OBJECTIVETo investigate the expression and pathobiological implications of angiotensin II type 1 receptor (AT1R) in development of myocardial fibrosis of rats.

METHODSRat myocardial necrosis model was established using isoproterenol injection (15 mg/kg). Rat serum aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzymes (CK-MB) were detected by MD-100 automatic biochemical analyzer. Masson staining was used to evaluate the morphological changes. The expression of AT1R protein was determined by immunohistochemistry and its mRNA expression was analyzed by RT-PCR. The expression of collage type I and III was determined by immunohistochemistry.

RESULTSSerum LDH, CK and CK-MB reached their peaks at 4 h (chi2 = 16.90, P < 0.05), and AST achieved its peak in 6 h (chi2 = 16.90, P < 0.05). AT1R mRNA expression was increased 2 - 12 h after isoproterenol injection, but no statistical significance (P > 0.05) was observed comparing with the control. However, a significant AT1R mRNA increase was present at 24 h and decreased gradually after 48 h, and back to the control level after 3 weeks. Protein expression of AT1R increased proportionally with the severity of the fibrosis.

CONCLUSIONSAT1R mRNA and protein expressions increase significantly during myocardial ischemia, and is closely correlated with the fibrosis. These findings indicate that AT1R may play an important role in the pathogenesis of myocardial fibrosis.