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J Korean Soc Emerg Med > Volume 28(2); 2017 > Article
Journal of The Korean Society of Emergency Medicine 2017;28(2): 201-207.
Cardiac Physiologic Regulation of Sub-type Specific Adrenergic Receptors in Transgenic Mice Overexpressing β1- and β2-Adrenergic Receptors
Ka Eul Kim1, Hyun-Jin Tae2,3, Petrashevskaya Natalia4, Jae-Chul Lee5, Ji Hyeon Ahn5, Joon Ha Park5, In Hye Kim5, Taek Geun Ohk2, Chan Woo Park2, Jun Hwi Cho2, Moo-Ho Won5
1Department of Emergency Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
2Department of Biomedical Science, Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Korea
3Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Korea
4Cardiopulmonary Genomics Program, Departments of Medicine and Physiology, University of Maryland School of Medicine, Baltimore, USA
5Department of Neurobiology, Kangwon National University School of Medicine, Chuncheon, Korea
Correspondence  Jun Hwi Cho ,Tel: 033-258-2378, Fax: 033-258-2451, Email: cjhemd@kangwon.ac.kr,
Moo-Ho Won ,Tel: 033-250-8891, Fax: 033-256-1614, Email: mhwon@kangwon.ac.kr,
Received: March 13, 2017; Revised: March 15, 2017   Accepted: March 22, 2017.  Published online: April 30, 2017.
ABSTRACT
Purpose:
A combination of β1-adrenergic receptor (β1-AR) blockade and β2-AR activation might potentially be the novel therapy for treating heart failure. However, the use of β-AR agonists and/or antagonists in the clinical setting is controversial due to the lack of information on cardiac inotropic or chronotropic regulation by AR signaling.
Method:
In this study, we performed a hemodynamic evaluation by examining the force frequency response (FFR), Frank-Starling relationship, and response to non-selective β-AR agonist (isoproterenol) in the 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 a similar maximal response to that of 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. Contrastingly, Frank-Starling relationship was equally enhanced in both β1- and β2-AR TG mice.
Conclusion:
Hemodynamic evaluation performed in the present study showed a difference between β1- and β2-AR signaling, which may be due to a difference in the desensitization of β1- and β2-ARs.
Key words: Adrenergic receptors, Transgenic mice, Isoproterenol, Inotropic, Chronotropic
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