NG-monomethyl-L-arginine paradoxically relaxes preconstricted canine intrapulmonary arteries.
NG-monomethyl-L-arginine paradoxically relaxes preconstricted canine intrapulmonary arteries.
复制标题
NG-单甲基-L-精氨酸反而可以放松预先收缩的犬肺内动脉。
DOI：
10.1152/jappl.1993.74.2.549
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Tod,ML
中科院分区：
文献类型：
--
作者：
Tseng,CM;Goodman,LW;Rubin,LJ;Tod,ML
我们研究了一氧化氮（NO）合成抑制剂ng - monom甲基- l-精氨酸（LMMA）对因苯肾上腺素收缩的犬肺内动脉的影响。将分离的血管悬浮在含有改良克雷布斯溶液的器官室中，记录等长张力。与其他研究预测的预期收缩相反，LMMA反而在苯肾上腺素收缩的犬肺动脉中引起剂量依赖性血管松弛。LMMA（1和10微米）分别使苯肾上腺素收缩率降低5%和23%。ng -单甲基-d -精氨酸（DMMA）也有类似的剂量依赖性松弛，但l-精氨酸（L-Arg）、N - epsilon-甲基-l -赖氨酸和另一种NO合成抑制剂N - omega-硝基-l -精氨酸（LNA）则没有，这表明位于胍-氮上的甲基在这些反应中很重要。NO前体l -精氨酸预处理对LMMA和DMMA诱导的血管松弛无影响；然而，不同的环加氧酶抑制剂吲哚美辛（10微米）和甲氯芬酯（2微米）消除了反应。用LNA（100微米）预处理血管增强了lmma诱导的松弛，但减弱了dmma诱导的反应。在内皮摩擦血管中也观察到LMMA和dmma诱导的血管松弛；dmma诱导的血管舒张在有内皮和无内皮的血管中相似，而lmma诱导的血管舒张在有内皮的血管中增加。这些数据表明，LMMA和DMMA通过引起扩张前列腺素的合成来诱导血管舒张，而不依赖于内皮细胞的存在和L-Arg-NO途径。此外，内皮去除和LNA预处理均增强了LMMA诱导的血管松弛，而非dmma诱导的血管松弛，这表明LMMA对NO合成的抑制与其环氧化酶依赖性血管松弛作用相反。
We studied the effects of NG-monomethyl-L-arginine (LMMA), a nitric oxide (NO) synthesis inhibitor, in canine intrapulmonary arteries constricted with phenylephrine. Isolated vessels were suspended in organ chambers containing modified Krebs solution, and isometric tensions were recorded. In contrast to the expected constriction predicted from other studies, LMMA instead caused dose-dependent vasorelaxation in phenylephrine-constricted canine pulmonary arteries. LMMA (1 and 10 microM) reduced the phenylephrine contraction by 5 and 23%, respectively. Similar dose-dependent relaxations were observed with NG-monomethyl-D-arginine (DMMA) but not with L-arginine (L-Arg), N epsilon-methyl-L-lysine, and another NO synthesis inhibitor, N omega-nitro-L-arginine (LNA), suggesting that a methyl group positioned at the guanidino-nitrogen is important in these responses. Vasorelaxation induced by LMMA and DMMA was not affected by pretreatment with the NO precursor L-Arg; however, responses were abolished by dissimilar cyclooxygenase inhibitors indomethacin (10 microM) and meclofenamate (2 microM). Pretreatment of vessels with LNA (100 microM) augmented LMMA-induced relaxations but attenuated DMMA-induced responses. LMMA- and DMMA-induced vasorelaxations were also observed in endothelium-rubbed vessels; DMMA-induced vasorelaxations were similar in vessels with and without endothelium, whereas LMMA-induced relaxations were increased in endothelium-rubbed vessels. These data suggest that LMMA and DMMA induced vasorelaxation by causing synthesis of dilator prostaglandins, which was independent of the presence of endothelial cells and the L-Arg-NO pathway. In addition, both endothelium removal and LNA pretreatment augmented LMMA-induced but not DMMA-induced relaxations, suggesting that inhibition of NO synthesis by LMMA opposes its cyclooxygenase-dependent vasorelaxant effects.