PMID- 12514674
OWN - NLM
STAT- MEDLINE
DCOM- 20030306
LR  - 20131121
IS  - 1097-6744 (Electronic)
IS  - 0002-8703 (Linking)
VI  - 145
IP  - 1
DP  - 2003 Jan
TI  - Reduction of oxidative stress augments natriuretic effect of furosemide in 
      moderate heart failure.
PG  - E2
AB  - 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.
FAU - Tomiyama, Hirofumi
AU  - Tomiyama H
AD  - Second Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan. 
      tomiyama@tokyo-med.ac.jp
FAU - Watanabe, Gohki
AU  - Watanabe G
FAU - Yoshida, Hideo
AU  - Yoshida H
FAU - Doba, Nobutaka
AU  - Doba N
FAU - Yamashina, Akira
AU  - Yamashina A
LA  - eng
PT  - Clinical Trial
PT  - Controlled Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Am Heart J
JT  - American heart journal
JID - 0370465
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 69PN84IO1A (Enalapril)
RN  - 7LXU5N7ZO5 (Furosemide)
RN  - H2D2X058MU (Cyclic GMP)
RN  - PQ6CK8PD0R (Ascorbic Acid)
SB  - IM
MH  - Angiotensin-Converting Enzyme Inhibitors/administration & dosage
MH  - Ascorbic Acid/*administration & dosage
MH  - Cross-Over Studies
MH  - Cyclic GMP/blood/urine
MH  - Drug Therapy, Combination
MH  - Enalapril/administration & dosage
MH  - Female
MH  - Furosemide/*therapeutic use
MH  - Heart Failure/*drug therapy/*physiopathology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Oxidative Stress/*drug effects
EDAT- 2003/01/07 04:00
MHDA- 2003/03/07 04:00
CRDT- 2003/01/07 04:00
PHST- 2003/01/07 04:00 [pubmed]
PHST- 2003/03/07 04:00 [medline]
PHST- 2003/01/07 04:00 [entrez]
AID - S0002870302947514 [pii]
AID - 10.1067/mhj.2003.42 [doi]
PST - ppublish
SO  - Am Heart J. 2003 Jan;145(1):E2. doi: 10.1067/mhj.2003.42.