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

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

Clinical and Experimental Emergency Medicine, September 2016

27752636

Ka Eul Kim, Hyun-Jin Tae, Petrashevskaya Natalia, Jae-Chul Lee, Ji Hyeon Ahn, Joon Ha Park, In Hye Kim, Taek Geun Ohk, Chan Woo Park, Jun Hwi Cho, Moo-Ho Won

Combination of β1-adrenergic receptor (AR) blockade and β2-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. 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 β1- and β2-ARs (β1- and β2-AR TG mice, respectively). Cardiac physiologic consequences of β1- and β2-AR overexpression resulted in similar maximal response to isoproterenol and faster temporary decline of positive inotropic response in β2-AR TG mice. β1-AR TG mice showed a pronounced negative limb of FFR, whereas β2-AR TG mice showed high stimulation frequencies with low contractile depression during FFR. In contrast, Frank-Starling relationship was equally enhanced in both β1- and β2-AR TG mice. Hemodynamic evaluation performed in the present showed a difference in β1- and β2-AR signaling, which may be due to the difference in the desensitization of β1- and β2-ARs.