The clinical pharmacology of L-arginine.
L-Arginine (2-amino-5-guanidinovaleric acid) is the precursor of nitric oxide, an endogenous messenger molecule involved in a variety of endothelium-mediated physiological effects in the vascular system. Acute and chronic administration of L-arginine has been shown to improve endothelial function in animal models of hypercholesterolemia and atherosclerosis. L-Arginine also improves endothelium-dependent vasodilation in humans with hypercholesterolemia and atherosclerosis. The responsiveness to L-arginine depends on the specific cardiovascular disease studied, the vessel segment, and morphology of the artery. The pharmacokinetics of L-arginine have recently been investigated. Side effects are rare and mostly mild and dose dependent. The mechanism of action of L-arginine may involve nitric oxide synthase substrate provision, especially in patients with elevated levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine. Endocrine effects and unspecific reactions may contribute to L-arginine-induced vasodilation after higher doses. Several long-term studies have been performed that show that chronic oral administration of L-arginine or intermittent infusion therapy with L-arginine can improve clinical symptoms of cardiovascular disease in man.
Böger
R H
RH
Institute of Clinical Pharmacology, Hannover Medical School, D-30623 Hannover, Germany.
Bode-Böger
S M
SM
D000818:Animals; D001120:Arginine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000502:physiology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*
D009569:Nitric Oxide; D001120:Arginine