The Role of Cyclooxygenase Enzymes in the Effects of Losartan and Lisinopril on the Contractions of Rat Thoracic Aorta.
OBJECTIVE To investigate the effect of high glucose and losartan on cell proliferation and cyclooxygenase-2 (COX2) expression in normal human mesangial cells (NHMCs), and to examine the effect of losartan on COX2 and transforming growth factor-beta1 (TGF-beta1) expression in a model of diabetic nephropathy (DN). METHODS NHMCs were cultured in vitro in high glucose media with or without losartan. NHMCs proliferation and COX2 expression were determined by WST-1, Western blot, and RT-PCR. The rat model of DN was produced by injections of streptozocin (STZ). After the treatment with losartan for 4 weeks, glomerular hypertrophy, urinary thromboxane B2 (TXB2) and 24 h urinary protein counts were measured, and COX2 and TGF-beta1 expressions were investigated using immunohistochemical techniques and RT-PCR. RESULTS Losartan dose-dependently inhibited the proliferation of NHMCs in response to high glucose. Losartan also decreased COX2 expression in NHMCs at high or low glucose concentrations. In vivo experiments found kidney weight/body weight (KW/BW), urinary TXB2 and 24 h urinary protein counts increased significantly in the DN group. Losartan reduced KW/BW, urinary TXB2, and 24 h urinary protein counts and significantly suppressed the over-expression of COX2 and TGF-beta1. CONCLUSION Losartan reduces COX2 expression in NHMCs,especially at high glucose concentrations. Losartan could suppress the expression of COX2 and TGF-beta1 in the kidney of DN rats and attenuate the renal lesions caused by DN.