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Effects of nitric oxide on neointima formation after balloon arterial injury.

一氧化氮对球囊动脉损伤后新内膜形成的影响。

基本信息

批准号：
06670734
负责人：
MARUYAMA Yukio
金额：
$ 1.22万
依托单位：
FUKUSHIMA MEDICAL COLLEGE
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670734/
关键词：
PTCA intimal hyperplasia L-arginine Nitric Oxide ACE inhibitor 動脈硬化 L-Arginino D-Arginine L-NAME

项目摘要

We investigated the effect of nitric oxide (NO) on neointima formatin after balloon injury in rat carotid artery. Moreoverwe investigated the antiproliferative effect of L-Arginine (LARG,precursor of NO) and enalapril (ACE in hibitor) which was thought to stimulate NO formation via inhibition of kinin degradation. L-arginine, the same dose of D-arginine (DARG), L-NAME (inhibitor of NOS,NO syntase) or saline was administered intravenously to 12-week-old SD rats using osmotic pump during 14 days after balloon injury in rat carotid artery. Enalapril (orally), LARG and enalapril was administerd according to the same protocol. Then, these animals were sacrificed and perfusion fixed at pressure of 100 mmHg with 10% formaline. Serial cross sections were prepared from representative injured carotid artery. Area ratio of intima to media (I/M) was evaluated histopathologically. The I/M in the LARG group was lower than saline or DARG group, but that in L-NAME group was not higher than saline group. It suggested that endogeneous NO had not enough antiproliferative effect on the neointima although LARG had enough effect on that via NO production. Moreover the I/M in the combination of LARG and enalapril was lower than LARG or enalapril alone. In addition, immunostaining for inducible NOS was performed to each. Expression of inducible NOS in enalapril alone and combination of LARG and enalapril were much stronger than other group. These findings suggest that the combination of LARG and enalapril has much more powerfull antiproriferative effects on the neointima than LARG or enalapril alone and it was partly due to inducible NOS upregulation by enalapril.

本实验观察了一氧化氮（NO）在大鼠颈动脉球囊损伤后新生内膜形成中的作用。此外，我们研究了L-精氨酸（LARG，NO的前体）和依那普利（ACE抑制剂）的抗增殖作用，依那普利被认为通过抑制激肽降解来刺激NO的形成。12周龄SD大鼠颈总动脉球囊损伤后14 d内，用渗透泵分别静脉注射L-精氨酸、等剂量D-精氨酸（DARG）、L-NAME（NOS抑制剂，NO syntase）或生理盐水。依那普利（口服）、LARG和依那普利按相同方案给药。然后，将这些动物处死，并用10%福尔马林在100 mmHg的压力下灌注固定。从代表性损伤的颈动脉制备连续横截面。组织病理学观察内膜与中膜面积比（I/M）。LARG组的I/M值低于生理盐水组和DARG组，而L-NAME组的I/M值不高于生理盐水组。说明内源性NO对新生内膜的抗增殖作用不明显，LARG通过NO的产生对新生内膜的抗增殖作用较强。此外，LARG和依那普利组合的I/M低于LARG或依那普利单独。此外，对每种进行诱导型NOS的免疫染色。依那普利单用及LARG与依那普利合用组诱导型NOS的表达明显强于其他组。这些结果表明，LARG和依那普利的组合有更强大的抗增殖作用的新生内膜比LARG或依那普利单独，这是部分由于诱导型NOS上调依那普利。