Effects of L-arginine on vascular smooth muscle cell proliferation and apoptosis after balloon injury

Nitric oxide (NO) inhibits neointimal formation in experimental models of r estenosis, but: the mechanisms have not been fully elucidated. This study e xamined whether the beneficial effect of L-arginine, the physiological NO p recursor, was associated with alteration of the apoptotic and proliferative activities of vascular smooth muscle cells (VSMCs) in the vessel wall afte r arterial injury. Balloon injury was performed in the rat carotid-artery i njury model. Rats were treated with L-arginine (2.25% in the drinking water ) or normal drinking water, and sacrificed at 1, 2 and 14 days postinjury. Apoptosis was assessed by terminal deoxynucleotidyl transferase mediated dU TP-biotin nick-end labeling (TUNEL), and proliferation by proliferating cel l nuclear antigen (PCNA) immunohistochemistry. Treatment with L-arginine in creased the luminal area at 14 days postinjury (0.26 +/- 0.03 mm(2) vs 0.14 +/- 0.04 mm(2); p < 0.05), and this effect was attributable to a reduction in neointimal formation (0.11 +/- 0.03 mm(2) vs 0.23 +/- 0.04 mm(2); p < 0 .05), while L-arginine did not affect vascular remodeling, as indicated by the total vessel area. The decreased neointimal area at 14 days after ballo on injury contained a reduced percentage of TUNEL positive (0.1 +/- 0.1% vs 2.0 +/- 0.6%; p < 0.05), and PCNA positive (13.0 +/- 2.6% vs 27.2 +/- 5.9% ; p < 0.05) nuclei, respectively. L-arginine did not influence the apoptoti c or proliferative activities of VSMCs at earlier time points postinjury. T he favourable effect of L-arginine in the Mt model of arterial injury is as sociated with inhibition of VSMC proliferative activity in the vessel wall and is not explained by increased VSMC apoptosis.