Endothelial alterations in hypercholesterolemia: More than simply vasodilator dysfunction

Philip S. Tsao, John P. Cooke

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Occlusive vascular disease begins with an alteration of the endothelium, which is characterized by a decrease in nitric oxide (NO) activity. Endogenous NO inhibits many key processes in atherogenesis, including monocyte adherence, platelet activation, and smooth muscle proliferation. The mechanism by which NO activity is reduced in hypercholesterolemia and in other metabolic disorders associated with atherogenesis appears to be multifactorial. It includes increased production of oxygen-derived free radicals, alterations in NO synthase, and the accumulation of endogenous inhibitors (ADMA) of NO synthase. Plasma concentrations of ADMA are elevated in hypercholesterolemic humans. Elevated ADMA concentrations are associated with impaired endothelium-dependent, NO-mediated vasodilatation and reduced urinary nitrate exertion. These effects of ADMA are counteracted by administration of the NO precursor L-arginine. It is likely that basic insights regarding the mechanisms of endothelial dysfunction will lead to new therapeutic strategies for atherosclerosis.

Original languageEnglish (US)
JournalJournal of Cardiovascular Pharmacology
Volume32
Issue numberSUPPL. 3
StatePublished - Dec 1 1998

Keywords

  • Atherosclerosis
  • Hypercholesteremia
  • Nitric oxide
  • Nitric oxide synthase
  • Oxygen free radicals

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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