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The renal and blood pressure response to low sodium diet in P2X4 receptor knockout mice

Craigie, E; Menzies, RI; Larsen, CK; Jacquillet, G; Carrel, M; Wildman, SS; Loffing, J; ... Unwin, RJ; + view all (2018) The renal and blood pressure response to low sodium diet in P2X4 receptor knockout mice. Physiological Reports , 6 (19) , Article e13899. 10.14814/phy2.13899. Green open access

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Abstract

In the kidney, purinergic (P2) receptor-mediated ATP signaling has been shown to be an important local regulator of epithelial sodium transport. Appropriate sodium regulation is crucial for blood pressure (BP) control and disturbances in sodium balance can lead to hypo- or hypertension. Links have already been established between P2 receptor signaling and the development of hypertension, attributed mainly to vascular and/or inflammatory effects. A transgenic mouse model with deletion of the P2X4 receptor (P2X4-/- ) is known to have hypertension, which is thought to reflect endothelial dysfunction and impaired nitric oxide (NO) release. However, renal function in this model has not been characterized; moreover, studies in vitro have shown that the P2X4 receptor can regulate renal epithelial Na+ channel (ENaC) activity. Therefore, in the present study we investigated renal function and sodium handling in P2X4-/- mice, focusing on ENaC-mediated Na+ reabsorption. We confirmed an elevated BP in P2X4-/- mice compared with wild-type mice, but found that ENaC-mediated Na+ reabsorption is no different from wild-type and does not contribute to the raised BP observed in the knockout. However, when P2X4-/- mice were placed on a low sodium diet, BP normalized. Plasma aldosterone concentration tended to increase according to sodium restriction status in both genotypes; in contrast to wild-types, P2X4-/- mice did not show an increase in functional ENaC activity. Thus, although the increased BP in P2X4-/- mice has been attributed to endothelial dysfunction and impaired NO release, there is also a sodium-sensitive component.

Type: Article
Title: The renal and blood pressure response to low sodium diet in P2X4 receptor knockout mice
Open access status: An open access version is available from UCL Discovery
DOI: 10.14814/phy2.13899
Publisher version: https://doi.org/10.14814/phy2.13899
Language: English
Additional information: Copyright © 2018 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: ENaC, hypertension, purinergic, purinoceptor, salt-sensitivity, sodium
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10066501
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