Unknown

Dataset Information

0

Proximal Tubule-Specific Deletion of the NHE3 (Na+/H+ Exchanger 3) in the Kidney Attenuates Ang II (Angiotensin II)-Induced Hypertension in Mice.


ABSTRACT: The present study directly tested the hypothesis that the NHE3 (Na+/H+ exchanger 3) in the proximal tubules of the kidney is required for the development of Ang II (angiotensin II)-induced hypertension using PT-Nhe3-/- (proximal tubule-specific NHE3 knockout) mice. Specifically, PT-Nhe3-/- mice were generated using the SGLT2-Cre/Nhe3loxlox approach, whereas Ang II-induced hypertension was studied in 12 groups (n=5-12 per group) of adult male and female wild-type (WT) and PT-Nhe3-/- mice. Under basal conditions, systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were significantly lower in male and female PT-Nhe3-/- than WT mice (P<0.01). A high pressor, 1.5 mg/kg per day, intraperitoneal or a slow pressor dose of Ang II, 0.5 mg/kg per day, intraperitoneal for 2 weeks significantly increased systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure in male and female WT mice (P<0.01), but the hypertensive response to Ang II was markedly attenuated in male and female PT-Nhe3-/- mice (P<0.01). Ang II impaired the pressure-natriuresis response in WT mice, whereas proximal tubule-specific deletion of NHE3 improved the pressure-natriuresis response in Ang II-infused PT-Nhe3-/- mice (P<0.01). AT1 receptor blocker losartan completely blocked Ang II-induced hypertension in both WT and PT-Nhe3-/- mice (P<0.01). However, inhibition of nitric oxide synthase with L-NG-Nitroarginine methyl ester had no effect on Ang II-induced hypertension in WT or PT-Nhe3-/- mice (not significant). Furthermore, Ang II-induced hypertension was significantly attenuated by an orally absorbable NHE3 inhibitor AVE0657. In conclusion, NHE3 in the proximal tubules of the kidney may be a therapeutical target in hypertension induced by Ang II or with increased NHE3 expression in the proximal tubules.

SUBMITTER: Li XC 

PROVIDER: S-EPMC6685743 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

Proximal Tubule-Specific Deletion of the NHE3 (Na<sup>+</sup>/H<sup>+</sup> Exchanger 3) in the Kidney Attenuates Ang II (Angiotensin II)-Induced Hypertension in Mice.

Li Xiao C XC   Zhu Dongmin D   Chen Xu X   Zheng Xiaowen X   Zhao Chunling C   Zhang Jianfeng J   Soleimani Manoocher M   Rubera Isabelle I   Tauc Michel M   Zhou Xinchun X   Zhuo Jia L JL  

Hypertension (Dallas, Tex. : 1979) 20190729 3


The present study directly tested the hypothesis that the NHE3 (Na<sup>+</sup>/H<sup>+</sup> exchanger 3) in the proximal tubules of the kidney is required for the development of Ang II (angiotensin II)-induced hypertension using PT-Nhe3<sup>-/-</sup> (proximal tubule-specific NHE3 knockout) mice. Specifically, PT-Nhe3<sup>-/-</sup> mice were generated using the SGLT2-Cre/Nhe3<sup>loxlox</sup> approach, whereas Ang II-induced hypertension was studied in 12 groups (n=5-12 per group) of adult male  ...[more]

Similar Datasets

| S-EPMC6309803 | biostudies-literature
| S-EPMC7289683 | biostudies-literature
| S-EPMC9560057 | biostudies-literature
| S-EPMC3234923 | biostudies-literature
| S-EPMC7299167 | biostudies-literature
| S-EPMC5898891 | biostudies-literature
| S-EPMC4588303 | biostudies-literature
| S-EPMC6485378 | biostudies-literature
| S-EPMC3197336 | biostudies-literature
| S-EPMC2234495 | biostudies-literature