再生内皮细胞中一氧化氮合成内源性抑制剂的积累及L-精氨酸含量的降低。

Accumulation of endogenous inhibitors for nitric oxide synthesis and decreased content of L-arginine in regenerated endothelial cells.

Azuma H, Sato J, Hamasaki H, Sugimoto A, Isotani E, Obayashi S

Department of Medicinal Chemistry, Tokyo Medical and Dental University, Japan.

Br J Pharmacol. 1995 Jul;115(6):1001-4. doi: 10.1111/j.1476-5381.1995.tb15910.x.

Abstract

We examined regeneration of endothelial cells (ECs), neointima formation, decreased endothelium-dependent relaxation (EDR) and changes in the contents of L-arginine, NG-monomethyl-L-arginine (L-NMMA), asymmetrical NG, NG-dimethylarginine (ADMA) and symmetrical NG,NG-dimethylarginine (SDMA) in the regenerated ECs, 6 weeks after balloon denudation of the rabbit carotid artery. 2. Regeneration of ECs was completed in 6 weeks and a significant neointima formation accompanied by the decreased EDR was observed. 3. L-NMMA and ADMA contents in the regenerated ECs (23.5 +/- 4.3 and 21.2 +/- 2.0 pmol mg-1 DNA, respectively) were significantly (P < 0.05 and P < 0.01) higher than those in the control ECs (8.8 +/- 3.0 and 7.4 +/- 1.9 pmol mg-1 DNA, respectively), whereas L-arginine was significantly (P < 0.005) decreased in the regenerated ECs (31,470 +/- 1,050 pmol mg-1 DNA) as compared to that in the control ECs (47,870 +/- 1,890 pmol mg-1 DNA). SDMA content was below the assay limits. 4. L-NMMA and ADMA, but not SDMA, inhibited the EDR induced by acetylcholine in a concentration-dependent manner. The inhibition with L-NMMA and ADMA was prevented by an addition of L-arginine, but not by D-arginine. 5. These results suggest that the accumulation of endogenous inhibitors for nitric oxide synthesis and decreased L-arginine content are associated with decreased NO production/release from regenerated ECs and neointima formation.

摘要

我们检测了兔颈动脉球囊剥脱术后6周时，再生内皮细胞（ECs）的再生情况、新生内膜形成、内皮依赖性舒张功能（EDR）降低以及再生ECs中L-精氨酸、NG-单甲基-L-精氨酸（L-NMMA）、不对称NG，NG-二甲基精氨酸（ADMA）和对称NG，NG-二甲基精氨酸（SDMA）含量的变化。2. ECs的再生在6周内完成，观察到明显的新生内膜形成并伴有EDR降低。3. 再生ECs中L-NMMA和ADMA的含量（分别为23.5±4.3和21.2±2.0 pmol mg-1 DNA）显著高于对照ECs（分别为8.8±3.0和7.4±1.9 pmol mg-1 DNA）（P<0.05和P<0.01），而与对照ECs（47,870±1,890 pmol mg-1 DNA）相比，再生ECs中L-精氨酸显著降低（P<0.005）（31,470±1,050 pmol mg-1 DNA）。SDMA含量低于检测限。4. L-NMMA和ADMA而非SDMA以浓度依赖性方式抑制乙酰胆碱诱导的EDR。添加L-精氨酸可阻止L-NMMA和ADMA的抑制作用，但添加D-精氨酸则不能。5. 这些结果表明，一氧化氮合成内源性抑制剂的积累和L-精氨酸含量降低与再生ECs中一氧化氮产生/释放减少及新生内膜形成有关。