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Aldosterone‐Induced Hypertension is T Lymphocyte‐Dependent and Attenuated by Activation of the G Protein‐Coupled Estrogen Receptor 1
Author(s) -
Dinh Quynh Nhu,
Vinh Antony,
Kim Hyun Ah,
Diep Henry,
Broughton Bradley,
Chrissobolis Sophocles,
Drummond Grant,
Sobey Christopher
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.718.14
Subject(s) - aldosterone , endocrinology , medicine , gper , mineralocorticoid receptor , chemistry , blood pressure , mineralocorticoid , agonist , receptor , estrogen receptor , estrogen , cancer , breast cancer
The G protein‐coupled estrogen receptor 1 (GPER), a membrane‐localised estrogen receptor, may modulate some of the effects of aldosterone. G‐1, a GPER agonist, can promote T cell‐mediated anti‐inflammatory actions and acutely lower blood pressure. This study aimed to test the effects of G‐1 and G‐15 (GPER antagonist) on aldosterone‐induced hypertension in male and female mice, and to examine the cellular mechanisms involved. C57Bl6 and RAG1‐deficient mice were treated with vehicle, aldosterone/salt (0.72 mg/kg/d SC plus 0.9% NaCl for drinking) ± G‐1 (0.03 mg/kg/d SC) and/or G‐15 (0.3 mg/kg/d SC) for 14 d. Some females were ovariectomised 7 d prior to treatment. T cells were adoptively transferred via IV injections 21 d prior to treatment. In males, aldosterone/salt caused a sustained increase in blood pressure of ~25 mmHg within 7 d and this increase was attenuated by ~50% in the presence of G‐1 (n=11–13, P<0.05). G‐15 alone did not alter hypertension caused by aldosterone/salt but it prevented the anti‐hypertensive effect of G‐1. By contrast, the pressor response to aldosterone/salt was delayed in females where an increase in blood pressure was only observed at 14 d; however co‐administration of aldosterone/salt with G‐15 resulted in a marked increase of ~20 mmHg from 7 d (n=6–8, P<0.05). Administration of aldosterone/salt produced a robust increase in blood pressure from d 7 in ovariectomised females (n=5–9, P<0.05), similar to that observed in males. T and B cells in kidneys of male and female C57Bl6 mice were found to express GPER. In male RAG1‐deficient mice, aldosterone/salt had virtually no effect on blood pressure (n=8, P<0.05). However, adoptive transfer of 7×10 6 T cells from male C57Bl6 into male RAG1‐deficient mice fully restored the pressor response to aldosterone/salt, which could be attenuated by co‐treatment with G‐1 (n=8–14, P<0.05). This study indicates that activation of GPER by G‐1 and/or endogenous estrogen profoundly attenuates aldosterone/salt‐induced hypertension in mice. T cells are key contributors to aldosterone/salt‐induced hypertension, and therapeutic activation of GPER on T cells may reduce hypertension caused by elevated levels of aldosterone. Support or Funding Information NHMRC grant This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .