Effect of vitamin C on the availability of tetrahydrobiopterin in human endothelial cells

Timothy A. Baker, Sheldon Milstien, Zvonimir S. Katusic

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


Vitamin C has long been known for its beneficial vascular effects, but its mechanism of action remains unclear. Recent reports suggest that vitamin C may prevent endothelial dysfunction by scavenging free radicals and increasing the bioavailability of nitric oxide. To investigate this area further, we studied the effect of vitamin C (10-4 M) and Mn(III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP; 10-5 M), a scavenger of superoxide, hydrogen peroxide, and peroxynitrite, on endothelial nitric oxide synthase (eNOS) enzymatic activity in cultured human umbilical vein endothelial cells. L-Citrulline formation (a measure of eNOS enzymatic activity) was significantly increased in cells treated for 24 h with vitamin C. No effect was observed after MnTBAP treatment. Chronic administration of vitamin C also had no effect on eNOS protein expression. Treatment with vitamin C for 24 h significantly increased levels of the eNOS co-factor tetrahydrobiopterin (BH4), whereas MnTBAP did not affect its levels. Sepiapterin (10-4 M), a precursor of BH4, significantly increased eNOS activity, whereas addition of vitamin C to cells treated with sepiapterin did not cause any further increase in eNOS activity. Our results suggest that the beneficial effect of vitamin C on endothelial function is best explained by increased intracellular BH4 content and subsequent enhancement of eNOS activity. This effect appears to be independent of the ability of vitamin C to scavenge superoxide anions.

Original languageEnglish (US)
Pages (from-to)333-338
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Issue number3
StatePublished - 2001


  • MnTBAP
  • Nitric oxide synthase
  • Peroxynitrite
  • Tetrahydrobiopterin
  • Vitamin C

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine


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