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KMID : 0385920170280020201
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Journal of the Korean Society of Emergency Medicine
2017 Volume.28 No. 2 p.201 ~ p.207
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Cardiac Physiologic Regulation of Sub-type Specific Adrenergic Receptors in Transgenic Mice Overexpressing β1- and β2-Adrenergic Receptors
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Kim Ka-Eul
Tae Hyun-Jin
Natalia Petrashevskaya
Lee Jae-Chul
Ahn Ji-Hyeon
Park Joon-Ha
Kim In-Hye
Ohk Taek-Geun
Park Chan-Woo
Cho Jun-Hwi
Won Moo-Ho
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Abstract
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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.
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KEYWORD
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Adrenergic receptors, Transgenic mice, Isoproterenol, Inotropic, Chronotropic
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