Busse R, Mülsch A
Department of Applied Physiology, University of Freiburg, FRG.
FEBS Lett. 1990 Nov 26;275(1-2):87-90. doi: 10.1016/0014-5793(90)81445-t.
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.
我们研究了细胞因子导致血管平滑肌对血管收缩剂反应性降低的机制。在内皮剥脱的兔主动脉中，细胞因子、肿瘤坏死因子和白细胞介素-1孵育6至24小时后，去甲肾上腺素诱导的收缩减弱，这与细胞内环鸟苷酸水平升高有关。一氧化氮合酶的立体选择性抑制剂NG-硝基-L-精氨酸和环己酰亚胺可消除这种升高。通过激活纯化的可溶性鸟苷酸环化酶，在细胞因子处理的天然和培养的平滑肌细胞的胞质溶胶中检测到一氧化氮的形成，其依赖于四氢生物蝶呤，而不依赖于Ca2(+)-钙调蛋白。结果表明，细胞因子在血管平滑肌中诱导巨噬细胞型一氧化氮合酶。
