title: Therapeutic use of citrulline in cardiovascular disease.
abstract: L-citrulline is the natural precursor of L-arginine, substrate for nitric oxide synthase (NOS) in the production of NO. Supplemental administration L-arginine has been shown to be effective in improving NO production and cardiovascular function in cardiovascular diseases associated with endothelial dysfunction, such as hypertension, heart failure, atherosclerosis, diabetic vascular disease and ischemia-reperfusion injury, but the beneficial actions do not endure with chronic therapy. Substantial intestinal and hepatic metabolism of L-arginine to ornithine and urea by arginase makes oral delivery very ineffective. Additionally, all of these disease states as well as supplemental L-arginine enhance arginase expression and activity, thus reducing the effectiveness of L-arginine therapy. In contrast, L-citrulline is not metabolized in the intestine or liver and does not induce tissue arginase, but rather inhibits its activity. L-citrulline entering the kidney, vascular endothelium and other tissues can be readily converted to L-arginine, thus raising plasma and tissue levels of L-arginine and enhancing NO production. Supplemental L-citrulline has promise as a therapeutic adjunct in disease states associated with L-arginine deficiencies.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta GA, USA.
authors.forename: Maritza J
authors.initials: MJ
authors.lastname: Romero
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Platt
authors.forename: Ruth B
authors.initials: RB
authors.lastname: Caldwell
authors.forename: R William
authors.initials: RW
authors.lastname: Caldwell
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D002956:Citrulline / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism
chemical_list: D002956:Citrulline; D001120:Arginine