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Role of Sex and GPER in Renal Damage Induced by Ang II Hypertension
Author(s) -
Aguerre Ines M.,
Gentry Kaylee M.,
Lindsey Sarah H.
Publication year - 2019
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.2019.33.1_supplement.569.3
Subject(s) - gper , endocrinology , medicine , estrogen receptor , kidney , masson's trichrome stain , h&e stain , renal medulla , estrogen , fibrosis , immunohistochemistry , cancer , breast cancer
The protective cardiovascular effects of estrogen are mediated by both the classic steroid receptors (ERα/β) and the novel G protein‐coupled estrogen receptor (GPER). We previously showed that genetic deletion of GPER does not alter the pressor response to Ang II but exacerbates pulse pressure and resistance artery contractility. The objective of the current study was to assess whether G protein‐coupled estrogen receptor (GPER) deletion is associated with evidence of renal damage in mice with intact ERα/β signaling. Male (M) and female (F) wildtype (wt) and GPER knockout (ko) mice were infused with Ang II (700 ng/kg/min) for two weeks. Kidneys were weighed, formalin‐fixed, and paraffin‐embedded. Renal damage was assessed in 4 mm sections mounted onto slides. Renal vascular fibrosis was quantified as percent of pixels with positive Masson's Trichrome staining, and renal infiltration was scored on a scale of 1–5 in sections stained with hematoxylin & eosin. Statistical analysis was completed using two‐way ANOVA. Kidney weights in Ang II‐infused mice were significantly higher in males (P< 0.0001) but were not impacted by GPER deletion (P=0.16; Fwt: 6.3 ± 0.2, Fko 6.1 ± 0.1, Mwt 7.6 ± 0.3, Mko 7.2 ± 0.2 mg/g body weight, n=7–9/group). Renal vascular fibrosis was not significantly affected by sex (P=0.29) or genotype (P=0.93). Interstitial infiltration was observed in the medulla, but there was no effect of sex (P=0.24) or genotype (P=0.58). Our findings indicate that neither sex nor GPER deletion significantly impacted renal damage in response to two week Ang II infusion. Future studies will determine whether sex and GPER play a role in renal damage when Ang II hypertension is induced for longer than two weeks. Support or Funding Information Funding was provided by NIH HL133619 to SHL. The STRIDE Fellowship is supported by the American Physiological Society and NIH HL115473. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .