Role of NO and PAF in the impairment of skeletal muscle contractility induced by TNF-α

被引:36
作者
Alloatti, G
Penna, C
Mariano, F
Camussi, G
机构
[1] Univ Turin, Dipartimento Biol Anim & Uomo, Lab Fisiol Gen, I-10123 Turin, Italy
[2] Univ Turin, Ist Nazl Fis Mat, I-10123 Turin, Italy
[3] Univ Turin, Dipartimento Med Interna, I-10123 Turin, Italy
关键词
extensor digitorum longus; nitric oxide; platelet-activating factor; tumor necrosis factor-alpha;
D O I
10.1152/ajpregu.2000.279.6.R2156
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:R2156 / R2163
页数:8
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