Local intramural delivery of L-arginine enhances nitric oxide generation and inhibits lesion formation after balloon angioplasty

Background Long-term oral administration of L-arginine has been shown to enhance production of nitric oxide (NO) and to reduce lesion formation. The goal of this study was to determine whether local intramural administration of L-arginine nine could enhance NO generation and reduce intimal thickening. Methods and Results New Zealand White rabbits (n=27) received a 1% cholesterol diet. For the short-term study, after 1 week of diet, both iliac arteries were balloon injured. Four weeks later, vasoreactivity was assessed angiographically during infusion of acetylcholine (Ach) before and after delivery of L-arginine or saline into the right or left iliac artery (800 mg/5 mL; 0.2 mL/min, 15 minutes) by use of a local drug-delivery balloon. Vessels were then harvested for measurements of NO. For the long-term study, after balloon injury, drugs were delivered as above into the iliac arteries. Two and 4 weeks after L-arginine delivery, vasoreactivity was determined. Subsequently, the iliac arteries were harvested for histomorphometric analysis and measurements of NO. In the short term study, local delivery of L-arginine restored endothelium-dependent vasodilatation (Ach 10(-5) mol/L; L-arginine +35+/-10%; saline -14+/-5%; P<.001) and enhanced local production of nitrogen oxides (L-arginine 152+/-28; saline 78+/-12 nmol/L per milligram of tissue per hour; P<.04). In the long-term study, local administration of L-arginine enhanced vascular NO production as long as 1 week after the injury (L-arginine 394.4+/-141.6; saline 86.3+/-34.3 nmol/L per milligram of tissue per hour; P<.01) and reduced intimal thickening 4 weeks later (intimal media ratio: L-arginine 0.56+/-0.1; saline 1.40+/-0.2; P<.001), largely due to suppression of macrophage accumulation. Conclusions A single intramural administration of L-arginine enhances vascular NO generation and inhibits lesion formation. Local augmentation of NO production at the site of balloon angioplasty may be a novel strategy to prevent restenosis.