Therapeutic use of citrulline in cardiovascular disease

Research output: Contribution to journalReview article

121 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)275-290
Number of pages16
JournalCardiovascular Drug Reviews
Volume24
Issue number3-4
DOIs
StatePublished - Sep 1 2006

Fingerprint

Citrulline
Therapeutic Uses
Arginine
Cardiovascular Diseases
Arginase
Diabetic Angiopathies
Ornithine
Liver
Vascular Endothelium
Reperfusion Injury
Nitric Oxide Synthase
Intestines
Urea
Atherosclerosis
Therapeutics
Heart Failure
Hypertension
Kidney

Keywords

  • Arginase
  • Arginine
  • Citrulline
  • NO
  • Nitric oxide synthase
  • Oxidative stress
  • Vascular endothelial dysfunction

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Therapeutic use of citrulline in cardiovascular disease. / Romero, Maritza J.; Platt, Daniel H.; Caldwell, Ruth B.; Caldwell, R. William.

In: Cardiovascular Drug Reviews, Vol. 24, No. 3-4, 01.09.2006, p. 275-290.

Research output: Contribution to journalReview article

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