Role of nitric oxide and oxidative stress in baroreceptor dysfunction in patients with chronic heart failure

Abnormalities of autonomic control of the cardiovascular system are seen in chronic heart failure (CHF) and confer a poor prognosis. Nitric oxide appears to be important in the regulation of baroreflex control in health and in disease states. The antioxidant vitamin C increases nitric oxide bioavailability in CHF. We evaluated the effects of vitamin C on baroreceptor sensitivity (BRS) by sequence analysis in 100 CHF patients and 44 control subjects. Groups of 55 CHF patients and 22 controls were randomly allocated to receive a single intravenous injection of vitamin C (2 g) or placebo. In addition, 45 CHF patients were randomly allocated to receive a 4-week course of oral vitamin C (4 g/day) or placebo. An age-related reference range for BRS was developed in 22 healthy controls matched for age and gender to the CHF group. BRS was significantly impaired in the CHF group compared with age-matched older controls and young controls (6.9 +/- 3.1, 12.5 +/- 4.9 and 21.7 +/- 9.1 mmHg/ms respectively; P <0.001 between groups). Intravenous vitamin C acutely improved BRS in CHF patients by 24% (by 1.8 +/- 4.1 mmHg/ms; P <0.05), but not in controls. There was no improvement in BRS in CHF patients given chronic oral vitamin C. Thus acute intravenous, but not chronic oral, vitamin C improved BRS in CHF patients. There was no effect of intravenous vitamin C in healthy subjects, suggesting that the mechanism was either by free radical scavenging or due to central effects.