Endothelial dysfunction: clinical strategies for treating oxidant stress.
BACKGROUND
A growing body of evidence has demonstrated that oxidants play a critical role in the pathogenesis of endothelial dysfunction. Pathologic processes fundamental to development and progression of endothelial dysfunction such as the oxidation of LDL, the loss of bioavailable nitric oxide, and the vascular inflammatory response are all modulated by oxidant stress. Therapeutic strategies to reverse endothelial dysfunction have begun to focus on agents with the ability to ameliorate oxidant stress.


METHODS
Preclinical and clinical studies evaluating the actions of antioxidants as well as traditional cardiovascular therapies in ameliorating oxidative stress and endothelial dysfunction were reviewed through the use of a MEDLINE search of English language articles published between the years of 1992 and 2002.


RESULTS
Antioxidants appear to be an attractive candidate therapy, yet despite compelling preclinical evidence supporting their benefits, efforts to validate the use of vitamins C and E in a clinical setting have been conflicting. In contrast, conventional cardiovascular therapies such as ACE inhibitors, statins, insulin-sensitizing agents, and estrogens have been shown to alleviate endothelial dysfunction, often independent of their effects on systemic disease processes.


CONCLUSIONS
These agents restore endothelial function through their salutary effects on pathologic vascular oxidative processes.
Fenster
Brett E
BE
Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, Calif 94305, USA.
Tsao
Philip S
PS
Rockson
Stanley G
SG
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D020138:Hyperhomocysteinemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D014652:Vascular Diseases / Q000188:drug therapy*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents