Local L-arginine delivery after balloon angioplasty reduces monocyte binding and induces apoptosis

Background-Local administration of L-arginine after balloon angioplasty has been shown to enhance NO generation and inhibit lesion formation. In this study, we assessed the mechanisms by which local delivery of L-arginine inh ibits lesion formation. Methods and Results-New Zealand White rabbits (n=56) were fed a 1% choleste rol diet. After 1 week, both iliac arteries were balloon-denuded, and a loc al drug delivery catheter was introduced into both iliac arteries to delive r either L-arginine (800 mg/5 mt with and without 100 mu Ci L-[2,3-H-3] arg inine) or saline. Monocyte-endothelial interaction was assessed by function al binding assay; NO activity was measured by chemiluminescence. Intramural administration of radioactively labeled L-arginine led to significantly hi gher counts in comparison to the contralateral segment for up to 1 week aft er delivery (676+/-223 versus 453+/-93 cpm/mg; P<0.02); this was associated with significantly higher NO levels in the L-arginine-treated segments (39 4.4+/-141.6 versus 86.3+/-34.3 nmol/mg; P<0.01). Even after 2 to 3 weeks, m onocyte binding was significantly decreased by treatment with L-arginine as compared with saline infusion (P<0.01). After 3 weeks, there was a 9-fold greater number of apoptotic cells in the vessel wall of L-arginine as compa red with the saline-treated segments (P<0.05). Conclusions-Intramural delivery of L-arginine immediately after angioplasty causes a sustained increase in tissue L-arginine levels associated with en hancement of local NO synthesis. The local increase in NO synthesis is asso ciated with an attenuation of monocyte binding and increased apoptosis of r esident macrophages. This treatment strategy could be valuable for the prev ention and management of restenosis.