Effect of stress on the chronotropic and inotropic responses to β-adrenergic agonists in isolated atria of KOβ 2 mice

• Published in: Life sciences (1973) Vol. 322; p. 121644
• Main Authors: de Moura, Andre Luiz, Brum, Patricia Chakur, de Carvalho, Ana Elisa Teofilo Saturi, Spadari, Regina Celia
• Format: Journal Article
• Language: English
• Published: Netherlands 01-06-2023
• Subjects: Adrenergic beta-Agonists - pharmacology; Adrenergic beta-Antagonists - metabolism; Adrenergic beta-Antagonists - pharmacology; Albuterol - pharmacology; Animals; Dobutamine - metabolism; Dobutamine - pharmacology; Heart Atria - metabolism; Humans; Isoproterenol - metabolism; Isoproterenol - pharmacology; Mice; Rats; Receptors, Adrenergic, beta-1 - genetics; Receptors, Adrenergic, beta-1 - metabolism; Receptors, Adrenergic, beta-2 - metabolism; Stress response; β-Adrenoceptors knockout mice; Cardiac adrenoceptors
• ISSN: 1879-0631

Altered sensitivity to the chronotropic and inotropic effects of catecholamines and reduction in β
/β
-adrenoceptor (β
/β
-AR) ratio were reported in failing and in senescent human heart, as well as in isolated atria and ventricle of rats submitted to stress. This was due to downregulation of β
-AR with or without up-regulation of β
-AR.
To investigate the stress-induced behavior of β
-AR in the heart of mice expressing a non-functional β
-AR subtype. The guiding hypothesis is that the absence of β
-AR signaling will not affect the behavior of β
-AR during stress and that those are independent processes.
The chronotropic and inotropic responses to β-AR agonists in isolated atria of stressed mice expressing a non-functional β
-AR were analyzed. The mRNA and protein expressions of β
- and β
-AR were also determined.
No deaths were observed in mice under stress protocol. Atria of stressed mice displayed reduced sensitivity to isoprenaline compared to the controls, an effect that was abolished by the β
- and β
-AR antagonists 50 nM ICI118,551 and 300 nM CGP20712A, respectively. Sensitivity and maximum response to the β-agonists dobutamine and salbutamol were not altered by stress or ICI118,551. The responses to dobutamine and salbutamol were prevented by CGP20712A. The expression of β
-AR was reduced at protein levels.
Collectively, our data provide evidence that the cardiac β
-AR is not essential for survival in a stressful situation and that the stress-induced reduction of β
-AR expression was independent of the β
-AR presence.