We have previously demonstrated in hypercholesterolemic animals that supplemental arginine (ARG) restores endothelium-deried nitric oxide (EDNO) activity and induces regression of preexisting intimal lesions. This effect is mediated by the metabolism of ARG to NO. In this study we tested the hypothesis that restoration of EDNO activity would attenuate monocyte-endothelial interaction in animals with chronic hypercholesterolemia. Male NZW rabbits (n=36) were fed normal chow (N; n=6) or a 0.5% cholesterol diet for 10 weeks. After 10 weeks hypercholesterolemic animals were then supplemented with ARG (2.25%) (n=16) or vehicle (C; n=14). Thoracic aortae were harvested at 12 and 14 weeks. NO-dependent vasodilation as assessed by the maximal relaxation to acetylcholine was significantly reduced in group C (C vs N: 37% vs 73%; p<0.01) which was partially restored in group ARG (ARG vs C: 60% vs 73%; p<0.01). in a subgroup (n=17) monocyte-endothelial binding was assessed. Thoracic aortae were opened longitudinally, exposed to medium containing fluorescently labeled mouse monocytoid cells (WEHI 78/24), and counted by epifluorescent microscopy. Monocytoid cell binding was significantly reduced by supplemental ARG (ARG vs C: 56±18 vs 114±44; p<0.003). In conclusion, restoration of EDNO in animals with chronic hypercholesterolemia is associated with a marked attenuation of monocyte-endothelial interaction.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - 1996|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)