An investigation into the expression and mechanism of action of urotensin II in chronic pressure-overloaded rat hearts

The present study aimed to investigate the role and mode of action of urotensin II (U II) in the occurrence and progression of cardiac fibrosis in a pressure-overload rat model. Coarctation of the abdominal aorta was used to establish an animal model, and postoperative echocardiography, hemodynamic detection, hematoxylin and eosin staining, Masson staining and immunohistochemistry were performed to assess the changes in cardiac function and pathology. The expression levels of U II, G-protein-coupled receptor 14 and collagen (Col) I and Col III in the myocardial tissues were also analyzed. Neonatal rat fibroblasts were isolated, cultured and subsequently, generations 3–5 were randomly divided into different groups for the detection of Col I and Col III levels by enzyme-linked immunosorbent assay and western blotting. The protein expression levels were markedly increased in the model group, and this increase correlated with an increase in myocardial fibrosis. In cultured neonatal rat fibroblast cells, 10(−8) mol/l U II significantly stimulated the synthesis of Col I and Col III (P<0.01) compared with the control group. Compared with the U II group, the administration of KT5720 (1 mol/l) or SB-611812 (1 mol/l) significantly reduced the synthesis and expression levels of Col I and Col III (P<0.05). U II may exert an important role in the process of myocardial fibrosis in chronic pressure-overload rats, and the cyclic adenosine monophosphate-protein kinase A signaling pathway may be partly involved in this process.