title: Attenuation of salt-induced cardiac remodeling and diastolic dysfunction by the GPER agonist G-1 in female mRen2.Lewis rats.
abstract: BACKGROUND
  The G protein-coupled estrogen receptor (GPER) is expressed in various tissues including the heart. Since the mRen2.Lewis strain exhibits salt-dependent hypertension and early diastolic dysfunction, we assessed the effects of the GPER agonist (G-1, 40 nmol/kg/hr for 14 days) or vehicle (VEH, DMSO/EtOH) on cardiac function and structure.
  
  
  METHODS
  Intact female mRen2.Lewis rats were fed a normal salt (0.5% sodium; NS) diet or a high salt (4% sodium; HS) diet for 10 weeks beginning at 5 weeks of age.
  
  
  RESULTS
  Prolonged intake of HS in mRen2.Lewis females resulted in significantly increased blood pressure, mildly reduced systolic function, and left ventricular (LV) diastolic compliance (as signified by a reduced E deceleration time and E deceleration slope), increased relative wall thickness, myocyte size, and mid-myocardial interstitial and perivascular fibrosis. G-1 administration attenuated wall thickness and myocyte hypertrophy, with nominal effects on blood pressure, LV systolic function, LV compliance and cardiac fibrosis in the HS group. G-1 treatment significantly increased LV lusitropy [early mitral annular descent (e')] independent of prevailing salt, and improved the e'/a' ratio in HS versus NS rats (P<0.05) as determined by tissue Doppler.
  
  
  CONCLUSIONS
  Activation of GPER improved myocardial relaxation in the hypertensive female mRen2.Lewis rat and reduced cardiac myocyte hypertrophy and wall thickness in those rats fed a high salt diet. Moreover, these advantageous effects of the GPER agonist on ventricular lusitropy and remodeling do not appear to be associated with overt changes in blood pressure.
authors.affiliation: The Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina, United States of America.
authors.forename: Jewell A
authors.initials: JA
authors.lastname: Jessup
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Lindsey
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Mark C
authors.initials: MC
authors.lastname: Chappell
authors.forename: Leanne
authors.initials: L
authors.lastname: Groban
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D003517:Cyclopentanes / Q000494:pharmacology*; D003971:Diastole; D004452:Echocardiography; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D055647:Rats, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage
chemical_list: C517943:1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone; D003517:Cyclopentanes; D011804:Quinolines; D043562:Receptors, G-Protein-Coupled; C473112:Ren2 protein, mouse; D017673:Sodium Chloride, Dietary; D012083:Renin