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 micromol/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.
Tomiyama
Hirofumi
H
Second Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan. tomiyama@tokyo-med.ac.jp
Watanabe
Gohki
G
Yoshida
Hideo
H
Doba
Nobutaka
N
Yamashina
Akira
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage*; D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage; D005260:Female; D005665:Furosemide / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D005665:Furosemide; D006152:Cyclic GMP; D001205:Ascorbic Acid