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

研究了一氧化氮（NO）对大鼠颈动脉球囊损伤后新生内膜形成的影响。此外，我们还研究了l -精氨酸（LARG， NO的前体）和依那普利（ACE抑制剂）的抗增殖作用，它们被认为是通过抑制激肽降解来刺激NO的形成。12周龄SD大鼠颈动脉球囊损伤后第14天，采用渗透泵静脉注射l -精氨酸、等量d -精氨酸（DARG）、L-NAME （NOS、NO合酶抑制剂）或生理盐水。依那普利（口服）、LARG和依那普利按照相同的方案给药。然后处死这些动物，用10%福尔马林在100 mmHg压力下灌注固定。对具有代表性的颈动脉损伤进行了连续横切面制备。组织病理学评估内膜与中膜面积比（I/M）。LARG组I/M低于生理盐水组或DARG组，L-NAME组I/M不高于生理盐水组。提示LARG通过NO的产生对新生内膜有一定的抑制作用，但内源性NO对新生内膜的抑制作用不够。LARG联合依那普利的I/M值低于LARG或依那普利单用。并对各组进行诱导NOS免疫染色。依那普利单用组和LARG与依那普利联用组诱导型NOS的表达明显强于其他组。上述结果提示LARG联合依那普利对新生内膜的抗增殖作用比LARG或依那普利单用更强，其部分原因是依那普利诱导NOS上调。

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.