Author + information
- Received April 12, 1995
- Revision received June 27, 1996
- Accepted July 10, 1996
- Published online November 15, 1996.
- Bing-Yin Wang, MD, PhD,
- Robert C. Candipan, MD, PhD,
- Mehrdad Arjomandi, BS,
- Paul T.C. Hsiun, BS,
- Philip S. Tsao, PhD and
- John P. Cooke, MD, PhD, FACC1
- ↵1Address for correspondence:: Dr. John P. Cooke, Division of Cardiovascular Medicine, Stanford University Medical School, 300 Pasteur Drive, Stanford, California 94305-5246.
Objectives. 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 hypercholesterolemic 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.
☆ This work was supported in part by Grant 1R01HL48638 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland and was performed during the tenure of a Grant-in-Aid Award from the American Heart Association, Dallas, Texas and Sanofi Winthrop, Redwood City, California. Dr. Wang is the recipient of a Ho Tim-Stanley Ho-Li Shing Award from the Stanford University-Asia Medical Fund, Stanford, California. Mr. Arjomandi and Mr. Hsiun are Stanford Medical Scholars. Drs. Tsao and Candipan are recipients of National Service Research Awards. Dr. Cooke is a recipient of the Vascular Academic Award from the National Heart, Lung, and Blood Institute (1K07HC02660) and is an Established Investigator of the American Heart Association.
- Received April 12, 1995.
- Revision received June 27, 1996.
- Accepted July 10, 1996.