Premium
Inhibition of AT2R and BK2R attenuates the effect of high K intake (HK) on thiazide‐sensitive Na‐Cl cotransporter
Author(s) -
Zhang Dandan,
Gu Li,
Wu Peng,
Gao Zhongxizi,
Gu Ruimin,
Lin Daohong,
Wang Wenhui
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.824.23
Subject(s) - endocrinology , medicine , distal convoluted tubule , chemistry , stimulation , cotransporter , antagonist , symporter , reabsorption , receptor , kidney , sodium , biochemistry , transporter , organic chemistry , gene
The basolateral K channel composed of Kir4.1/Kir5.1 in the distal convoluted tubule (DCT) plays a key role in mediating the inhibitory effect of high dietary K (HK) intake on NCC activity by inhibiting the basolateral K conductance and depolarizing DCT membrane potential. Previous studies have demonstrated that the stimulation of type II angiotensin II receptor (AT2R) or bradykinin type II receptor (BK2R) inhibited the basolateral K channels in the DCT. Furthermore, the inhibition of AT2R or BK2R impairs renal K excretion by stimulating the expression of total NCC (tNCC) and phorsphor‐NCC (pNCC). This effect was induced by stimulation of the basolateral K channels because neither PD123319 (AT2R antagonist) nor HOE140 (BK2R antagonist) had a significant effect on NCC in kidney‐specific Kir4.1 knockout mice (Ks‐Kir4.1 KO). The aim of the present study is to test whether the activation of both AT2R and BK2R are required for mediating the effect of HK intake on the basolateral K channels and NCC. Feeding mice (male and female) with HK diet (2% or 10%) for overnight significantly decreased the basolateral K conductance, depolarized the DCT membrane, diminished the expression of pNCC and tNCC and decreased thiazide‐sensitive natriuresis. The deletion of Kir4.1 not only decreases the NCC activity but also abolishes the effect of overnight‐HK diet on NCC. Pretreatment of the mice with PD123319 and HOE140 stimulates the expression of both tNCC and pNCC. Moreover, the overnight HK‐induced stimulation of NCC expression was significantly attenuated in the mice pretreated with PD123319 and HOE140. In contrast, HK diet (overnight) still decreased the expression of both tNCC and pNCC in the mice pretreated with PD123319 alone. We conclude that synergistic activation of AT2R and BK2R is required for the effect of overnight HK diet on NCC activity. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .