Renal Tubule Angiotensin II Type 1 Receptor–Associated Protein Promotes Natriuresis and Inhibits Salt‐Sensitive Blood Pressure Elevation

Mar 21, 2015Journal of the American Heart Association

A kidney protein linked to salt balance helps reduce salt-related high blood pressure

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Abstract

Renal ATRAP transgenic mice showed suppressed blood pressure elevation during high salt loading compared to wild-type mice.

Sodium handling and blood pressure regulation were assessed in response to high salt intake in mice.
Urinary sodium excretion was significantly enhanced in renal ATRAP transgenic mice during high salt loading.
Blood pressure elevation due to high salt intake was inhibited in transgenic mice despite similar baseline levels.
Renal angiotensin II levels remained comparable between transgenic and wild-type mice under both normal and high salt conditions.
Decreased plasma membrane expression of the angiotensin II type 1 receptor was observed in transgenic mice.

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BACKGROUND: Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP; Agtrap gene) promotes AT1R internalization along with suppression of pathological AT1R activation. In this study, we examined whether enhancement of ATRAP in the renal distal tubules affects sodium handling and blood pressure regulation in response to high salt (HS) loading, using ATRAP transgenic mice on a salt-sensitive C57BL/6J background.

METHODS AND RESULTS: Renal ATRAP transgenic (rATRAP-Tg) mice, which exhibit renal tubule-dominant ATRAP enhancement, and their wild-type littermate C57BL/6J mice on a normal salt diet (0.3% NaCl) at baseline were subjected to dietary HS loading (4% NaCl) for 7 days. In rATRAP-Tg mice, the dietary HS loading-mediated blood pressure elevation was suppressed compared with wild-type mice, despite similar baseline blood pressure. Although renal angiotensin II level was comparable in rATRAP-Tg and wild-type mice with and without HS loading, urinary sodium excretion in response to HS loading was significantly enhanced in the rATRAP-Tg mice. In addition, functional transport activity of the amiloride-sensitive epithelial Na(+) channel was significantly decreased under saline volume-expanded conditions in rATRAP-Tg mice compared with wild-type mice, without any evident change in epithelial Na(+) channel protein expression. Plasma membrane AT1R expression in the kidney of rATRAP-Tg mice was decreased compared with wild-type mice.

CONCLUSIONS: These results demonstrated that distal tubule-dominant enhancement of ATRAP inhibits pathological renal sodium reabsorption and blood pressure elevation in response to HS loading. The findings suggest that ATRAP-mediated modulation of sodium handling in renal distal tubules could be a target of interest in salt-sensitive blood pressure regulation.

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Renal Tubule Angiotensin II Type 1 Receptor–Associated Protein Promotes Natriuresis and Inhibits Salt‐Sensitive Blood Pressure Elevation

Abstract

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