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Cardiovascular Pharmacology

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

Abstract

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 first day [3 nmol/kg (5 ug/kg), iv], followed by sc (1.5 ug/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, 5×10−9-5×10−7mol/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 of cardiac fibrosis and hypertrophy by synergistic effects with ISO.

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Correspondence to Yong-gang Zhang.

Additional information

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

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Zhang, Yg., Li, Yg., Liu, Bg. et al. Urotensin II accelerates cardiac fibrosis and hypertrophy of rats induced by isoproterenol. Acta Pharmacol Sin 28, 36–43 (2007). https://doi.org/10.1111/j.1745-7254.2007.00485.x

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Keywords

  • cardiac remodeling
  • cardiac fibrosis
  • GPR14 receptor
  • urotensin II
  • collagen

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