Differential β-adrenoceptor expression induced by nerve growth factor infusion into the canine right and left stellate ganglia |
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Authors: | Shengmei Zhou MD Offir Paz MD Ji-Min Cao MD Kamlesh Asotra PhD Ning-Ning Chai MD PhD Charles Wang MD PhD Lan S. Chen MD Michael C. Fishbein MD Behrooz Sharifi MD Peng-Sheng Chen MD |
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Affiliation: | aDivision of Cardiology, Department of Medicine bDivision of Endocrinology and the General Clinical Research Center, Cedars-Sinai Medical Center cDepartment of Neurology, Children’s Hospital and the Keck School of Medicine, University of Southern California dDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California |
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Abstract: | BACKGROUND: Nerve growth factor (NGF) infusion into the right stellate ganglion (RSG) is antiarrhythmic, while NGF infusion into the left stellate ganglion (LSG) is proarrhythmic in dogs with myocardial infarction (MI) and complete atrioventricular block (CAVB). This functional asymmetry suggests differential neural remodeling. OBJECTIVES: To test the hypothesis that NGF infusion into the RSG and the LSG can lead to differential beta-adrenoceptor (beta-AR) expression in dogs with MI and CAVB. METHODS AND RESULTS: We performed immunostaining to quantify beta(1)-AR and beta(3)-AR immunoreactivity in six dogs with MI and CAVB, nine dogs with MI, CAVB, and NGF infusion to the LSG, six dogs with MI, CAVB, and NGF infusion to the RSG, and six normal dogs. There was significantly increased beta(3)-AR immunoreactivity in dogs with NGF infusion into the LSG and significantly decreased beta(3)-AR immunoreactivity in dogs with NGF infusion into the RSG compared with controls and with the MI and CAVB group. There were no significant differences in beta(1)-AR immunoreactivity among these four groups. To determine protein and mRNA expression of beta-ARs, we created MI and CAVB and infused NGF into the LSG in six additional dogs. The noninfarcted left ventricle free wall was harvested 1 week later. The protein level and receptor density of beta(3)-AR (but not beta(1)- or beta(2)-AR) significantly increased in these six dogs compared with normal controls. CONCLUSIONS: We conclude that NGF infusion into the RSG and the LSG in dogs with MI and CAVB induced differential beta(3)-AR expression in the left ventricular myocardium. |
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Keywords: | Receptors, adrenergic, beta Death, sudden Nervous system, sympathetic Arrhythmia |
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