The Research Of Prolylcarboxypeptidase Participate The Protection Effect Of Losartan On The Kidney Of Renovascular Hypertensive Rats

Object: The unbalance between renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) plays an important role in kidney pathological process of hypertension. Angiotenase C (prolylcarboxypeptidase, PRCP) is one of the regulators in maintaining the balance between RAS and KKS. In the present study, we investigated expression of PRCP in the two-kidney, one-clip (2K1C) hypertensive rats, and whether PRCP cascade involves the protection of losartan on the right kidney.Methods: Sparague-Dawley rats were used to develop the two-kidney, one-clip hypertensive rats, blood pressure (BP) was measured by tail-cuff method. The rats, systolic blood pressure≥140 mmHg, were adopted as hypertensive rats. All rats were randomly assigned to 6 groups. The hypertensive rats were treated with prazosin (5mg/kg/day) or losartan (5, 15, 45 mg/kg/day) or vehicle, respectively. After treated four weeks, the ratio of right kidney weight and body weight was calculated, and kidneys were sheared and preserved in 10% formalin for morphological analysis; K+,Na+,Creatinine and Blood Urea Nitrogen (BUN) of the serum were detected. The glomerular fibrosis degree was observed under the optical microscope. The expressions of PRCP mRNA in the kidneys were determined by RT-PCR. The contents of PRCP, tissue kallikrein, plasma kallikrein, TGF-β1 proteins in kidney or plasma were measured by western bloting.Results: The ratio of body weight and kidney weight,glomerular fibrosis degree of the hypertensive rats are significantly increased compared with sham rats. Meanwhile, PRCP, plasma kallikrein and tissue kallikrein expressions were significantly decreased in the untreated hypertensive rats. However, TGF-β1 expression significantly increased. Treatment of losartan decreased expression of TGF-β1 and increase expression of PRCP, plasma kallikrein and tissue kallikrein. The level of Na+,Creatinine and BUN in the serum decreased in a dose-dependent, but the serum K+ significantly increased after treated with losartan.Conclusion: The protective effects of losartan on the kidney of hypertensive rats are not only related to hypotension but also activation of the PRCP, there by increasing the expression of plasma kallikrein and tissue kallikrein and reducing the expression of TGF-β1.