L-arginine improves endothelium-dependent vasorelaxation and reduces intimal hyperplasia after balloon angioplasty

Reductions in nitric oxide (NO) activity persist after arterial intimal injury and may be a factor in the development of intimal hyperplasia. NO inhibits in vitro platelet aggregation, leukocyte adhesion, and smooth muscle cell growth, all of which are key components in the process of intimal hyperplasia. We hypothesized that long-term supplementation with L-arginine, the precursor of NO, would increase NO production and thereby improve endothelium-dependent vasorelaxation and simultaneously reduce intimal hyperplasia. Twenty-six New Zealand White male rabbits were fed standard rabbit chow either with or without 2.25% L-arginine in their drinking water for 3 weeks. Then the animals underwent unilateral iliac artery angioplasty and were continued on their respective diets. Four weeks after angioplasty, the iliac arteries were harvested for functional and morphometric studies. The iliac arteries from several animals from each group were processed for study by electron microscopy. Maximal endothelium-dependent vasorelaxation in injured arteries was significantly greater in L-arginine-supplemented animals (mean +/- SEM, 71.8 +/- 4.1%; n = 6) than controls (51.4 +/- 4.0%, n = 7; P < .05). Furthermore, the intimal area in injured arteries was significantly reduced in L-arginine-supplemented animals (0.22 +/- 0.03 mm2, n = 5) compared with controls (0.34 +/- 0.03 mm2, n = 6; P < .05). These data suggest that L-arginine supplementation enhances NO production at sites of vascular healing and may reduce intimal hyperplasia.