Cardiac Physiologic Regulation of Sub-type Specific Adrenergic Receptors in Transgenic Mice Overexpressing β1- and β2-Adrenergic Receptors.
- Author:
Ka Eul KIM
1
;
Hyun Jin TAE
;
Petrashevskaya NATALIA
;
Jae Chul LEE
;
Ji Hyeon AHN
;
Joon Ha PARK
;
In Hye KIM
;
Taek Geun OHK
;
Chan Woo PARK
;
Jun Hwi CHO
;
Moo Ho WON
Author Information
1. Department of Emergency Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
- Publication Type:Original Article
- Keywords:
Adrenergic receptors;
Transgenic mice;
Isoproterenol;
Inotropic;
Chronotropic
- MeSH:
Animals;
Depression;
Extremities;
Heart;
Heart Failure;
Hemodynamics;
Humans;
Infant;
Isoproterenol;
Mice;
Mice, Transgenic*;
Receptors, Adrenergic*
- From:Journal of the Korean Society of Emergency Medicine
2017;28(2):201-207
- CountryRepublic of Korea
- Language:Korean
-
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. 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 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.
