Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells

Abstract

We investigated the mechanisms by which cytokines lead to a diminished responsiveness of vascular smooth muscle to vasoconstrictors. The attenuation of noradrenaline‐induced contraction by 6 to 24 h incubations with the cytokines, tumor necrosis factor and interleukin‐1, in endotheliumdenuded rabbi, aorta was associated with an increase in intracellular cyclic GMP level. This increase was abolished by the stereoselective inhibitor of nitric oxide‐synthase. N ^o‐nitro‐L‐arginine and by cycloheximide. Formation of nitric oxide was detected in the cytosol of cytokine‐treated native and cultured smooth muscle cells by activation of purified soluble guanylate cyclase, and depended on tetrahydrobiopterin, but not on ? ‐calmodulin. The results indicate that cytokines induce a nitric oxide‐synthase of the macrophage‐type in vascular smooth muscle.