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

Authors: Zhang, YG  Li, YG  Liu, BG  Wei, RH  Wang, DM  Tan, XR  Bu, DF  Pang, YZ  Tang, CS 
Citation: Zhang YG, etal., Acta Pharmacol Sin. 2007 Jan;28(1):36-43.
Pubmed: (View Article at PubMed) PMID:17184580
DOI: Full-text: DOI:10.1111/j.1745-7254.2007.00485.x

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 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). CONCLUSION: These results suggest that UII was involved in the development of cardiac fibrosis and hypertrophy by synergistic effects with ISO.

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RGD Object Information
RGD ID: 2306814
Created: 2009-05-07
Species: All species
Last Modified: 2009-05-07
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.