beta2-adrenoceptor transfection enhances contractile reserve of isolated rat ventricular myocytes exposed to chronic isoprenaline stimulation by improving beta1-adrenoceptor responsiveness.
Authors:
Jiang, X Xu, C Wang, Y Gao, L Yan, C Li, D Sun, H
Citation:
Jiang X, etal., J Recept Signal Transduct Res. 2012 Feb;32(1):36-41.
CONTEXT: Heart failure (HF) is a progressive deterioration in heart function associated with overactivity of the sympathetic nervous system. Elevated sympathetic nervous system activity down regulates the beta-adrenergic signal system, suppressing beta-adrenoceptors (beta-ARs)-mediated contractile support in the failing heart. OBJECTIVE: We investigated the effects of beta(2)-AR gene transfer on shortening amplitude of isolated ventricular myocytes under chronic exposure to isoprenaline (ISO), and further determine the contributions of beta(1)-AR and beta(2)-AR to the contraction. MATERIALS AND METHODS: Cardiomyocytes were isolated from adult rat hearts and then transfected with beta(2)-AR gene using an adenovirus vector. Four hours after the infection, cardiomyocytes were treated with ISO for another 24 hours to imitate high levels of circulating catecholamines in HF. Western blotting was performed to measure myocardial protein expression of beta(2)-AR. Video-based edge-detection system was used to evaluate basal and ISO-stimulated shortening amplitudes of cardiomyocytes. RESULTS: beta(2)-AR gene transfer increased beta(2)-AR protein content. Chronic ISO stimulation produced a negative inotropic response, whereas acute ISO stimulation showed a positive inotropic response. beta(2)-AR gene transfer had no significant effects on shortening amplitude of cardiomyocytes under normal conditions, but enhanced the blunted contraction of cardiomyocytes under pathological conditions induced by chronic ISO stimulation, and the effect was inhibited by beta(1)-AR antagonist, CGP 20712A, instead of beta(2)-AR antagonist, ICI 118,551. DISCUSSION AND CONCLUSIONS: We conclude that beta(2)-AR gene transfer in isolated ventricular myocytes under chronic ISO stimulation improves cellular contraction, and the beneficial effects might be mediated by improving beta(1)-adrenoceptor responsiveness.