Open AccessUrotensin II accelerates cardiac fibrosis and hypertrophy of rats induced by isoproterenol 1
Author(s) -
ZHANG Yonggang,
LI Yuguang,
LIU Baoguo,
WEI Ruihong,
WANG Dongming,
TAN Xuerui,
BU Dingfang,
PANG Yongzheng,
TANG Chaoshu
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00485.x
Subject(s) - urotensin ii , medicine , endocrinology , hydroxyproline , malondialdehyde , myocardial fibrosis , fibrosis , radioimmunoassay , cardiac fibrosis , chemistry , muscle hypertrophy , saline , angiotensin ii , receptor , oxidative stress
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 [ 3 H]thymidine/[ 3 H]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 [ 3 H]thymidine/[ 3 H] 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.