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

Abstract

Altered sensitivity to the chronotropic and inotropic effects of catecholamines and reduction in β1/β2-adrenoceptor (β1/β2–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 β1-AR with or without up-regulation of β2-AR. AimsTo investigate the stress-induced behavior of β1-AR in the heart of mice expressing a non-functional β2-AR subtype. The guiding hypothesis is that the absence of β2-AR signaling will not affect the behavior of β1-AR during stress and that those are independent processes. Materials and methodsThe chronotropic and inotropic responses to β-AR agonists in isolated atria of stressed mice expressing a non-functional β2-AR were analyzed. The mRNA and protein expressions of β1- and β2–AR were also determined. Key findingsNo 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 β2- and β1-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 β1-AR was reduced at protein levels. SignificanceCollectively, our data provide evidence that the cardiac β2-AR is not essential for survival in a stressful situation and that the stress-induced reduction of β1-AR expression was independent of the β2-AR presence.