Non-Haemodynamic Protective Effect Of Nitric Oxide On Tubulointerstitial Fibrosis After Unilateral Ureteral Obstruction In Rats

Objective Nitric Oxide mediated endothelium-dependent vasodilation and thus is a crucial regulator of vascular function and homeostasis. Its effect on tubulointerstitial fibrosis and the unhaemodynamic mechanism is still unknow. In our study, we developed a rat model of tubulointerstitial fibrosis by unilateral ureteral obstruction (UUO), and gave L-Arginine through intragastric administation or L-NAME through intraperitoneal injection. Then we examined the morphology and the expressions of FN and Arginaseâ…¡of the obstructive kidneys to investigate the effect of nitric oxide on renal interstitial fibrosis after unilateral obstruction and the unhaemodynamic mechanism.Methods Twenty-Four male Sprague-Dawley rats were randomly divided into four groupscontrol group(C): rats were treated with sham operation; model group(M): rats underwent UUO; L-Arginine group(A): rats underwent UUO and treated with L-Arginine; L-NAME group(N): rats underwent UUO and treated with L-NAME. Rats were sacrificed at day 28 after UUO operation,and the renal tissues were examined by HE, PAS, Masson and PASM stain. Immunohistochemistry and reverse transcription polymerase chain reation were applied to determine the protion of fibronectin and mRNA of Arginaseâ…¡. Results(1)Compared to group S, tubular atrophy, tubular cast, interstitial edema, tubulointerstitial fibrosis and inflammation was found in group M(P <0. 01); Com pared to group M, the lesion was attenuated in group A (P <0. 01) and was aggravated in group N (P <0. 01).(2)Compared to group M, The contents of nitric oxide in renal tissue increased in group A(P<0. 05), the contents decreased in group N(P<0. 01). (3)Compared to group S, The expression of fibronectin increased in group M(P <0. 01); Compared to group M, the expression decreased in group A(P <0. 05), which increased in group N(P <0. 01) . (4)Compared to group S, The expression of Arginaseâ…¡mRNA increased in group M(P <0. 01); Compared to group M, the expression decreased in group A(P <0. 05), which increased in group N(P <0. 01).Conclusions Nitric oxide may prevent the development of interstitial fibrosis through inhibiting extracellular matrix proliferation, Nitric oxide downregulating the expression of Arginaseâ…¡mRNA may be the mechanism.