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Am J Physiol Renal Physiol. 2017 Aug 1;313(2):F505-F513. doi: 10.1152/ajprenal.00087.2017. Epub 2017 May 31.

Gender difference in kidney electrolyte transport. I. Role of AT1a receptor in thiazide-sensitive Na+-Cl- cotransporter activity and expression in male and female mice.

Author information

1
Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut.
2
Department of Basic Medical Science, Chengdu Medical College, Chengdu, China.
3
Department of Physiology and Biophysics, Weill Medical College of Cornell University, Ithaca, New York; and.
4
Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut; tong.wang@yale.edu.

Abstract

We studied gender differences in Na+-Cl- cotransporter (NCC) activity and expression in wild-type (WT) and AT1a receptor knockout (KO) mice. In renal clearance experiments, urine volume (UV), glomerular filtration rate, absolute Na+ (ENa) and K+ (EK), and fractional Na+ (FENa) and K+ excretion were measured and compared at peak changes after bolus intravenous injection of hydrochlorothiazide (HCTZ; 30 mg/kg). In WT, females responded more strongly than males to HCTZ, with larger fractional increases of UV (7.8- vs. 3.4-fold), ENa (11.7- vs. 5.7-fold), FENa (7.9- vs. 4.9-fold), and EK (2.8- vs. 1.4-fold). In contrast, there were no gender differences in the responses to the diuretic in KO mice; HCTZ produced greater effects on male KO than on WT but similar effects on females. In WT, total (tNCC) and phosphorylated (pNCC) NCC protein expressions were 1.8- and 4.6-fold higher in females compared with males (P < 0.05), consistent with the larger response to HCTZ. In KO mice, tNCC and pNCC increased significantly in males to levels not different from those in females. There were no gender differences in the expression of the Na+/H+ exchanger (NHE3) in WT; NHE3 protein decreased to similar extents in male and female KO animals, suggesting AT1a-mediated NHE3 expression in proximal tubules. The resulting increase in delivery of NaCl to the distal nephron may underlie increased NCC expression and activity in mice lacking the AT1a receptor.

KEYWORDS:

angiotensin II; angiotensin type 1a receptor; gender differences; knockout; sodium-chloride cotransporter; urinary sodium and potassium excretion; wild-type

PMID:
28566500
PMCID:
PMC5582908
[Available on 2018-08-01]
DOI:
10.1152/ajprenal.00087.2017
[Indexed for MEDLINE]
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