From: Doug Skrecky (oberon@vcn.bc.ca)
Date: Thu Jul 08 1999 - 01:00:39 MDT
Authors
Boger RH. Bode-Boger SM. Brandes RP. Phivthong-ngam L. Bohme M. Nafe R.
Mugge A. Frolich JC.
Institution
Institute of Clinical Pharmacology, Medical School, Hannover, Germany.
Title
Dietary L-arginine reduces
the progression of atherosclerosis in cholesterol-fed rabbits: comparison
with lovastatin.
Source
Circulation. 96(4):1282-90, 1997 Aug 19.
Abstract
BACKGROUND: We investigated whether L-arginine induces
regression of preexisting atheromatous lesions and reversal of endothelial
dysfunction in hypercholesterolemic rabbits, whether similar effects can be
obtained by cholesterol-lowering therapy with lovastatin, and which mechanism
leads to these effects. METHODS AND RESULTS: Rabbits were fed 1% cholesterol
for 4 weeks and 0.5% cholesterol for an additional 12 weeks. Two groups of
cholesterol-fed rabbits were treated with L-arginine (2.0%
in drinking water) or lovastatin (10 mg/d) during weeks 5 through 16.
Systemic nitric oxide (NO) formation was assessed as the urinary excretion
rates of nitrate and cGMP in weekly intervals. Cholesterol feeding
progressively reduced urinary nitrate excretion to approximately 40% of
baseline (P<.05) and increased plasma concentrations of asymmetrical
dimethylarginine (ADMA), an endogenous NO synthesis inhibitor.
Dietary L-arginine reversed the reduction
in plasma L-arginine/ADMA ratio and partly restored urinary
excretion of nitrate and cGMP (each P<.05 vs cholesterol) but did not change
plasma cholesterol levels. L-Arginine completely blocked the
progression of carotid intimal plaques, reduced aortic intimal thickening,
and preserved endothelium-dependent vasodilator function. Lovastatin
treatment reduced plasma cholesterol by 32% but did not improve urinary
nitrate or cGMP excretion or endothelium-dependent vasodilation. Lovastatin
had a weaker inhibitory effect on carotid plaque formation and aortic intimal
thickening than L-arginine. L-Arginine
inhibited but lovastatin potentiated superoxide radical generation in the
atherosclerotic vascular wall. CONCLUSIONS: Dietary
L-arginine improves NO-dependent vasodilator function in
cholesterol-fed rabbits and completely blocks the progression of plaques via
restoration of NO synthase substrate availability and reduction of vascular
oxidative stress. Lovastatin treatment has a weaker inhibitory effect on the
progression of atherosclerosis and no effect on vascular NO elaboration,
which may be due to its stimulatory effect on vascular superoxide radical
generation.
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