L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans

Mark A. Creager, Shelly J. Gallagher, Xavier J. Girerd, Sharon M. Coleman, Victor J. Dzau, John P. Cooke

Research output: Contribution to journalArticlepeer-review

702 Scopus citations


Endothelium-dependent vasodilation is impaired in hypercholesterolemia, even before the development of atherosclerosis. The purpose of this study was to determine whether infusion of L-arginine, the precursor of the endothelium-derived relaxing factor, nitric oxide, improves endothelium-dependent vasodilation in hypercholesterolemic humans. Vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 2.76±0.10mmol/liter) and 14 age-matched patients with hypercholesterolemia (serum LDL cholesterol = 4.65±0.36 mmol/liter, P < 0.05). The vasodilative response to the endothelium-dependent vasodilator, methacholine chloride, was depressed in the hypercholesterolemic group, whereas endothelium-independent vasodilation, induced by nitroprusside, was similar in each group. Intravenous administration of L-arginine augmented the forearm blood flow response to methacholine in the hypercholesterolemic individuals, but not in the normal subjects. L-arginine did not alter the effect of nitroprusside in either group. D-arginine had no effect on forearm vascular reactivity in either group. It is concluded that endothelium-dependent vasodilation is impaired in hyper-cholesterolemic humans. This abnormality can be improved acutely by administration of L-arginine, possibly by increasing the synthesis of endothelium-derived relaxing factor.

Original languageEnglish (US)
Pages (from-to)1248-1253
Number of pages6
JournalJournal of Clinical Investigation
Issue number4
StatePublished - Oct 1992


  • Cholesterol
  • Endothelium
  • Endothelium-derived relaxing factor
  • L-arginine
  • Limb blood flow

ASJC Scopus subject areas

  • Medicine(all)


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