Urotensin II accelerates cardiac fibrosis and hypertrophy of rats induced by isoproterenol.
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.
Zhang
Yong-Gang
YG
Department of Cardiovascular Diseases, First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China. zhangyg8686@hotmail.com
Li
Yu-Guang
YG
Liu
Bao-Guo
BG
Wei
Rui-Hong
RH
Wang
Dong-Ming
DM
Tan
Xue-Rui
XR
Bu
Ding-Fang
DF
Pang
Yong-Zheng
YZ
Tang
Chao-Shu
CS
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*
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