Regulation of contractility and metabolic signaling by the β2-adrenergic receptor in rat ventricular muscle

Abstract

AimsCardiac function is modulated by the sympathetic nervous system through β-adrenergic receptor (β-AR) activity and this represents the main regulatory mechanism for cardiac performance. To date, however, the metabolic and molecular responses to β2-agonists are not well characterized. Therefore, we studied the inotropic effect and signaling response to selective β2-AR activation by tulobuterol. Main methodsStrips of rat right ventricle were electrically stimulated (1Hz) in standard Tyrode solution (95% O2, 5% CO2) in the presence of the β1-antagonist CGP-20712A (1μM). A cumulative dose–response curve for tulobuterol (0.1–10μM), in the presence or absence of the phosphodiesterase (PDE) inhibitor IBMX (30μM), or 10min incubation (1μM) with the β2-agonist tulobuterol was performed. Key findingsβ2-AR stimulation induced a positive inotropic effect (maximal effect=33±3.3%) and a decrease in the time required for half relaxation (from 45±0.6 to 31±1.8ms, −30%, p<0.001) after the inhibition of PDEs. After 10min of β2-AR stimulation, p-AMPKαT172 (54%), p-PKBT308 (38%), p-AS160T642 (46%) and p-CREBS133 (63%) increased, without any change in p-PKAT197. SignificanceThese results suggest that the regulation of ventricular contractility is not the primary function of the β2-AR. Rather, β2-AR could function to activate PKB and AMPK signaling, thereby modulating muscle mass and energetic metabolism of rat ventricular muscle.