Effect of stress on the chronotropic and inotropic responses to β-adrenergic agonists in isolated atria of KOβ2 mice

Altered sensitivity to the chronotropic and inotropic effects of catecholamines and reduction in beta(1)/beta(2)-adrenoceptor (beta(1)/beta(2)-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 beta(1)-AR with or without up-regulation of beta(2)-AR. Aims: To investigate the stress-induced behavior of beta(1)-AR in the heart of mice expressing a non-functional beta(2)-AR subtype. The guiding hypothesis is that the absence of beta(2)-AR signaling will not affect the behavior of beta(1)-AR during stress and that those are independent processes. Materials and methods: The chronotropic and inotropic responses to beta-AR agonists in isolated atria of stressed mice expressing a non-functional beta(2)-AR were analyzed. The mRNA and protein expressions of beta(1)- and beta(2)-AR were also determined. Key findings: 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 beta(2)- and beta(1)-AR antagonists 50 nM ICI118,551 and 300 nM CGP20712A, respectively. Sensitivity and maximum response to the beta-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 beta(1)-AR was reduced at protein levels. Significance: Collectively, our data provide evidence that the cardiac beta(2)-AR is not essential for survival in a stressful situation and that the stress-induced reduction of beta(1)-AR expression was independent of the beta(2)-AR presence.

Automated summary

Altered sensitivity to catecholamines and reduction in beta(1)/beta(2)-adrenoceptor ratio were observed in failing and senescent human heart, as well as in stressed rats. This study aimed to investigate the role of beta(1)-adrenoceptor (beta(1)-AR) in stressed mice expressing a non-functional beta(2)-AR. The results showed that the absence of beta(2)-AR signaling did not affect the behavior of beta(1)-AR during stress, and the reduction of beta(1)-AR expression was independent of beta(2)-AR presence.