Glucose-induced down-regulation of NO production and inducible NOS expression in cultured rat aortic vascular smooth muscle cells: Role of protein kinase C

We studied the modulation of the inducible nitric oxide synthase (iNOS) in cultured rat smooth muscle cells using high concentrations of glucose. A dose-dependent decrease in the nitric oxide production induced by IL-1 beta was observed when cell cultures were pretreated with high glucose. Tn addition, the downregulation of nitric oxide production was also time- and dose-dependent. The decrease of nitric oxide production paralleled the decrease in the expression of iNOS. Protein kinase C inhibitor ameliorated the down-regulation of cytokine-induced nitric oxide production by high concentrations of glucose. Hyperosmolar concentrations of mannose had no effect on nitric oxide production. These findings suggest that high glucose in combination with stimulation by IL-1 beta decreases iNOS expression and nitric oxide production, and protein kinase C activation may be playing a role in the inhibition of nitric oxide production by high glucose. (C) 1996 Academic Press.