Cardiac physiologic regulation of sub-type specific adrenergic receptors in transgenic mice overexpressing β(1)- and β(2)-adrenergic receptors

OBJECTIVE: Combination of β(1)-adrenergic receptor (AR) blockade and β(2)-AR activation might be a potential novel therapy for treating heart failure. However, use of β-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 β-AR agonist (isoproterenol) in hearts isolated from 6-month-old transgenic (TG) mice overexpressing β(1)- and β(2)-ARs (β(1)- and β(2)-AR TG mice, respectively). RESULTS: Cardiac physiologic consequences of β(1)- and β(2)-AR overexpression resulted in similar maximal response to isoproterenol and faster temporary decline of positive inotropic response in β(2)-AR TG mice. β(1)-AR TG mice showed a pronounced negative limb of FFR, whereas β(2)-AR TG mice showed high stimulation frequencies with low contractile depression during FFR. In contrast, Frank-Starling relationship was equally enhanced in both β(1)- and β(2)-AR TG mice. CONCLUSION: Hemodynamic evaluation performed in the present showed a difference in β(1)- and β(2)-AR signaling, which may be due to the difference in the desensitization of β(1)- and β(2)-ARs.