Vitamin C promotes the release of nitric oxide (NO) from nitrosothiols and in isolated pre-contracted rabbit aortic rings potentiates relaxation to nitroprusside (de Saram et al, 2002). Previous studies in the human forearm have shown no effect of vitamin C on vasodilator responses to nitroprusside (Ting et al, 1997). Such studies have, however, been performed using high concentrations of vitamin C which may inactivate NO. We re-examined effects of vitamin C using doses calculated to produce a 2 – 10 fold increase in concentrations within forearm vasculature. Forearm blood flow studies were performed on healthy volunteers (average age 34 years, n=6). The study was approved by the local research ethics committee and all subjects gave written informed consent. The brachial artery was cannulated with a 27 gauge needle and drugs or saline infused at 1 ml/min. Forearm blood flow was measured using strain gauge plethysmography. Following 15 min infusion of saline to establish basal flow, subjects received nitroprusside (1 and 3 µg/min, each dose for 5 min) alone and during co-infusion of vitamin C (1 and 5 µg/min). Saline alone was infused for 10 min after nitroprusside to allow blood flow to return to baseline and vitamin C infused alone for 5 min before co-infusion with nitroprusside. In a control study performed on a separate occasion, 6 subjects received an infusion of nitroprusside (1 and 3 µg/min, each dose for 5 min) followed after 15 min by a second identical infusion of nitroprusside. Forearm blood flow increased from 2.7 ±1.0 to 5.1 ±1.1 and 7.3 ±1.3 during infusion of nitroprusside 1 and 3 mg/min respectively (P<0.01). Responses to a second identical infusion were similar. Vitamin C alone had no significant effect on blood flow but when co-infused with nitroprusside increased forearm blood flow. For the higher dose of nitroprusside, vitamin C increased blood flow from 7.3 ±1.3 to 9.7 ±1.2 and 10.1 ±1.1 for vitamin C 1 and 5 mg/min respectively (each P<0.05). These data suggest that increases in plasma concentrations of vitamin C may potentiate the release of NO from nitroprusside and possibly other NO donors such as nitrosothiols. This could contribute to the vasodilator actions of Vitamin C in conditions where the production of endogenous nitrosothiols is increased or during nitrate therapy. de Saram et al (2002) Br. J. Pharmacol.135, 1044-1050. |