Reduction of oxidative stress augments natriuretic effect of furosemide in moderate heart failure

Background The significance of antioxidant therapy in heart failure has not been fully examined. This study evaluated whether vitamin C has beneficial effects on renal function or augments the renal effects of furosemide in patients with heart failure.Methods There were 2 protocols. In protocol 1, plasma level of thiobarbituric acid-reactive substances (TBARS) and renal function were assessed before and after intravenous infusion of vitamin C or placebo in 8 patients with moderate congestive heart failure (CHF) treated with enalapril. In protocol 2, a randomized crossover study was performed in patients with moderate CHF treated with either an ACE inhibitor (enalapril) (n = 10) or an angiotensin II receptor antagonist (losartan) (n = 9) and in asymptomatic patients with impaired left ventricular function treated with enalapril (n = 8). TBARS and renal function were assessed before and after intravenous infusion of furosemide alone, coinfusion of furosemide with placebo and vitamin C, or coinfusion of furosemide with vitamin C and a kallikrein inhibitor (nafamostat mesilate).Results In protocol 1, although vitamin C reduced TBARS, it did not affect renal function. In protocol 2, TBARS was higher in patients with moderate CHF than in asymptomatic patients. Vitamin C augmented natriuretic effect of furosemide (from 179 ± 98 to 192 ± 104 μmol/min, P < .01) only in patients with moderate CHF treated with enalapril but not in the other 2 groups. Nafamostat mesilate prevented this augmentation.Conclusions In patients with CHF treated with enalapril, counteraction of the increased oxidative stress by vitamin C may contribute to the augmented natriuretic effect of furosemide through the renal kinin-nitric oxide pathway. (Am Heart J 2003;145:e2.)