Maréchal G, Beckers-Bleukx G
Department of Physiology, School of Medicine, UCL 5540, Av. Hippocrate 55, B-1200, Brussels, Belgium.
Pflugers Arch. 1998 Nov;436(6):906-13. doi: 10.1007/s004240050722.
Maximum velocity of shortening, Vo, was measured by the method of Edman [J Physiol (Lond) 291:143-159, 1979] on extensor digitorum longus muscles of a mouse in vitro at 20 degreesC. Blockers of nitric oxide synthase, 10 mM nitro-l-arginine or 1 mM 7-nitroindazole, reduced Vo by 18% and 22%, respectively. On removal of the inhibitor, Vo returned to the control value. It was found that 10 mM nitro-d-arginine, an enantiomer of nitro-l-arginine inactive against nitric oxide synthase, did not affect Vo. A donor of nitric oxide, 0.1 mM nitroprusside, increased Vo by 15%. It removed the inhibition caused by nitro-l-arginine. Another donor of nitric oxide, 1 microM (+/-)-S-nitroso-N-acetylpenicillamine (SNAP), increased Vo by 8%. An inhibitor of cGMP synthase, 0.01 mM Ly-83583, decreased Vo by 18%. An analogue of cGMP, 0.1 mM 8-bromo-cGMP, increased Vo by 17%. A general inhibitor of phosphodiesterases, 0.02 mM 3-isobutyl-1-methylxanthine (IBMX), increased Vo by 17%. An inhibitor specific of cGMP phosphodiesterase, 0.01 mM dipyridamole, increased Vo by 8%. The maximal isometric force (F0) was not modified by the drugs, except by 7-nitroindazole and Ly-83583, which depressed F0 by 12%. The cGMP level in tetanized muscles decreased by 12-27% in the presence of blockers of nitric oxide synthase. We conclude that the level of intracellular nitric oxide modulates Vo through the cGMP pathway.
在20℃下，采用埃德曼法[《生理学杂志》（伦敦）291:143 - 159，1979]对体外培养的小鼠趾长伸肌测量最大缩短速度（Vo）。一氧化氮合酶抑制剂10 mM硝基-L-精氨酸或1 mM 7-硝基吲唑分别使Vo降低了18%和22%。去除抑制剂后，Vo恢复到对照值。发现10 mM硝基-D-精氨酸，即对一氧化氮合酶无活性的硝基-L-精氨酸的对映体，不影响Vo。一氧化氮供体0.1 mM硝普钠使Vo增加了15%。它消除了硝基-L-精氨酸引起的抑制作用。另一种一氧化氮供体1 μM（±）-S-亚硝基-N-乙酰青霉胺（SNAP）使Vo增加了8%。cGMP合酶抑制剂0.01 mM Ly-83583使Vo降低了18%。cGMP类似物0.1 mM 8-溴-cGMP使Vo增加了17%。磷酸二酯酶的通用抑制剂0.02 mM 3-异丁基-1-甲基黄嘌呤（IBMX）使Vo增加了17%。cGMP磷酸二酯酶特异性抑制剂0.01 mM双嘧达莫使Vo增加了8%。除7-硝基吲唑和Ly-83583使最大等长力（F0）降低12%外，其他药物未改变最大等长力。在一氧化氮合酶抑制剂存在下，强直收缩肌肉中的cGMP水平降低了12% - 27%。我们得出结论，细胞内一氧化氮水平通过cGMP途径调节Vo。
