ABSTRACT
To investigate the effect of losartan on the axis of prolylcarboxypeptidase (PRCP)--kallikrein of the two-kidney, one-clipped (2K1C) hypertensives rats, and explore the novel protection mechanism of losartan on the kidney. Sprague-Dawley (SD) rats were used to develop the 2K1C hypertensive rats. Then, the rats were treated with prazosin (5 mg x kg(-1) x d(-1)) or losartan (5, 15 and 45 mg x kg(-1) x d(-1)) or vehicle, separately. At the same time, the blood pressures were observed. After treated for four weeks, the ratio of right kidney weight and body weight, the change of glomerular morphology, and K+, Na+, creatinine and blood urea nitrogen (BUN) of the serum were used for evaluation of kidney. The expressions of PRCP mRNA in the kidneys were determined by RT-PCR. The protein levels of PRCP, tissue kallikrein, plasma kallikrein, TGF-beta1 in kidney or plasma were measured by Western blotting. Results showed that the changes of body weight and kidney weight ratio, glomerular fibrosis degree and the biochemistrical index of serum induced by hypertension were relieved when the hypertensive rats treated with losartan for four weeks. Meanwhile, treatment of losartan also significantly decreased expression of TGF-beta1 and increased expressions of PRCP, plasma kallikrein and tissue kallikrein. The protective effects of losartan on the kidney of 2K1C hypertensive rats are activation of the axis of PRCP-kallikrein and reducing the expression of TGF-beta1.