angiotensin-aldosterone system in rat inner medullary collecting duct cells.
abstract: (Pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD) with unclear functional implication. It is not known whether CD PRR is regulated by high potassium (HK). Here, we aimed to investigate the effect of HK on PRR expression and its role in regulation of aldosterone synthesis and release in the CD. In primary rat inner medullary CD cells, HK augmented PRR expression and soluble PPR (sPRR) release in a time- and dose-dependent manner, which was attenuated by PRR small interfering RNA (siRNA), eplerenone, and losartan. HK upregulated aldosterone release in parallel with an increase of CYP11B2 (cytochrome P-450, family 11, subfamily B, polypeptide 2) protein expression and upregulation of medium renin activity, both of which were attenuated by a PRR antagonist PRO20, PRR siRNA, eplerenone, and losartan. Similarly, prorenin upregulated aldosterone release and CYP11B2 expression, both of which were attenuated by PRR siRNA. Interestingly, a recombinant sPRR (sPRR-His) also stimulated aldosterone release and CYP11B2 expression. Taken together, we conclude that HK enhances a local renin-angiotensin-aldosterone system (RAAS), leading to increased PRR expression, which in turn amplifies the response of the RAAS, ultimately contributing to heightened aldosterone release.
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China; and.
authors.forename: Chuanming
authors.initials: C
authors.lastname: Xu
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China; and.
authors.forename: Hui
authors.initials: H
authors.lastname: Fang
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China; and.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China; and.
authors.forename: Aihua
authors.initials: A
authors.lastname: Lu
authors.affiliation: Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, China; and Tianxin.Yang@hsc.utah.edu.|Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D019405:Cytochrome P-450 CYP11B2 / Q000494:pharmacology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D011956:Receptors, Cell Surface; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D012083:Renin; D019808:Losartan; D011188:Potassium
keywords: (pro)renin receptor; CYP11B2; and aldosterone; inner medullary collecting duct; potassium