Oral
L-arginine improves cardiovascular function and reduces myocardial
ischemia in coronary artery patients
PUBLISHED CLINICAL ABSTRACT
BELOW
Tapiero
H, Mathe G, Couvreur P, Tew KD.
Faculte
de pharmacie, universite de Paris, CNRS UMR 8612, 5, rue Jean-Baptiste-Clement,
94200 Chatenay-Malabry, France. haimtapiero@aol.com
L-Arginine
(Arg) is classified as an essential amino acid for birds,
carnivores and young mammals and a conditionally essential
amino acid for adults. It is converted by arginase to L-ornithine,
a precursor of polyamines and urea, which is important in
the urea cycle. Arg serves as a precursor for creatine, which
plays an essential role in the energy metabolism of muscle,
nerve and testis and accounts for Arg catabolism and for the
synthesis of agmatine and proteins. Via its ability to increase
growth hormone secretion it influences immune function. Depending
on nutritional status and developmental stage, normal plasma
Arg concentrations in humans and animals range from 95 to
250 micromol/l. Systemic or oral Arg administration has been
shown to improve cardiovascular function and reduce myocardial
ischemia in coronary artery disease patients. It reduces blood
pressure and renal vascular resistance in essential hypertensive
patients with normal or insufficient renal function. Although
Arg plasma concentrations are not altered in hypercholesterolemic
individuals, oral or intravenous Arg administration can reverse
endothelial dysfunction in hypercholesterolemic patients and
in cigarette smokers. The main importance of Arg is attributed
to its role as a precursor for the synthesis of nitric oxide
(NO), a free radical molecule that is synthesized in all mammalian
cells from L-Arg by NO synthase (NOS). NO appears to be a
major form of the endothelium-derived relaxing factor (EDRF).
NO and EDRF share similar chemical and pharmacological properties
and are derived from the oxidation of a terminal guanidine
group of L-Arg. Various mechanisms have been implicated in
the defect in vascular relaxation. These include, increased
diffusional barrier for NO, L-Arg depletion, altered levels
of reactive oxygen, inactivation of NO by superoxide anions
(O2-). The independent reactions of O2-, NO and their reaction
yielding peroxynitrite are critical in the initiation and
maintenance of the atherosclerotic state and contribute to
the defect in vasorelaxation. NO also plays a role as a neurotransmitter,
mediator of immune response and as signaling molecule. The
NO synthesized by iNOS in macrophages contributes to their
cytotoxic activity against tumor cells, bacteria and protozoa.
