Adaptation to exercise-induced stress is not dependent on cardiomyocyte α1A-adrenergic receptors

Kaidonis, Xenia and Niu, Wenxing and Chan, Andrea Y. and Kesteven, Scott and Wu, Jianxin and Iismaa, Siiri E. and Vatner, Stephen and Feneley, Michael and Graham, Robert M. (2021) Adaptation to exercise-induced stress is not dependent on cardiomyocyte α1A-adrenergic receptors. Journal of Molecular and Cellular Cardiology, 155. pp.78-87. ISSN 00222828

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Link to published document: http://doi.org/10.1016/j.yjmcc.2021.02.010

Abstract

The 'fight or flight' response to physiological stress involves sympathetic nervous system activation, catecholamine release and adrenergic receptor stimulation. In the heart, this induces positive inotropy, previously attributed to the beta1-adrenergic receptor subtype. However, the role of the alpha1A-adrenergic receptor, which has been suggested to be protective in cardiac pathology, has not been investigated in the setting of physiological stress. To explore this, we developed a tamoxifen-inducible, cardiomyocyte-specific alpha1A-adrenergic receptor knock-down mouse model, challenged mice to four weeks of endurance swim training and assessed cardiac outcomes. With 4-OH tamoxifen treatment, expression of the alpha1A-adrenergic receptor was knocked down by 80-89%, without any compensatory changes in the expression of other adrenergic receptors, or changes to baseline cardiac structure and function. Swim training caused eccentric hypertrophy, regardless of genotype, demonstrated by an increase in heart weight/tibia length ratio (30% and 22% in vehicle- and tamoxifen-treated animals, respectively) and an increase in left ventricular end diastolic volume (30% and 24% in vehicle- and tamoxifen-treated animals, respectively) without any change in the wall thickness/chamber radius ratio. Consistent with physiological hypertrophy, there was no increase in fetal gene program (Myh7, Nppa, Nppb or Acta1) expression. In response to exercise-induced volume overload, stroke volume (39% and 30% in vehicle- and tamoxifen-treated animals, respectively), cardiac output/tibia length ratio (41% in vehicle-treated animals) and stroke work (61% and 33% in vehicle- and tamoxifen-treated animals, respectively) increased, regardless of genotype. These findings demonstrate that cardiomyocyte alpha1A-adrenergic receptors are not necessary for cardiac adaptation to endurance exercise stress and their acute ablation is not deleterious.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 31 Jul 2021 05:10
Last Modified: 31 Jul 2021 05:10
URI: http://eprints.victorchang.edu.au/id/eprint/1087

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