J Korean Soc Emerg Med.
2017 Apr;28(2):201-207. 10.0000/jksem.2017.28.2.201.
Cardiac Physiologic Regulation of Sub-type Specific Adrenergic Receptors in Transgenic Mice Overexpressing β1- and β2-Adrenergic Receptors
- Affiliations
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- 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. cjhemd@kangwon.ac.kr
- 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. mhwon@kangwon.ac.kr
- KMID: 2379829
- DOI: http://doi.org/10.0000/jksem.2017.28.2.201
Abstract
- PURPOSE
A combination of β1-adrenergic receptor (βâ‚-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.
METHODS
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 βâ‚- and β₂-ARs (βâ‚- and β₂-AR TG mice, respectively).
RESULTS
Cardiac physiologic consequences of βâ‚- 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. βâ‚-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 βâ‚- and β₂-AR TG mice.
CONCLUSION
Hemodynamic evaluation performed in the present study showed a difference between βâ‚- and β₂-AR signaling, which may be due to a difference in the desensitization of βâ‚- and β₂-ARs.
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