Literature citations

beta2-adrenoceptor transfection enhances contractile reserve of isolated rat ventricular myocytes exposed to chronic isoprenaline stimulation by improving beta1-adrenoceptor responsiveness.

ContextHeart 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 β-adrenergic signal system, suppressing β-adrenoceptors (β-ARs)-mediated contractile support in the failing heart.ObjectiveWe investigated the effects of β(2)-AR gene transfer on shortening amplitude of isolated ventricular myocytes under chronic exposure to isoprenaline (ISO), and further determine the contributions of β(1)-AR and β(2)-AR to the contraction.Materials and methodsCardiomyocytes were isolated from adult rat hearts and then transfected with β(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 β(2)-AR. Video-based edge-detection system was used to evaluate basal and ISO-stimulated shortening amplitudes of cardiomyocytes.Resultsβ(2)-AR gene transfer increased β(2)-AR protein content. Chronic ISO stimulation produced a negative inotropic response, whereas acute ISO stimulation showed a positive inotropic response. β(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 β(1)-AR antagonist, CGP 20712A, instead of β(2)-AR antagonist, ICI 118,551.Discussion and conclusionsWe conclude that β(2)-AR gene transfer in isolated ventricular myocytes under chronic ISO stimulation improves cellular contraction, and the beneficial effects might be mediated by improving β(1)-adrenoceptor responsiveness.

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