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GPR30 activation in salt‐sensitive mRen2.Lewis females induces beneficial effects independent of alterations in blood pressure
Author(s) -
Lindsey Sarah Hoffmann,
Chappell Mark C.
Publication year - 2009
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.23.1_supplement.1017.18
Subject(s) - endocrinology , medicine , blood pressure , vasoconstriction , chemistry , estrogen receptor , gper , agonist , receptor , cancer , breast cancer
Female mRen2.Lewis (mRen2) rats display only mild increases in blood pressure in comparison to male littermates unless ovariectomized or fed a high salt (HS) diet. This estrogen‐ and salt‐sensitive model may reflect the higher pressure and salt‐sensitivity associated with the postmenopausal state. We reported that in vivo activation of the novel estrogen receptor GPR30 by the agonist G‐1 significantly reduced blood pressure and Ang II‐induced vasoconstriction in ovariectomized mRen2. The current study assessed whether GPR30 activation ameliorates salt‐sensitive hypertension and vascular dysfunction in intact mRen2 fed a HS diet (4% Na+, 10 wks). Systolic pressures in HS females treated with G‐1 were not different from HS controls (G‐1: 225±4 vs. 238±9 mmHg; n=5 each). G‐1 significantly reduced Ang II vasoconstriction in both endothelium‐intact (10% vs. 16%; P <0.01) and denuded aortic rings (19% vs. 26%; P <0.05). In addition, G‐1 reduced renal hypertrophy (4.4±0.1 vs. 5.0±0.1 mg/g body weight; P <0.01) and cardiac hypertrophy (4.8±0.1 vs. 5.4±0.1 mg/g; P <0.01). G‐1 also enhanced creatinine clearance (1.94±0.3 vs. 0.97±0.2 ml/min; P <0.05) and reduced proteinuria (98±33 vs. 331±67 mg/mg creatinine; P <0.05). We conclude that activation of the estrogen receptor GPR30 induces beneficial cardiovascular actions in the salt‐sensitive mRen2 strain independent from changes in blood pressure.