title: Signaling via GPR30 protects the myocardium from ischemia/reperfusion injury.
abstract: BACKGROUND
  Estrogen may protect against the development of cardiovascular disease. Recently, a receptor known as GPR30 that seems to mediate estrogen's nongenomic effects has been identified. We hypothesized that the activation of GPR30 protects cardiac function and decreases myocardial inflammation after global ischemia/reperfusion (I/R).
  
  
  METHODS
  Hearts from male Sprague-Dawley rats were perfused via Langendorff and treated with either (1) vehicle; (2) 10 nm of the GPR30 agonist, G-1; or (3) 100 nm of G-1; they then were subjected to 25 minutes of ischemia and 40 minutes of reperfusion. Cardiac functional parameters were measured continuously. Ventricular tissue was analyzed for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6.
  
  
  RESULTS
  At end-reperfusion, the left ventricular developed pressure in the 100-nm G-1 group was improved compared with vehicle (26% +/- 12% equilibrium vs 54% +/- 9% equilibrium; P < .05). Similar findings were noted when comparing the 100-nm G-1 group with the vehicle in terms of +dP/dt (53% +/- 12% equilibrium vs 26% +/- 19%, respectively; P < .05) and -dP/dt (56% +/- 15% equilibrium vs 22% +/- 16% equilibrium, respectively; P < .05). TNF-alpha, IL-1beta, and IL-6 levels were lower in myocardium of the 100-nm G-1 group compared with the vehicle (P < .05).
  
  
  CONCLUSIONS
  The GPR30 agonist, G-1, improves functional recovery and decreases myocardial inflammation after global I/R. GPR30 may play an important role in estrogen's ability to protect the heart against I/R injury.
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Brent R
authors.initials: BR
authors.lastname: Weil
authors.forename: Mariuxi C
authors.initials: MC
authors.lastname: Manukyan
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Herrmann
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Abarbanell
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Poynter
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Meldrum
mesh_terms: D000818:Animals; D003517:Cyclopentanes / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
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; D004967:Estrogens; C520305:Gper1 protein, rat; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D011804:Quinolines; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha