title: Local intramural delivery of L-arginine enhances nitric oxide generation and inhibits lesion formation after balloon angioplasty.
abstract: 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 could enhance NO generation and reduce intimal thickening.
  
  
  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 (intima/ 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.
authors.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, CA 94305, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Schwarzacher
authors.forename: T T
authors.initials: TT
authors.lastname: Lim
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: R S
authors.initials: RS
authors.lastname: Kernoff
authors.forename: J
authors.initials: J
authors.lastname: Niebauer
authors.forename: J P
authors.initials: JP
authors.lastname: Cooke
authors.forename: A C
authors.initials: AC
authors.lastname: Yeung
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D002791:Cholesterol, Dietary / Q000633:toxicity; D004036:Diet, Atherogenic; D016503:Drug Delivery Systems; D007083:Iliac Artery / Q000187:drug effects* / Q000293:injuries; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002791:Cholesterol, Dietary; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine