Dispersion of ventricular mRNA of RyR2 and SERCA2 associated with arrhythmogenesis in rats  

作　　者：Hong-lanWANG De-zaiDAI FengGAO Yan-pinZHANG FengLU 

机构地区：[1]ResearchDivisionofPharmacology,ChinaPharmaceuticalUniversity,Nanjing210009,China [2]LaboratorialCenterofMedicine,SoutheastUniversity,Nanjing210009,China

出　　处：《Acta Pharmacologica Sinica》2004年第6期738-743,共6页中国药理学报（英文版）

基　　金：Supported by Key Project from the National Natural ScienceFoundation of China; No 30230170.

摘　　要：AIM: To investigate the effect of CPU86017 on the changes of mRNA abundance of different calcium handling system in infarcted heart. METHODS: Rats were subjected to left coronary ligation to induce myocardial infarc- tion (MI). The treatment with either propranolol (Pro) 5 mg/kg ip or CPU86017 1, 2, and 4 mg/kg ip was initiated on the next day of operation and continued for 20 d. Medication with isoproterenol (Isop) 3 mg/kg sc started on the d 17-21. Ventricular mRNA abundance of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca2+-ATPase (SERCA2), L-type Ca2+ channel, and Na+/Ca2+exchanger (NCX1) were measured. RESULTS: Arrhythmic scores (AS) in the Isop group was raised up to 5.27±1.75 (P<0.01) vs myocardial infarction group 2.25±2.04 and sham group 1.50±1.73. The AS was depressed by Pro (1.63±1.53, P<0.01 vs Isop), and CPU86017 2 and 4 mg/kg (3.00±1.24, and 1.70±1.85, P<0.01 vs Isop). The significant dispersion of depressed mRNA abundance of RyR2 and SERCA2 was associated with an increase in AS in Isop group, and it was much depressed in the left than the right ventricle. The dispersion and depression of mRNA were restored significantly by Pro and CPU86017, asso- ciated with suppression on AS. In Isop group, the mRNA abundance of L-type Ca2+ channel was not changed; and a moderate increase in the mRNA of NCX1 was seen, the changes were regressed by Pro and CPU86017. CONCLUSION: Isop-induced arrhythmogenesis in MI heart was correlated mainly with a dispersion of depressed mRNA abundance in ventricle likely due to the consequence of PKA over-phosphorylation. A suppression of arrhythmia by Pro and CPU86017 resulted from a regression of the dispersion and depression of RyR2 and SERCA2.AIM: To investigate the effect of CPU86017 on the changes of mRNA abundance of different calcium handling system in infarcted heart. METHODS: Rats were subjected to left coronary ligation to induce myocardial infarc- tion (MI). The treatment with either propranolol (Pro) 5 mg/kg ip or CPU86017 1, 2, and 4 mg/kg ip was initiated on the next day of operation and continued for 20 d. Medication with isoproterenol (Isop) 3 mg/kg sc started on the d 17-21. Ventricular mRNA abundance of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca2+-ATPase (SERCA2), L-type Ca2+ channel, and Na+/Ca2+exchanger (NCX1) were measured. RESULTS: Arrhythmic scores (AS) in the Isop group was raised up to 5.27±1.75 (P<0.01) vs myocardial infarction group 2.25±2.04 and sham group 1.50±1.73. The AS was depressed by Pro (1.63±1.53, P<0.01 vs Isop), and CPU86017 2 and 4 mg/kg (3.00±1.24, and 1.70±1.85, P<0.01 vs Isop). The significant dispersion of depressed mRNA abundance of RyR2 and SERCA2 was associated with an increase in AS in Isop group, and it was much depressed in the left than the right ventricle. The dispersion and depression of mRNA were restored significantly by Pro and CPU86017, asso- ciated with suppression on AS. In Isop group, the mRNA abundance of L-type Ca2+ channel was not changed; and a moderate increase in the mRNA of NCX1 was seen, the changes were regressed by Pro and CPU86017. CONCLUSION: Isop-induced arrhythmogenesis in MI heart was correlated mainly with a dispersion of depressed mRNA abundance in ventricle likely due to the consequence of PKA over-phosphorylation. A suppression of arrhythmia by Pro and CPU86017 resulted from a regression of the dispersion and depression of RyR2 and SERCA2.

关 键 词：myocardial infarction ISOPROTERENOL ARRHYTHMIA CALCIUM 4-chlorobenzyltetrahydroberberine 

分 类 号：R542.22[医药卫生—心血管疾病]