β2-adrenoceptor transfection enhances contractile reserve of isolated rat ventricular myocytes exposed to chronic isoprenaline stimulation by improving β1-adrenoceptor responsiveness.
BACKGROUND
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 β-adrenergic signal system, suppressing β-adrenoceptors (β-ARs)-mediated contractile support in the failing heart.


OBJECTIVE
We 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.


METHODS
Cardiomyocytes 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.


RESULTS
β(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.


CONCLUSIONS
We 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.
Department of Physiology, Xuzhou Medical College, Xuzhou, China.
XinWei
X
Jiang
ChuanYing
C
Xu
Ying
Y
Wang
LiPing
L
Gao
ChangDong
C
Yan
DongYe
D
Li
Hong
H
Sun
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006333:Heart Failure / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D061251:Primary Cell Culture; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics*
D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; C026777:ICI 118551; C049763:CGP 20712A; D007545:Isoproterenol