CYTOKINE-INDUCED EXPRESSION OF A NITRIC-OXIDE SYNTHASE IN RAT RENAL TUBULE CELLS

Nitric oxide (NO.) has been implicated in the regulation of renal vasc ular tone and tubular sodium transport. While the endothelial cell is a well known source of NO., recent studies suggest that tubular epithe lial cells may constitutively generate NO.. An inducible isoform of ni tric oxide synthase which produces far greater quantities of NO. exist s in some cell types. We sought to determine whether kidney epithelial cells exposed to cytokines could express an inducible nitric oxide sy nthase. Primary cultures of rat proximal tubule and inner medullary co llecting duct cells generated NO. on exposure to TNF-alpha and IFN-gam ma. NO. production by both cell types was inhibited by N(G)-monomethyl -L-arginine; this inhibition was partially reversed by the addition of excess L-arginine. Stimulation of kidney epithelial cells with TNF-al pha and IFN-gamma dramatically increased the level of inducible nitric oxide synthase mRNA. In summary, renal proximal tubule and inner medu llary collecting duct cells can produce NO. via expression of an induc ible isoform of nitric oxide synthase.