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L-Arginine is an essential amino acid for infants and
growing children, and it is a conditionally essential amino
acid for adult mammals, as it is important in situations in
which requirements exceed production,such as pregnancy.
[2] .
L-Arginine is a substrate for at least five enzymes identified
in mammals, including arginase,arginine-glycine
transaminase, kyotorphine synthase, nitric oxide synthase
(NOS) and arginine decarboxylase. [4] It has a significant
metabolic role as the product of ammonia detoxification, the
urea cycle metabolite, the precursor of proteins, ornithine,
urea and creatinine, and the amino acid involved in the
formation of active enzyme centers. [3] Its side effects are
rare and mostly mild and
dose-dependent. [1]
What is L-Arginine?
L-arginine is the substrate for the enzyme nitric oxide
synthase (NOS), which is responsible for the production of
nitric oxide (NO), an endogenous messenger molecule
involved in many of the processes associated with the
development of atherosclerosis.
Acute and chronic administration of L-arginine has been
shown to improve endothelial function in animal models of
hypercholesterolemia and atherosclerosis.
[1,4]
Researchers have debated whether dietary L-arginine
supplementation can provide valuable health benefits as it
augment NO production in man. In fact, some clinical
studies involving healthy volunteers or patients suffering
from hypertension and diabetes indicate that L-arginine
may also regulate vascular hemostasis. Futhermore,
animals and in vitro studies suggest that L-arginine may
have a complex antiaggregatory, anticoagulatory and
profibrinolytic effects. [1,3]
HOW DOES L-ARGININE BEEIFIT ENDOTHELIAL
DYSFUNCTION?
Diseases such as heart attack, stroke or critical
atherosclerotic leg ischaemia are very common and they
are the main cause of deaths in the age group over 40
years. Patients with advanced leg ischaemia can be treated
surgically. However in distal disseminated
occlusions, surgery is technically impossible.
It is believed that endothelium plays a crucial role in the
maintenance of vascular tone and structure. While, nitric
oxide (N)) is one of the major endothelium-derived
vasoactive mediators; an endogenous messenger molecule
formed in healthy vascular endothelium from the amino acid
precursor L-arginine. Endothelial dysfunction is caused by
various cardiovascular risk factors, metabolic diseases,
systemic or local inflammation. One mechanism that
explains the occurrence of endothelial dysfunction is the
presence of elevated blood levels of asymmetric
dimethylarginine (ADMA)--an L-arginine analogue that
inhibits NO formation and thereby can impair vascular
function. Supplementation with L-arginine has been shown
to increase of nitric oxide synthesis, restore vascular
function and to improve the clinical symptoms of various
diseases associated with vascular dysfunction. [5,6] Poland
researchers suggest that the clinical effectiveness of
L-arginine is comparable to conventional pharmacotherapy;
L-arginine supplementation may contribute to better results
of atherosclerosis treatment.
HOW DOES L-ARGININE IMROVE THE ENDOTHELIAL
NITRIC OXIDE BIOACTIVITIES?
The mechanisms by which L-arginine improves endothelial
nitric oxide bioactivity include increased intracellular uptake
via the high-affinity cationic transporter; substrate
competition with asymmetric dimethylarginine, a naturally
occurring inhibitor of nitric oxide synthase; direct antioxidant
activity; stimulated release of histamine from mast cells,
which produces a vasodilator response; decreased activity
of norepinephrine, which promotes the effect of
endogenous vasodilators including nitric oxide; and
increased insulin secretion, which causes vasodilation. [8, 9]
Researchers also believe that L-arginine metabolites may
have some benefits on renal disease. It is because
administration of exogenous L-arginine protected some
subjects in ischemic acute renal failure. [7] Infusion of
L-arginine in experimental animals increases renal plasma
flow (RPF) and glomerular filtration rate (GFR). Despite
persistent hyperglycemia, the administration of L-arginine is
also found to prevent the development of hyperfiltration and
ameliorated proteinuria in diabetic rats. [10]
SIDE EFFECTS OF L-ARGININE
A few studies suggest the side effect of L-arginine
supplementation is mild and dose-dependent. However,
High dose of L-arginine intraperitoneal administration has
been reported to cause side effects, such as pancreatitis.
[11]
COMMENT
This article summarizes only 11 of the most recent review
articles on the uses of L-arginine on certain conditions.
L-arginine may have much more benefits (side effects as
well) on various conditions.
THIS ARTICLE IS FOR YOUR REFERENCE ONLY. IF YOU HAVE
ANY QUESTION, PLEASE, CONSULT WITH YOUR DOCTOR. ALL
RIGHTS RESERVED 2008 ZHION
[1] Bode-Boger SM. Influence of L-arginine on development of
atherosclerosis: what is the therapeutically assured? Dtsch Med
Wochenschr. 2005 Mar 18;130(11):593-8. [2] Bronte V et al,
Regulation of immune responses by L-arginine metabolism. Nat Rev
Immunol. 2005 Aug;5(8):641-54. [3] Cylwik D, et al, L-arginine and
cardiovascular system. Pharmacol Rep. 2005 Jan-Feb;57(1):14-22.
[4] Nakaki T, Kato R. Beneficial circulatory effect of L-arginine. Jpn J
Pharmacol. 1994 Oct;66(2):167-71. [5] Boger RH, L-Arginine
improves vascular function by overcoming deleterious effects of
ADMA, a novel cardiovascular
risk factor. Altern Med Rev. 2005 Mar;10(1):14-23. [6] Kielar M, et al,
New possibilities in treatment of atherosclerosis--increase of nitric
oxide synthesis by L-arginine supplementationPol Merkuriusz Lek.
2004 Dec;17(102):656-60. [7] Cherla G, Role of L-arginine in the
pathogenesis and treatment of renal disease. J Nutr. 2004
Oct;134(10 Suppl):2801S-2806S; discussion 2818S-2819S. [8]
Loscalzo J. L-arginine and
atherothrombosis. J Nutr. 2004 Oct;134(10 Suppl):2798S-2800S;
discussion 2818S-2819S. [9] Stuehr DJ. Enzymes of the L-arginine to
nitric oxide pathway. J Nutr. 2004 Oct;134(10 Suppl):2748S-2751S;
discussion 2765S-2767S. [10] Klahr S, et al, L-arginine as a
therapeutic tool in kidney disease. Semin Nephrol. 2004
Jul;24(4):389-94. [11] Hegyi P,
L-arginine-induced experimental pancreatitis. World J Gastroenterol.
2004 Jul 15;10(14):2003-9.