Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells.
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 endothelium-denuded rabbit aorta was associated with an increase in intracellular cyclic GMP level. This increase was abolished by the stereoselective inhibitor of nitric oxide-synthase, NG-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 Ca2(+)-calmodulin. The results indicate that cytokines induce a nitric oxide-synthase of the macrophage-type in vascular smooth muscle.
Busse
R
R
Department of Applied Physiology, University of Freiburg, FRG.
Mülsch
A
A
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D001013:Aorta, Thoracic; D001120:Arginine / Q000378:metabolism; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D001708:Biopterins; D009569:Nitric Oxide; D009249:NADP; D007371:Interferon-gamma; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C003402:sapropterin; D006152:Cyclic GMP