Effects of nitric oxide on renal interstitial fibrosis in rats with unilateral ureteral obstruction.

It is well recognized that microvascular injury is a major determinant of renal fibrosis. Mounting evidence shows that nitric oxide (NO) plays an important role in angiogenesis. Therefore, we investigated to the effects of NO on kidney angiogenesis and renal fibrosis. In the present study, a unilateral ureteral obstruction (UUO) model was established with L-arginine (L-Arg, 1 g/dl) and N-nitro-L-arginine methyl ester (L-NAME, 5 mg/dl) serving as interference factors. We investigated the alteration of NO concentration with spectrophotometry, peritubular capillary (PTC) density with aminopeptidase P (JG12) immunohistochemical staining, and the expression of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), hypoxia inducible factor-1α (HIF-1α) and transforming growth factor-β1 (TGF-β1) with immunohistochemical staining and Western blotting at weeks 2, 3 and 4. Our findings showed that the expressions of VEGF, eNOS and PTC density were significantly decreased in rats with UUO, which was accompanied by a progressive increase in HIF-1α, TGF-β1 and an area of renal interstitial fibrosis. The administration of L-Arg promoted the synthesis of NO and significantly elevated the expressions of VEGF, eNOS and PTC density with the conspicuous loss of HIF-1α and TGF-β1 expressions and ultimately ameliorated renal fibrosis, which was markedly aggravated by L-NAME administration. These findings demonstrate that NO appears to play an important role in kidney angiogenesis and in slowing the progression of renal interstitial fibrosis, which suggests that NO may serve as a novel therapeutic strategy for preventing renal fibrosis as well as fibrosis in other organs.

Sun D ，Wang Y ，Liu C ，Zhou X ，Li X ，Xiao A ... -  《-》

Transplantation of endothelial progenitor cells alleviates renal interstitial fibrosis in a mouse model of unilateral ureteral obstruction.

Ma YY ，Sun D ，Li J ，Yin ZC ... -  《-》

Dietary arginine supplementation attenuates renal damage after relief of unilateral ureteral obstruction in rats.

Ito K ，Chen J ，Seshan SV ，Khodadadian JJ ，Gallagher R ，El Chaar M ，Vaughan ED Jr ，Poppas DP ，Felsen D ... -  《KIDNEY INTERNATIONAL》

Nitric oxide mediates ultrasound-induced hypoxia-inducible factor-1alpha activation and vascular endothelial growth factor-A expression in human osteoblasts.

Wang FS ，Kuo YR ，Wang CJ ，Yang KD ，Chang PR ，Huang YT ，Huang HC ，Sun YC ，Yang YJ ，Chen YJ ... -  《-》

Angiogenesis induced by endothelial nitric oxide synthase gene through vascular endothelial growth factor expression in a rat hindlimb ischemia model.

Namba T ，Koike H ，Murakami K ，Aoki M ，Makino H ，Hashiya N ，Ogihara T ，Kaneda Y ，Kohno M ，Morishita R ... -  《-》