title: Cardiac physiologic regulation of sub-type specific adrenergic receptors in transgenic mice overexpressing β1- and β2-adrenergic receptors.
abstract: OBJECTIVE
  Combination of β1-adrenergic receptor (AR) blockade and β2-AR activation might be a potential novel therapy for treating heart failure. However, use of β-AR agonists and/or antagonists in the clinical setting is controversial because of the lack of information on cardiac inotropic or chronotropic regulation by AR signaling.
  
  
  METHODS
  In this study, we performed hemodynamic evaluation by examining force frequency response (FFR), Frank-Starling relationship, and response to a non-selective β-AR agonist (isoproterenol) in hearts isolated from 6-month-old transgenic (TG) mice overexpressing β1- and β2-ARs (β1- and β2-AR TG mice, respectively).
  
  
  RESULTS
  Cardiac physiologic consequences of β1- and β2-AR overexpression resulted in similar maximal response to isoproterenol and faster temporary decline of positive inotropic response in β2-AR TG mice. β1-AR TG mice showed a pronounced negative limb of FFR, whereas β2-AR TG mice showed high stimulation frequencies with low contractile depression during FFR. In contrast, Frank-Starling relationship was equally enhanced in both β1- and β2-AR TG mice.
  
  
  CONCLUSIONS
  Hemodynamic evaluation performed in the present showed a difference in β1- and β2-AR signaling, which may be due to the difference in the desensitization of β1- and β2-ARs.
authors.affiliation: Department of Biomedical Science, Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Korea.
authors.forename: Ka Eul
authors.initials: KE
authors.lastname: Kim
authors.affiliation: Department of Emergency Medicine, Kangwon National University School of Medicine, Chuncheon, Korea; Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Tae
authors.affiliation: CardioPulmonary Genomics Program, Departments of Medicine and Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Petrashevskaya
authors.initials: P
authors.lastname: Natalia
authors.affiliation: Department of Neurobiology, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Neurobiology, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Neurobiology, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Joon Ha
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Neurobiology, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Emergency Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Taek Geun
authors.initials: TG
authors.lastname: Ohk
authors.affiliation: Department of Emergency Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Chan Woo
authors.initials: CW
authors.lastname: Park
authors.affiliation: Department of Emergency Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Jun Hwi
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Neurobiology, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
keywords: Adrenergic receptors; Chronotropic; Inotropic; Isoproterenol; Transgenic mice