中国病理生理杂志2011，Vol.27Issue(10)：1873-1878,6.DOI:10.3969/j.issn.1000-4718.2011.10.004
NCA增加心肌收缩力的作用研究
1-Nitrosocyclohexyl acetate increases contractile force of cardiac muscle
摘要
Abstract
AIM: To investigate the effect of 1 - nitrosocyclohexyl acetate ( NCA, a newly - developed nitroxyl donor ) on myofibrils of rat heart. METHODS: Trabecular muscles were dissected from the right ventricles of the rat hearts and mounted between a force transducer and a motor arm. The muscles were supervised with K - H solution ( pH 7. 4 ) at room temperature. Fura - 2 was loaded into the trabecular muscles via electrophoresis. The length of the sarcomere was set to 2. 2 - 2. 3 μm. During steady - state activations, the maximal Ca2+ - activated force ( Fmax ) and Ca2+ required for 50% activation ( Ca50 ) were measured. The change of tropomyosin was detected by Western blotting. RESULTS: Twitch force increased in a dose - dependent manner in the presence of NCA at the concentrations from 20 μmol/L to 100 μmol/L. The force increased ( P < 0. 01 ) and [ Ca 2+ ]1 transient remained unchanged ( P > 0. 05 ) with various frequencies ( 0. 5 - 3. 0 Hz ), 20 μmol/L of NCA and 0. 5 mmol/L of Ca2+ . Both diastolic force and [ Ca2+]1 were not affected by NCA. Compared with the control data, NCA at concentration of 20 μmol/L increased Fmax[ ( 124. 0 ± 15. 0 ) mN/mm2 vs ( 90. 0 ± 4. 2 ) mN/mm2 , P < 0. 05 ] and decreased Ca50 ( 0. 39 ± 0. 01 ) μmol/L vs ( 0. 57 ± 0. 03 ) μmol/L, P < 0. 01 ] during steady - state activations. The Hill coefficient was not affected ( 3. 94 ± 0. 18 vs 4. 92 ± 0. 84, P > 0. 05 ). The skinned force increased ( P <0. 05 ). Under non - reducing condition, a cross - linking band in tropomyosin was observed by Western blotting. The thiol reducing agent dithiothreitol both prevented and reversed NCA action, confirming NCA/nitroxyl red-ox sensitivity. CONCLUSION: NCA, a donor of pure nitroxyl, represents a new class of agents that are capable of direct-ly sensitizing cardiac myofibrils to Ca 2+ . Post - translational thiol modification of key regulatory myofilament proteins ( I. E. Tropomyosin ) may underlie the effects of NCA.关键词
硝酰基/乙酸1-亚硝基环已酯/原肌球蛋白Key words
Nitroxyl/1 - Nitrosocyclohexyl acetate/Tropomyosin分类
医药卫生引用本文复制引用
钟鑫,贾洪丽,侯俊青,王育文,时飒,李志韬..NCA增加心肌收缩力的作用研究[J].中国病理生理杂志,2011,27(10):1873-1878,6.基金项目
黑龙江省教育厅科学技术研究资助项目(No.11551157) （No.11551157）
