title: Urotensin II accelerates cardiac fibrosis and hypertrophy of rats induced by isoproterenol.
abstract: OBJECTIVE
  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 x kg(-1) x d(-1)) was given (sc) once daily for 7 d. Group 3 was also given UII in the first day [3 nmol/kg (5 microg/kg), iv], followed by sc (1.5 microg/kg) twice daily. Group 1 received 0.9% saline. UII receptor (UT) mRNA expression was determined by RT-PCR. The contents of UII 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/[3H]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 x 10(-9 )-5 x 10(-7 ) mol/L UII stimulated [3H]thymidine/[3H] proline incorporation into cardiac fibroblasts in a dose-dependent manner (P< 0.01).
  
  
  CONCLUSIONS
  These results suggest that UII was involved in the development of cardiac fibrosis and hypertrophy by synergistic effects with ISO.
authors.affiliation: Department of Cardiovascular Diseases, First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China. zhangyg8686@hotmail.com
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Zhang
authors.forename: Yu-Guang
authors.initials: YG
authors.lastname: Li
authors.forename: Bao-Guo
authors.initials: BG
authors.lastname: Liu
authors.forename: Rui-Hong
authors.initials: RH
authors.lastname: Wei
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Wang
authors.forename: Xue-Rui
authors.initials: XR
authors.lastname: Tan
authors.forename: Ding-Fang
authors.initials: DF
authors.lastname: Bu
authors.forename: Yong-Zheng
authors.initials: YZ
authors.lastname: Pang
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D006332:Cardiomegaly / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D006909:Hydroxyproline / Q000378:metabolism; D007545:Isoproterenol; D045022:Lactate Dehydrogenases / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014579:Urotensins / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C473142:Uts2r protein, rat; D000804:Angiotensin II; D008315:Malondialdehyde; D003094:Collagen; C029677:urotensin II; D045022:Lactate Dehydrogenases; D007545:Isoproterenol; D006909:Hydroxyproline