Regulation of the nitric oxide synthase-nitric oxide-cGMP pathway in rat mesenteric endothelial cells

Most of the available data on the nitric oxide (NO) pathway in the vasculat ure is derived from studies performed with cells isolated from conduit arte ries. We investigated the expression and regulation of components of the NO synthase (NOS)-NO-cGMP pathway in endothelial cells from the mesenteric va scular bed. Basally, or in response to bradykinin, cultured mesenteric endo thelial cells (MEC) do not release NO and do not express endothelial NOS pr otein. MEC treated with cytokines, but not untreated cells, express inducib le NOS (iNOS) mRNA and protein, increase nitrite release, and stimulate cGM P accumulation in reporter smooth muscle cells. Pretreatment of MEC with ge nistein abolished the cytokine-induced iNOS expression. On the other hand, exposure of MEC to the microtubule depolymerizing agent colchicine did not affect the cytokine-induced increase in nitrite formation and iNOS protein expression, whereas it inhibited the induction of iNOS in smooth muscle cel ls. Collectively, our findings demonstrate that MEC do not express endothel ial NOS but respond to inflammatory stimuli by expressing iNOS, a process t hat is blocked by tyrosine kinase inhibition but not by microtubule depolym erization.