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

Acta Pharmacologica Sinica 2007年第1期28卷 36-43页

作者： Yong-gang ZHANG~(2,5) Yu-guang LI~2 Bao-guo LIU~3 Rui-hong WEI~2 Dong-ming WANG~2 Xue-rui TAN~2 Ding-fang BU~4 Yong-zheng PANG~4 Chao-shu TANG~42 Department of Cardiovascular Diseases,First Affiliated Hospital,Shantou University Medical College,Shantou 515041,China 3 The Affiliated Hospital,Medical School of Hebei University of Engineering,Hebei 056029,China,4 Institute of Cardiovascular Research,Peking University First Hospital,Beijing 100034,China Department of Cardiovascular Diseases First Affiliated Hospital Shantou University Medical College Shantou China The Affiliated Hospital Medical School of Hebei University of Engineering Hebei China Institute of Cardiovascular Research Peking University First Hospital Beijing China

Aim:To study whether urotensin II（UII）,a potent vasoconstrictive peptide,isinvolved in the development of cardiac hypertrophy and fibrogenesis of ratsinduced by isoproterenol（ISO）.Methods:Thirty male Wistar rats were randomlydivided into 3 *** 1 was the healthy control group,group 2 was the ISOgroup,and group 3 was the ISO+UII *** groups 2 and 3,ISO(5 mg-kg-1.d-1)wasgiven（sc）once daily for 7 *** 3 was also given UII in the first day [3 nmol/kg（5μg/kg）,iv],followed by sc（1.5 μg/kg）twice *** 1 received 0.9% *** receptor（UT）mRNA expression was determined by *** contents ofUII and angiotensin II（Ang II）were determined by *** vitro,the effects of UII on DNA/collagen synthesis of cardiac fibroblasts were deter-mined by [3H]thymidine/[3H]proline ***:The ratio of heartweight/body weight,plasma lactate dehydrogenase activity,myocardialmalondialdehyde and hydroxyproline concentration increased significantly in theISO group,as well as UT mRNA expression,plasma and cardiac UII and ventricu-lar Ang II,compared with the control group（P<0.01）.ISO induced significantmyocardial ***,UII+ISO co-treatment significantly increasedthe changes of biochemical markers of injury and the degree of cardiac hypertro-phy and *** vitro,5×10～9-5×10-7mol/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 ofcardiac fibrosis and hypertrophy by synergistic effects with ISO.

关键词： cardiac remodeling cardiac fibrosis gpr14 receptor urotensin II collagen

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