Guilmard C, Auguet M, Chabrier P E
Institut Henri Beaufour Research Laboratories, Les Ulis, France.
Nitric Oxide. 1998;2(3):147-54. doi: 10.1006/niox.1998.0170.
This study examines the ability of different nitric oxide synthase (NOS) inhibitors and NO donors to inhibit the endothelium-dependent relaxation of the rat aorta and the NANC relaxation of the rat gastric fundus. NG-Nitro-L-arginine, N-monomethyl-L-arginine, and S-methyl-L-thiocitrulline elicite comparable potency in the aorta and in the fundus. However, 1-(2-trifluoromethyl)imidazole (TRIM), unlike 7-nitroindazole, is more potent on the fundus than on the aorta, showing that TRIM elicits a selective functional inhibition of the neural NOS isoform. (1H)-(1,2,4)Oxadiazole(4,3-a)quinoxalin-1-one, a selective inhibitor of soluble guanylyl cyclase, inhibits the dilator response in both tissues and the cyclic GMP mimetic, 8-Br-cGMP, is 16 times more potent for inducing relaxation in the gastric fundus than in the aorta. However, methylene blue and LY-83583, two other inhibitors of soluble guanylyl cyclase and superoxide anion-generating agents, are at least 100 times less potent on fundus strips than on aortic rings. The data suggest that once released into the extracellular space, NO is more susceptible to inactivation by superoxide anions in the vascular tissue than in the gastric fundus. Thus, the study shows that selective inhibition of NO in a target tissue may be reached not only at the NOS isoform level but also by the manipulation of the NO pathway.
本研究考察了不同的一氧化氮合酶（NOS）抑制剂和一氧化氮供体抑制大鼠主动脉内皮依赖性舒张以及大鼠胃底非肾上腺素能非胆碱能（NANC）舒张的能力。NG-硝基-L-精氨酸、N-单甲基-L-精氨酸和S-甲基-L-硫代瓜氨酸在主动脉和胃底中显示出相当的效力。然而，1-（2-三氟甲基）咪唑（TRIM）与7-硝基吲唑不同，在胃底上比在主动脉上更有效，表明TRIM对神经型NOS同工型产生选择性功能抑制。（1H）-（1,2,4）恶二唑（4,3-a）喹喔啉-1-酮，一种可溶性鸟苷酸环化酶的选择性抑制剂，抑制两种组织中的舒张反应，而环鸟苷酸类似物8-溴-cGMP在胃底诱导舒张的效力比在主动脉中高16倍。然而，另外两种可溶性鸟苷酸环化酶抑制剂和超氧阴离子生成剂亚甲蓝和LY-8358在胃底条上的效力比在主动脉环上至少低100倍。数据表明，一旦释放到细胞外空间，一氧化氮在血管组织中比在胃底更容易被超氧阴离子灭活。因此，该研究表明，不仅可以在NOS同工型水平上，而且可以通过操纵一氧化氮途径来实现对靶组织中一氧化氮的选择性抑制。
