title: Reduction of oxidative stress augments natriuretic effect of furosemide in moderate heart failure.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan. tomiyama@tokyo-med.ac.jp
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tomiyama
authors.forename: Gohki
authors.initials: G
authors.lastname: Watanabe
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshida
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Doba
authors.forename: Akira
authors.initials: A
authors.lastname: Yamashina
mesh_terms: 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*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D005665:Furosemide; D006152:Cyclic GMP; D001205:Ascorbic Acid