Journal
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
Volume 55, Issue 4, Pages 308-316Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FJC.0b013e3181d89670
Keywords
diabetes; hypertension; oxidants; nitric oxide; nitrotyrosine; protein oxidation
Funding
- NHLBI NIH HHS [P01 HL081587-05, P01 HL068758-06A1, R01 HL031607-26A1, P01 HL081587, R01 HL031607, P01 HL068758] Funding Source: Medline
- NIA NIH HHS [R01 AG027080, R01 AG027080-05, R01 AG27080] Funding Source: Medline
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Vascular disease in hypertension and diabetes is associated with increased oxidants. The oxidants arise from NADPH oxidase, xanthine oxidase, and mitochondria. Superoxide anion and hydrogen peroxide are produced by both leukocytes and vascular cells. Nitric oxide is produced in excess by inducible nitric oxide synthase, and the potent oxidant, peroxynitrite, is formed from superoxide and nitric oxide. The damage to proteins caused by oxidants is selective, affecting specific oxidant-sensitive amino acid residues. With some important vascular proteins, for example, endothelial nitric oxide synthase, prostacycline synthase, and superoxide dismutase, oxidation of a single susceptible amino acid inactivates the enzyme. The beneficial effects of antioxidants, at least in animal models of hypertension and diabetes, can in part be ascribed to protection of these and other proteins. Mutant proteins lacking their reactive constituent can recapitulate some disease phenotypes suggesting a pathogenic role of the oxidation. Thus, many of the shared functional abnormalities of hypertensive and diabetic blood vessels may be caused by oxidants. Although studies using antioxidants have failed in patients, the successful treatment of vascular disease with HMG-CoA reductase inhibitors, thromboxane A(2) antagonists, and polyphenols may depend on their anti-inflammatory effects and ability to decrease production of damaging oxidants.
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