Role of 5‐HT2B receptors in cardiomyocyte apoptosis in noradrenaline‐induced cardiomyopathy in rats |
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Authors: | Chong‐Feng Bai Jin‐Cheng Liu Rong Zhao Wei Cao Shui‐Bin Liu Xiao‐Nan Zhang Hong‐Ju Guo Qi Yang Ding‐Hua Yi Ming‐Gao Zhao |
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Affiliation: | 1. Department of Cardiac Surgery, Xijing Hospital;2. Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an, China |
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Abstract: | 1. Serotonin (5‐hydroxytryptamine; 5‐HT) plays important roles in the development of cardiac hypertrophy via activation of 5‐HT receptors. The aim of the present study was to investigate the role of 5‐HT2B receptors in the development of cardiomyocyte apoptosis and hypertrophy associated with noradrenaline (NA) overload. 2. Cardiac hypertrophy was induced in rats by intraperitoneal injection of 1.5 mg/kg NA for 4 weeks. Starting from Day 15, 5‐HT2B receptor antagonist SB 204741 (i.p., 0.5 or 2 mg/kg) or SDZ SER 082 (i.p., 1 mg/kg) was injected twice daily for another 14 days. Whole‐cell patch‐clamp techniques were used to record ionic currents in freshly isolated ventricular cardiomyocytes. Western blot and terminal deoxyribonucleotidyl transferase‐mediated dUTP–digoxigenin nick end‐labelling (TUNEL) assays were used to assess myocardial apoptosis. 3. Expression of 5‐HT2B receptors was enhanced in the hypertrophic left ventricle induced by NE overload in vivo. The 5‐HT2B receptor antagonist SB 204741 partially reversed cardiac hypertrophy induced by NE overload (P < 0.05) and decreased L‐type calcium currents in ventricular cardiomyocytes (P < 0.05). In addition, SB 204741 notably attenuated myocardial apoptosis, as evidenced by downregulation of Bax and caspase 3 (P < 0.05) and upregulation of the anti‐apoptotic Bcl‐2 protein (P < 0.05). 4. In conclusion, the data suggest an involvement of 5‐HT2B receptors in the generation of apoptotic events associated with cardiac remodelling during increased adrenergic stimulation. |
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Keywords: | apoptosis cardiac hypertrophy myocardium noradrenaline serotonin |
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