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

AIMS

Cardiac 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 β(2)-agonists are not well characterized. Therefore, we studied the inotropic effect and signaling response to selective β(2)-AR activation by tulobuterol.

MAIN METHODS

Strips of rat right ventricle were electrically stimulated (1Hz) in standard Tyrode solution (95% O(2), 5% CO(2)) in the presence of the β(1)-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 β(2)-agonist tulobuterol was performed.

KEY FINDINGS

β(2)-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 β(2)-AR stimulation, p-AMPKα(T172) (54%), p-PKB(T308) (38%), p-AS160(T642) (46%) and p-CREB(S133) (63%) increased, without any change in p-PKA(T197).

SIGNIFICANCE

These results suggest that the regulation of ventricular contractility is not the primary function of the β(2)-AR. Rather, β(2)-AR could function to activate PKB and AMPK signaling, thereby modulating muscle mass and energetic metabolism of rat ventricular muscle.