Renal Transporter Activation During Angiotensin-II Hypertension is Blunted in Interferon-γ−/− and Interleukin-17A−/− Mice. Issue 3 (March 2015)

• Record Type: Journal Article
• Authors: Kamat, Nikhil V.; Thabet, Salim R.; Xiao, Liang; Saleh, Mohamed A.; Kirabo, Annet; Madhur, Meena S.; Delpire, Eric; Harrison, David G.; McDonough, Alicia A.
• Is Part Of: Hypertension. Volume 65:Issue 3(2015:Mar.)
• Publication Date: 2015-03
• Subjects: angiotensin-II -- cytokines -- epithelial Na+ channel -- NHE3 protein -- NKCC2 protein sodium chloride cotransporters -- SPAK protein; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.114.04975
• Languages: English
• ISSNs: 0194-911X

Abstract

Abstract : Ample genetic and physiological evidence establishes that renal salt handling is a critical regulator of blood pressure. Studies also establish a role for the immune system, T-cell infiltration, and immune cytokines in hypertension. This study aimed to connect immune cytokines, specifically interferon-γ (IFN-γ) and interleukin-17A (IL-17A), to sodium transporter regulation in the kidney during angiotensin-II (Ang-II) hypertension. C57BL/6J (wild-type) mice responded to Ang-II infusion (490 ng/kg per minute, 2 weeks) with a rise in blood pressure (170 mm Hg) and a significant decrease in the rate of excretion of a saline challenge. In comparison, mice that lacked the ability to produce either IFN-γ (IFN-γ −/− ) or IL-17A (IL-17A −/− ) exhibited a blunted rise in blood pressure (<150 mm Hg), and both the genotypes maintained baseline diuretic and natriuretic responses to a saline challenge. Along the distal nephron, Ang-II infusion increased abundance of the phosphorylated forms of the Na-K-2Cl cotransporter, Na-Cl cotransporter, and Ste20/SPS-1–related proline-alanine–rich kinase, in both the wild-type and the IL-17A −/− but not in IFN-γ −/− mice; epithelial Na channel abundance increased similarly in all the 3 genotypes. In the proximal nephron, Ang-II infusion significantly decreased abundance of Na/H-exchanger isoform 3 and the motor myosin VI in IL-17A −/− and IFN-γ −/−, but not in wild-type; the Na-phosphate cotransporter decreased in all the 3 genotypes. Our results suggest that during Ang-II hypertension both IFN-γ and IL-17A production interfere with the pressure natriuretic decrease in proximal tubule sodium transport and that IFN-γ production is necessary to activate distal sodium reabsorption. Abstract : Supplemental Digital Content is available in the text.