Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension

Circulation. 1998 Jun 9;97(22):2222-9. doi: 10.1161/01.cir.97.22.2222.


Background: Essential hypertension is associated with impaired endothelium-dependent vasodilation. Inactivation of endothelium-derived nitric oxide by oxygen free radicals participates in endothelial dysfunction in experimental hypertension. To test this hypothesis in humans, we evaluated the effect of antioxidant vitamin C on endothelium-dependent responses in essential hypertensive patients.

Methods and results: In 14 healthy subjects (47.1+/-4.8 years; blood pressure, 120.6+/-4.5/80.9+/-3.5 mm Hg) and 14 essential hypertensive patients (47.3+/-5.1 years; blood pressure, 153.9+/-7.1/102.3+/-4.1 mm Hg), we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg x 100 mL(-1) x min(-1)) or sodium nitroprusside (1, 2, and 4 microg/100 mL forearm tissue per minute), an endothelium-dependent and -independent vasodilator, respectively, in basal conditions and during infusion of intrabrachial vitamin C (2.4 mg/100 mL forearm tissue per minute). In hypertensive patients but not in control subjects, vitamin C increased (P<0.01) the impaired vasodilation to acetylcholine, whereas the response to sodium nitroprusside was unaffected. Moreover, in another 14 hypertensive patients (47.1+/-5.2 years; blood pressure, 155.2+/-6.9/103.7+/-4.5 mm Hg), the facilitating effect of vitamin C on vasodilation to acetylcholine was reversed by N(G)-monomethyl-L-arginine (100 microg/100 mL forearm tissue per minute), a nitric oxide synthase inhibitor, suggesting that in essential hypertension superoxide anions impair endothelium-dependent vasodilation by nitric oxide breakdown. Finally, because in adjunctive 7 hypertensive patients (47.8+/-6.1 years; blood pressure, 155.3+/-6.8/103.5+/-4.3 mm Hg), indomethacin (50 microg/100 mL forearm tissue per minute), a cyclooxygenase inhibitor, prevented the potentiating effect of vitamin C on vasodilation to acetylcholine, it is possible that in essential hypertension a main source of superoxide anions could be the cyclooxygenase pathway.

Conclusions: In essential hypertensive patients, impaired endothelial vasodilation can be improved by the antioxidant vitamin C, an effect that can be reversed by the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine. These findings support the hypothesis that nitric oxide inactivation by oxygen free radicals contributes to endothelial dysfunction in essential hypertension.

Publication types

  • Clinical Trial

MeSH terms

  • Acetylcholine / pharmacology
  • Adult
  • Antioxidants / pharmacology*
  • Ascorbic Acid / pharmacology*
  • Cyclooxygenase Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / physiopathology*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Hypertension / physiopathology*
  • Indomethacin / pharmacology
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism*
  • Vasodilation / drug effects*
  • omega-N-Methylarginine / pharmacology


  • Antioxidants
  • Cyclooxygenase Inhibitors
  • Enzyme Inhibitors
  • omega-N-Methylarginine
  • Nitric Oxide
  • Acetylcholine
  • Ascorbic Acid
  • Indomethacin