Cardiac physiologic regulation of sub-type specific adrenergic receptors in transgenic mice overexpressing β1- and β2-adrenergic receptors

Abstract

OBJECTIVE: Combination of beta1-adrenergic receptor (AR) blockade and beta2-AR activation might be a potential novel therapy for treating heart failure. However, use of beta-AR agonists and/or antagonists in the clinical setting is controversial because of the lack of information on cardiac inotropic or chronotropic regulation by AR signaling. METHODS: In this study, we performed hemodynamic evaluation by examining force frequency response (FFR), Frank-Starling relationship, and response to a non-selective beta-AR agonist (isoproterenol) in hearts isolated from 6-month-old transgenic (TG) mice overexpressing beta1- and beta2-ARs (beta1- and beta2-AR TG mice, respectively). RESULTS: Cardiac physiologic consequences of beta1- and beta2-AR overexpression resulted in similar maximal response to isoproterenol and faster temporary decline of positive inotropic response in beta2-AR TG mice. beta1-AR TG mice showed a pronounced negative limb of FFR, whereas beta2-AR TG mice showed high stimulation frequencies with low contractile depression during FFR. In contrast, Frank-Starling relationship was equally enhanced in both beta1- and beta2-AR TG mice. CONCLUSION: Hemodynamic evaluation performed in the present showed a difference in beta1- and beta2-AR signaling, which may be due to the difference in the desensitization of beta1- and beta2-ARs.