Salter M, Duffy C, Garthwaite J, Strijbos P J
Wellcome Research Laboratories, Beckenham, Kent, England.
J Neurochem. 1996 Apr;66(4):1683-90. doi: 10.1046/j.1471-4159.1996.66041683.x.
The ex vivo tissue concentration of nitrite and nitrate (NOx) was found to correlate closely with the activity of nitric oxide synthase (NOS; EC 1.14.13.39) in various brain regions. Systemic administration of the nonselective NOS inhibitor N omega-nitro-L-arginine (L-NA) at doses that completely inhibited both central and peripheral NOS, depleted whole-brain and CSF NOx by up to 75% but had no effect on plasma NOx. Selective inhibition of central NOS by intracerebroventricular administration of L-NA methyl ester produced similar decreases in levels of whole-brain NOx. A residual concentration of NOx of 10-15 microM remained in all brain regions even after complete inhibition of brain NOS. Brain NOx content decreased rapidly and in parallel with the inhibition of brain NOS. The ex vivo measurement of levels of brain NOx was found to reflect the in vivo efficacy of several different types of NOS inhibitor: L-NA, N omega-monomethyl-l-arginine, and 7-nitroindazole. Intraperitoneal administration of the NOS substrate L-arginine increased brain NOx concentrations by up to 150% of control values. These results demonstrate that the ex vivo measurement of levels of brain tissue NOx is a rapid, reliable, and straightforward technique to determine NOS activity in vivo. This method can be used to assess both the regional distribution and the degree of inhibition of NOS activity in vivo.
研究发现，亚硝酸盐和硝酸盐（NOx）的离体组织浓度与不同脑区一氧化氮合酶（NOS；EC 1.14.13.39）的活性密切相关。以完全抑制中枢和外周NOS的剂量全身给予非选择性NOS抑制剂Nω-硝基-L-精氨酸（L-NA），可使全脑和脑脊液中的NOx减少多达75%，但对血浆NOx无影响。通过脑室内给予L-NA甲酯选择性抑制中枢NOS，可使全脑NOx水平出现类似程度的下降。即使在脑NOS被完全抑制后，所有脑区仍残留10 - 15微摩尔的NOx浓度。脑NOx含量迅速下降，且与脑NOS的抑制情况平行。研究发现，脑NOx水平的离体测量反映了几种不同类型NOS抑制剂的体内疗效：L-NA、Nω-单甲基-L-精氨酸和7-硝基吲唑。腹腔注射NOS底物L-精氨酸可使脑NOx浓度增加至对照值的150%。这些结果表明，脑组织NOx水平的离体测量是一种快速、可靠且直接的体内测定NOS活性的技术。该方法可用于评估体内NOS活性的区域分布和抑制程度。
