Cardiac physiologic regulation of subtype specific adrenergic receptors in transgenic mice overexpressing beta(1)- and beta(2)-adrenergic receptors

Objective Combination of beta(1)-adrenergic receptor (AR) blockade and beta(2)-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 beta(1)- and beta(2)-ARs (beta(1)- and beta(2)-AR TG mice, respectively). Results Cardiac physiologic consequences of beta(1)- and beta(2)-AR overexpression resulted in similar maximal response to isoproterenol and faster temporary decline of positive inotropic response in beta(2)-AR TG mice. beta(1)-AR TG mice showed a pronounced negative limb of FFR, whereas beta(2)-AR TG mice showed high stimulation frequencies with low contractile depression during FFR. In contrast, Frank-Starling relationship was equally enhanced in both beta(1)- and beta(2)-AR TG mice. Conclusion Hemodynamic evaluation performed in the present showed a difference in beta(1)- and beta(2)-AR signaling, which may be due to the difference in the desensitization of beta(1)- and beta(2)-ARs.