The Effect of Rennin-angiotensin System on Endothelin-1 and Nitric Oxide in Rat Glomerulosclerosis

Objective To investigate the correlation among glomerulosclerosis and endothelin-1(ET-1) and nitric oxide(NO), and the effect of blocking renin-angiotensin system(RAS) on rat glomerulosclerosis. Methods 30 SD rats underwent unilateral nephrectomy plus adriamycin (6mg/kg) injection through caudal vein to establish rat glomerulosclerosis models. These rats were divided randomly into glomerulosclerosis group (group D), Benazepril treatment group (group DB) and Losartan treatment group (group DL). Another 10 SD rats served as sham-operation group (group C). 6 weeks after treamtent, the mRNA and protein expressions of ET-1 and iNOS in renal cortex were detected using RT-PCR and Western blotting analysis respectively, and the content of fibronectin(Fn) was measured using immunohistochemical method. Results Group D occurred massive proteinuria, hypoalbuminemia and hypercholesterolemia, which had significant differences compared with group C (P0 05). Compared with group C, the expression level of ET-1mRNA and protein in the renal cortex of group D increased 2 58 and 1 83 times respectively, the expression level of iNOS mRNA and protein increased 3 28 and 2 15 times respectively, and there was a significant increase in the content of Fn as well. 6 weeks after treatment, there was significant improvement in the blood and urine biochemical indices and renal pathological lesions in groups DB and DL, the mRNA and protein expressions of ET-1 and iNOS were down-regulated, and the expression of Fn protein also decreased(P0 05). Conclusion ET-1 and NO played important roles in the early stage of rat glomerulosclerosis. Blocking RAS using Benazepril or Losartan could decrease the glomerular extracellular matrix deposit.