BACKGROUND: Essential hypertension is characterized by both increased oxidative stress and sympathetic traffic. Experimental studies have shown that reactive oxygen species can modulate autonomic activity. OBJECTIVE: The aim of this study was to determine whether acute administration of the antioxidant vitamin C modifies sympathetic nerve activity in essential hypertension. DESIGN: Thirty-two untreated patients with essential hypertension and 20 normotensive subjects received vitamin C (3 g intravenously in 5 min) or vehicle. Heart rate, noninvasive beat-to-beat blood pressure, and muscle sympathetic nerve activity (microneurography) were monitored at baseline and up to 20 min after the infusion. Spectral analysis of RR interval variability and spontaneous baroreflex sensitivity were also computed. RESULTS: Vitamin C infusion significantly lowered blood pressure in hypertensive patients but not in normotensive subjects (maximal changes in systolic blood pressure: -4.9 +/- 10.1 compared with -0.7 +/- 4.0 mm Hg, respectively; P < 0.05). Moreover, muscle sympathetic nerve activity was significantly reduced after vitamin C infusion in hypertensive patients (from 53.3 +/- 12.2 to 47.4 +/- 11.5 bursts/100 heart beats; P < 0.01) but not in healthy subjects (from 42.0 +/- 10.1 to 42.7 +/- 11.8 bursts/100 heart beats; NS). On the contrary, in 16 hypertensive patients, sodium nitroprusside in equidepressor doses induced a significant increase in muscle sympathetic nerve activity compared with vitamin C (+10.0 +/- 6.9 bursts/100 heart beats). Sympathovagal balance and spontaneous baroreflex sensitivity were restored during vitamin C infusion in hypertensive subjects. CONCLUSION: These results indicate that acute administration of vitamin C is able to reduce cardiovascular adrenergic drive in hypertensive patients, which suggests that oxidative stress is involved in the regulation of sympathetic activity in essential hypertension.