Renal transporter activation during angiotensin-II hypertension is blunted in interferon-?-/- and interleukin-17A-/- mice.

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-? (IFN-?) 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-? (IFN-?(-/-)) 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-?(-/-) 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-?(-/-), 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-? and IL-17A production interfere with the pressure natriuretic decrease in proximal tubule sodium transport and that IFN-? production is necessary to activate distal sodium reabsorption.

SUBMITTER: Kamat NV 

PROVIDER: S-EPMC4326622 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature