Circulation, Vol 90, 1357-1362, Copyright © 1994 by American Heart Association
M Hamon, B Vallet, C Bauters, N Wernert, EP McFadden, JM Lablanche, B Dupuis and ME Bertrand
BACKGROUND: Nitric oxide (NO), in addition to its potent vasorelaxant
properties, may participate in growth regulation of cultured smooth muscle
cells. It was recently demonstrated that in vivo endothelial injury induces
the production of NO from L-arginine in the arterial wall. METHODS AND
RESULTS: We studied the effects of long-term administration of L-arginine,
the precursor of NO, on neointimal thickening and on
neoendothelium-dependent vasorelaxation 4 weeks after balloon denudation of
normocholesterolemic rabbit iliac arteries. Rabbits were fed with either a
standard diet or a diet supplemented with L-arginine (2.25%) in their
drinking water 3 days before and during 4 weeks after balloon denudation.
The effectiveness of L- arginine supplementation was confirmed by
measurement of plasma arginine levels. L-Arginine had no effect on
hemodynamic parameters. All animals were killed 4 weeks after balloon
denudation, and a digital histomorphometric analysis of three serial
nonconsecutive histological cross sections per iliac artery was performed.
Intimal thickening was reduced (P < .05) from 0.43 +/- 0.08 (SE) mm2 in
controls (n = 8) to 0.24 +/- 0.02 mm2 in treated animals (n = 8). Ten
animals (n = 5 in each group) were used for in vitro vasoreactivity
assessment 4 weeks after balloon denudation. Neoendothelium-dependent
acetylcholine- induced relaxation (10(-8) mol/L to 3.10(-5) mol/L) in
treated animals (Emax = -24.1 +/- 5.5%) was significantly greater than in
controls (Emax = -8.9 +/- 2.2%). Endothelium-independent relaxation did not
differ between groups (Emax = -58.1 +/- 6.5% in L-arginine-supplemented
animals versus -52.9 +/- 6.8% in controls). CONCLUSIONS: Our results
demonstrate that L-arginine, a precursor of NO, reduces neointimal
thickening after balloon denudation and improves neoendothelial- dependent
acetylcholine-induced relaxation.
ARTICLES
Long-term oral administration of L-arginine reduces intimal thickening and enhances neoendothelium-dependent acetylcholine-induced relaxation after arterial injury
Department of Cardiology, University of Lille, France.
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