Role of NO and PAF in the impairment of skeletal muscle contractility induced by TNF-α
Role of NO and PAF in the impairment of skeletal muscle contractility induced by TNF-α
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DOI：
10.1152/ajpregu.2000.279.6.r2156
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发表时间：
2000-12-01
影响因子：
2.8
通讯作者：
Camussi, G
中科院分区：
文献类型：
--
作者：
Alloatti, G;Penna, C;Camussi, G
研究了血小板活化因子(PAF)和一氧化氮(NO)在肿瘤坏死因子-α(TNF-α)对豚鼠伸趾长肌(EDL)骨骼肌收缩力影响中的作用。肿瘤坏死因子-α(5-10 ng/ml)可降低各刺激频率(1-200 Hz)的收缩能力，并使力频关系右移。N-G-硝基-L-精氨酸甲酯(L-NAME，1 mM)的保护作用，而不是N-G-硝基-D-精氨酸甲酯(D-NAME，1 mM)的保护作用，以及PAF受体拮抗剂WEB-2170的抑制作用，表明了NO和PAF作为肿瘤坏死因子-α的介导物的作用。肿瘤坏死因子-α增加PAF和NO的产生。与肿瘤坏死因子-α类似，非生成性化合物S-亚硝基-N-乙酰青霉胺(0.5-1 mM)和PAF(10-20 nM)均降低内分泌细胞的收缩能力。L-NAME而不是D-NAME阻断了PAF的负面作用。阻断PAF合成所需的磷脂酶A(2)可显著降低肿瘤坏死因子-α的作用。WEB-2170抑制肿瘤坏死因子-α诱导的NO合成和PAF刺激的NO合成。这些结果表明，PAF和NO均参与了肿瘤坏死因子-α诱导的机械改变的发生，并且NO的产生是PAF合成的下游环节。
The role of platelet-activating factor (PAF) and nitric oxide (NO) as mediators of the effects of tumor necrosis factor-alpha (TNF-alpha) on skeletal muscle contractility was studied in guinea pig extensor digitorum longus (EDL) muscle. TNF-alpha (5-10 ng/ml) reduced contractility at every stimulation frequency (1-200 Hz) and shifted the force-frequency relationship to the right. The role of NO and PAF as mediators of TNF-alpha was suggested by the protective effect of N-G-nitro-L-arginine methyl ester (L-NAME; 1 mM), but not of N-G-nitro-D-arginine methyl ester (D-NAME; 1 mM), and by the inhibitory effect of the PAF-receptor antagonist WEB-2170 (3 muM). TNF-alpha increased the production of PAF and NO. Similar to TNF-alpha, both S-nitroso-N-acetylpenicillamine (0.5-1 mM), an NO-generating compound, and PAF (10-20 nM) reduced EDL contractility. L-NAME, but not D-NAME, blocked the negative effect of PAF. Blockade of phospholipase A(2), which is required for PAF synthesis, significantly reduced the effects of TNF-alpha. WEB-2170 inhibited NO synthesis induced by TNF-alpha and PAF-stimulated NO production. These results suggest that both PAF and NO contribute to the development of the mechanical alterations induced by TNF-alpha and that NO production is downstream to the synthesis of PAF.