Enhanced Myocardial Relaxation In Vivo in Transgenic Mice Overexpressing the β2-Adrenergic Receptor

We have previously shown that the inotropic state of the intact mouse can be significantly increased with overexpression of the β2-adrenergic receptor (β2-ADR). However whether processes involving myocardial relaxation would also be influenced are unknown. Accordingly, transgenic mice that were created with cardiac-specific overexpression of the β2-ADR ( 200 fold increase in β-ADR density and 2 fold increase in basal adenylyl cyclase activity) were studied using 2F high fidelity micromanometer placed in the left ventricle (LV) of anesthetized intact transgenic (TG) (n = 7) and control (C) (n = 7) mice. Hemodynamic parameters measured were LV pressure, minimum first derivative of the LV pressure (LV dP/dtmin) and the time constant of isovolumic LV pressure decay (Tau) at baseline and after progressive doses of isoproterenol (ISO).In conclusion, overexpression of β2-ADR resulted in significant reduction in LV dP/dtmin associated with shortening of Tau which was largely unaffected by ISO infusion. This suggests markedly enhanced myocardial relaxation in vivo which is most likely due to increased Ca2+ uptake into the sarcoplasmic reticulum.