Arginine restores nitric oxide activity and inhibits monocyte accumulation after vascular injury in hypercholesterolemic rabbits.
OBJECTIVE
This study sought to determine whether the alterations in vascular function and structure after balloon injury in hypercholesterolemic rabbits could be inhibited by dietary arginine.


BACKGROUND
Administration of arginine (the nitric oxide [NO] precursor) restores vascular NO activity in hypercholesterolemic animals. We and other investigators have shown that enhancement of vascular NO activity can inhibit myointimal hyperplasia after vascular injury in normocholesterolemic animals.


METHODS
Twenty-eight New Zealand White rabbits received either normal rabbit chow, 0.5% cholesterol diet or 0.5% cholesterol diet plus L-arginine hydrochloride (2.25% wt/vol) in the drinking water. After 6 weeks of dietary intervention, the left iliac artery of each animal was subjected to a balloon injury. Four weeks later, the iliac arteries were harvested for vascular reactivity studies and immunohistochemical analysis.


RESULTS
Vascular injury induced intimal thickening that was largely composed of vascular smooth muscle cells and extracellular matrix. In the setting of hypercholesterolemia, vascular injury induced an exuberant myointimal lesion that was augmented by the accumulation of lipid-laden macrophages. Dietary arginine reduced intimal thickening in the injured vessels of hypercholes-terolemic animals and substantially inhibited the accumulation of macrophages in the lesion (from 28% to 5% of the lesion area, p < 0.001).


CONCLUSIONS
We report that lesions induced by vascular injury in hypercholesterolemic animals are markedly reduced by oral administration of arginine. Moreover, we find that the nature of the lesion is altered, with a striking reduction in the percentage of macrophages comprising the lesion.
Section of Vascular Medicine, Stanford University, California 94305-5246, USA.
B Y
BY
Wang
R C
RC
Candipan
M
M
Arjomandi
P T
PT
Hsiun
P S
PS
Tsao
J P
JP
Cooke
D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D002404:Catheterization / Q000009:adverse effects*; D002455:Cell Division / Q000187:drug effects; D004032:Diet; D006937:Hypercholesterolemia / Q000378:metabolism / Q000473:pathology*; D006965:Hyperplasia / Q000473:pathology; D008264:Macrophages / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D011817:Rabbits
D009569:Nitric Oxide; D001120:Arginine