The Effect of L-arginine on Neointima Formation in a Rat Vascular Injury Model

ABSTRACT

BACKGROUND: The inhibitory effects of nitric oxide(NO) on platelet adhesion and vascular smooth muscle cell(VSMC) proliferation may have a possible role inhibiting development of neointima following balloon catheter induced injury. We tested the hypothesis that L-arginine, the precursor of NO, would attenuate neointima formation following balloon catheter induced injury via regulation of antagonistic balance between proliferation and apoptosis of VSMC. METHODS: Adult, male Sprague-Dawley rats(300 to 400g) were anesthetized with ketamine (100mg/kg intraperitoneally). The left common and external carotid artery were exposed. For endothelial denudation, 2mm angioplasty catheter was introduced through the left external carotid artery into the left common carotid artery. The catheter was inflated at I atm. and withdrawn three times. Animals were randomized to receive 2.25% L-arginine in their drinking water(n=14) or placebo(n=16) from 2 days prior to and 9 days following denudation. VSMC proliferation was quantified by immunohistochemical staining with an antibody to the proliferating cell nuclear antigen(PCNA). The cells undergoing apoptosis were identified by terminal nucleotidyl transferase-mediated nick end labeling(TUNEL) method and morphologic changes by computerized planimetry and transmission electron microscopy. RESULTS: 1) The neointimal area in injured arteries were significantly reduced in L-arginine supplemented animals compared with placebo group(p<0.05). 2) L-arginine administration significantly reduced the number of PCNA positive cells in neointima when compared with placebo at 9 days(p<0.05). 3) Positive TUNEL cells were not influenced by L-arginine supplementation. 4) On transmission electron microscopy, there were no cells showing characteristics of apoptosis in neointima. CONCLUSION: These results suggested that the inhibitory effect of L-arginine on neointima formation is due to reduced VSMC proliferation, but is not due to increased VSMC apoptosis at the early time period after initmal injur .