Urotensin Ⅱ accelerates cardiac fibrosis and hypertrophy of rats induced by isoproterenol  

作　　者：Yong-gang ZHANG Yu-guang LI Bao-guo LIU Rui-hong WEI Dong-ming WANG Xue-rui TAN Ding-fang BU Yong-zheng PANG Chao-shu TANG 

机构地区：[1]Department of Cardiovascular Diseases, First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China [2]The Affiliated Hospital, Medical School of Hebei University of Engineering, Hebei 056029, China [3]Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China

出　　处：《Acta Pharmacologica Sinica》2007年第1期36-43,共8页中国药理学报（英文版）

基　　金：Project supported by the China Postdoctoral Science Foundation(No 2003033439);supported by the National Natural Science Foundation of China(No 30470730);the Medical Science Foundation of Hebei Province Health Department(No 2 K010).

摘　　要：Aim： To study whether urotensin Ⅱ （UⅡ）, a potent vasoconstrictive peptide, is involved in the development of cardiac hypertrophy and fibrogenesis of rats induced by isoproterenol （ISO）. Methods： Thirty male Wistar rats were randomly divided into 3 groups. Group 1 was the healthy control group, group 2 was the ISO group, and group 3 was the ISO＋UⅡ group. In groups 2 and 3, ISO （5 mg·kg^-1·d^-1） was given （sc） once daily for 7 d. Group 3 was also given UⅡ in the fwst day [3 nmol/kg （5 lag/kg）, iv], followed by sc （1.5 μg/g） twice daily. Group 1 received 0.9% saline. UⅡ receptor （UT） mRNA expression was determined by RT-PCR. The contents of Uμ and angiotensin Ⅱ （Ang Ⅱ） were determined by radioimmunoassay. In vitro, the effects of UⅡ on DNA/collagen synthesis of cardiac fibroblasts were determined by [^3H]thymidine/[63H]proline incorporation. Results： The ratio of heart weight/body weight, plasma lactate dehydrogenase activity, myocardial malondialdehyde and hydroxyproline concentration increased significantly in the ISO group, as well as UT mRNA expression, plasma and cardiac UII and ventricular Ang Ⅱ, compared with the control group （P〈0.01）. ISO induced significant myocardial fibrogenesis. Moreover, UⅡ＋ISO co-treatment significantly increased the changes of biochemical markers of injury and the degree of cardiac hypertrophy and fibrosis. In vitro, 5× 10^-9-5× 10^-7 mol/L UⅡ stimulated [3H]thymidine/[^3H] proline incorporation into cardiac fibroblasts in a dose-dependent manner （P〈0.01 ）. Conclusion： These results suggest that UⅡ was involved in the development of cardiac fibrosis and hypertrophy by synergistic effects with ISO.Aim： To study whether urotensin Ⅱ （UⅡ）, a potent vasoconstrictive peptide, is involved in the development of cardiac hypertrophy and fibrogenesis of rats induced by isoproterenol （ISO）. Methods： Thirty male Wistar rats were randomly divided into 3 groups. Group 1 was the healthy control group, group 2 was the ISO group, and group 3 was the ISO＋UⅡ group. In groups 2 and 3, ISO （5 mg·kg^-1·d^-1） was given （sc） once daily for 7 d. Group 3 was also given UⅡ in the fwst day [3 nmol/kg （5 lag/kg）, iv], followed by sc （1.5 μg/g） twice daily. Group 1 received 0.9% saline. UⅡ receptor （UT） mRNA expression was determined by RT-PCR. The contents of Uμ and angiotensin Ⅱ （Ang Ⅱ） were determined by radioimmunoassay. In vitro, the effects of UⅡ on DNA/collagen synthesis of cardiac fibroblasts were determined by [^3H]thymidine/[63H]proline incorporation. Results： The ratio of heart weight/body weight, plasma lactate dehydrogenase activity, myocardial malondialdehyde and hydroxyproline concentration increased significantly in the ISO group, as well as UT mRNA expression, plasma and cardiac UII and ventricular Ang Ⅱ, compared with the control group （P〈0.01）. ISO induced significant myocardial fibrogenesis. Moreover, UⅡ＋ISO co-treatment significantly increased the changes of biochemical markers of injury and the degree of cardiac hypertrophy and fibrosis. In vitro, 5× 10^-9-5× 10^-7 mol/L UⅡ stimulated [3H]thymidine/[^3H] proline incorporation into cardiac fibroblasts in a dose-dependent manner （P〈0.01 ）. Conclusion： These results suggest that UⅡ was involved in the development of cardiac fibrosis and hypertrophy by synergistic effects with ISO.

关 键 词：cardiac remodeling cardiac fibrosis GPR14receptor urotensin II COLLAGEN 

分 类 号：R543[医药卫生—心血管疾病]