BACKGROUND/AIM: Increased nitric oxide (NO) generation and action have been suggested to be associated with glomerular hyperfiltration and increased vascular permeability early in @entity6 . However, previous studies have primarily focused on the constitutive nitric oxide synthase (cNOS) pathway present in endothelial cells, and the role of the inducible NOS ( @entity1506 ) pathway in @entity2316 has remained unclear. This study examined whether high glucose modulates NO synthesis by the @entity1506 pathway in @entity35 mesangial cells. In addition, the effect of inhibition of the @entity1506 pathway on fibronectin production was determined to examine the role of the @entity1506 pathway in high glucose-induced extracellular expansion by mesangial cells. METHODS: NO synthesis by the @entity1506 pathway was evaluated by nitrite and @entity1506 mRNA and protein productions. The effects of @entity7131 ( @entity7131 ) inhibitor and aldose reductase inhibitor on the @entity1506 mRNA expression and aminoguanidine, a relatively specific inhibitor of the @entity1506 on fibronectin protein production were examined. RESULTS: High 30 mM glucose concentration led to significant increases in nitrite production of @entity35 mesangial cells upon stimulation with lipopolysaccharide (LPS) plus @entity3692 ( @entity3692 ) compared with control 5.6 mM glucose concentration. Mesangial @entity1506 mRNA expression and protein production also increased significantly in response to high glucose. The addition of calphostin C, a @entity7131 inhibitor, and 6-bromo-1,3-dioxo-1H-benz[d,e]isoquinoline-2(3H)-acetic acid, an aldose reductase inhibitor, significantly suppressed the enhancement of @entity1506 mRNA expression in high glucose concentration. High glucose also significantly increased fibronectin protein production of mesangial cells upon stimulation with LPS plus @entity3692 compared to control glucose. Aminoguanidine reversed this high glucose-induced fibronectin production at dose inhibiting @entity1506 mRNA expression. CONCLUSIONS: These results indicate that high glucose enhances cytokine-induced NO production by @entity35 mesangial cells, and that the activation of @entity7131 and aldose reductase pathway may play a role in this enhancement. In addition, high glucose-induced NO production by the @entity1506 pathway may promote extracellular matrix accumulation by mesangial cells under certain condition.

High glucose increases inducible NO production in cultured XXXX mesangial cells. Possible role in fibronectin production.

@entity3692 :: ('25712(Tax:10116)', 'Gene') :: ['IFN-gamma', 'interferon-gamma'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes'] @entity1506 :: ('24599(Tax:10116)', 'Gene') :: ['iNOS'] @entity2316 :: ('MESH:D003928', 'Disease') :: ['diabetic nephropathy'] @entity7131 :: ('MESH:D020151', 'Disease') :: ['protein kinase C', 'PKC'] @entity35 :: ('10116', 'Species') :: ['rat']
@entity35 :: (10116,Species) :: ['rat']
