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

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 mu g.100 mL(-1). min(-1)) or sodium nitroprusside (1, 2, and 4 mu g/100 mt 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 mu g/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 mu g/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.