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

Research Project

Project/Area Number	06670734
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Circulatory organs internal medicine
Research Institution	FUKUSHIMA MEDICAL COLLEGE
Principal Investigator	MARUYAMA Yukio 1st.Dept.of Int.Med, Fukushima Medical College, Prof., 医学部・第一内科, 教授 (90004712)
Co-Investigator(Kenkyū-buntansha)	SAITO Tomiyoshi 1st.Dept.of Int.Med, Fukushima Medical College, Associate, 医学部・第一内科, 助手 (30235056)
Project Period (FY)	1994 – 1995
Project Status	Completed (Fiscal Year 1995)
Budget Amount *help	¥1,900,000 (Direct Cost: ¥1,900,000) Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000) Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywords	PTCA / intimal hyperplasia / L-arginine / Nitric Oxide / ACE inhibitor / 動脈硬化 / L-Arginino / D-Arginine / L-NAME
Research Abstract	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.