Sjakste Nikolajs, Baumane Larisa, Boucher Jean-Luc, Dzintare Maija, Meirena Dainuvite, Sjakste Jelizaveta, Lauberte Lasma, Kalvinsh Ivars
Faculty of Medicine, University of Latvia, and Latvian Institute of Organic Synthesis, Riga.
Basic Clin Pharmacol Toxicol. 2004 Jan;94(1):46-50.
Production of nitric oxide was measured in lipopolysaccharide-treated rats (10 mg/kg, 4 hr) using the electron paramagnetic resonance method. As compared to the control animals, the nitric oxide level in liver of lipopolysaccharide-treated rats increased from 27.6+/-4.7 to 1485+/-129 ng/g tissue, in heart from 4.8+/-0.7 to 271+/-26 ng/g tissue, in blood from 33.6+/-12.4 to 638+/-136 ng/g tissue, in kidney from 3.3+/-0.5 to 356+/-31 ng/g tissue, in brain cortex from 46.0+/-3.4 to 227+/-27 ng/g tissue, in cerebellum from 27.7+/-2.6 to 218+/-30 ng/g tissue, and in testes from 13.8+/-1.1 to 86+/-8 ng/g tissue. Administration of the antiischaemic drug, mildronate (120 mg/kg) caused a significant twofold decrease of the nitric oxide level in brain cortex and cerebellum 1 hr after drug administration. Its natural analogue gamma-butyrobetaine (30 mg/kg) triggered a twofold decrease of the nitric oxide concentration in all studied tissues 30 min. after the administration. Nitric oxide reached the initial level 2 hr later. Neither mildronate nor gamma-butyrobetaine could inhibit the inducible nitric oxide synthase in vitro. Analogues of gamma-butyrobetaine appear to be prospective drugs for the treatment of circulatory complications of sepsis.
采用电子顺磁共振方法测定脂多糖处理大鼠（10mg/kg，4小时）体内一氧化氮的生成量。与对照动物相比，脂多糖处理大鼠肝脏中的一氧化氮水平从27.6±4.7 ng/g组织增加到1485±129 ng/g组织，心脏中从4.8±0.7 ng/g组织增加到271±26 ng/g组织，血液中从33.6±12.4 ng/g组织增加到638±136 ng/g组织，肾脏中从3.3±0.5 ng/g组织增加到356±31 ng/g组织，大脑皮层中从46.0±3.4 ng/g组织增加到227±27 ng/g组织，小脑从27.7±2.6 ng/g组织增加到218±30 ng/g组织，睾丸从13.8±1.1 ng/g组织增加到86±8 ng/g组织。给予抗缺血药物米多君（120mg/kg）后1小时，大脑皮层和小脑中的一氧化氮水平显著降低了两倍。其天然类似物γ-丁甜菜碱（30mg/kg）在给药30分钟后使所有研究组织中的一氧化氮浓度降低了两倍。两小时后一氧化氮恢复到初始水平。米多君和γ-丁甜菜碱在体外均不能抑制诱导型一氧化氮合酶。γ-丁甜菜碱类似物似乎是治疗脓毒症循环并发症的潜在药物。
