765-2 Dietary L-Arginine Attenuates Macrophage Infiltration and Intimal Hyperplasia After Balloon Injury

Abstract

Balloon injury in arteries of hypercholesterolemic animals creates a myointimal lesion that is comprised of macrophages as well as vascular smooth muscle cells. We have shown that chronic administration of L-arginine (Arg) enhances endothelial NO production and inhibits both monocyte-vessel wall interaction and plaque formation. Accordingly, we hypothesized that dietary Arg would reduce lesion formation and macrophage infiltration in hypercholesterolemic animals following balloon injury. NZW rabbits were divided into 3 groups: Normal chow (N), 0.5% cholesterol (Chol), or 0.5% Chol + 2.25% Arg supplementation. Treatment was initiated 6 weeks prior to balloon injury of the left iliac artery. Four weeks after injury, the iliacs were harvested for: assessment of endothelium-dependent relaxation by vasodilation to acetylcholine; histology; and immunohistochemistry to assess macrophage infiltration. Endothelium-dependent relaxation was impaired following injury in the Chol and Arg groups (32 v 4 v 2%, N v Chol v Arg). In the contralateral non-injured arteries, Arg treatment restored endotheliumdependent relaxation (79 v 44 v 64%, N v Chol v Arg). The Chol group showed a 2.5-fold increase in intimal area following injury compared with N, while Arg attenuated lesion formation (0.28 v 0.69 v 0.34 mm 2 , N v Chol v Arg, p < 0.01). Area involved by macrophage increased in the Chol iliacs compared with N, while Arg significantly attenuated macrophage infiltration (2 v 28 v 5%, N v Arg v Chol, p < 0.001). Chronic arginine supplementation reduces intimal proliferation and attenuates macrophage infiltration following balloon injury in hypercholesterolemic animals, and is associated with restored NO-dependent vasodilation.