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
μg/kg), iv], followed by sc (1.5 μg/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, 5×10-9–5×10-7 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.
Keywords:
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
μg/kg), iv], followed by sc (1.5 μg/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, 5×10-9–5×10-7 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.