Enhanced nitric oxide production during mg-deficiency and its role
in mediating red cell glutatione loss.
Mak, I. Tong, Andrei M. Komarov, Tammy L. Wagner, Richard E. Stafford,
Benjamin F. Dichens, William B. Weglicki.
Departments of Medicine & Physiology, Division of Experimental
Medicine, George Washington University Medical Center, Washington DC,
20037
APStracts 3:0024C, 1996.
The effect of dietary Mg-deficiency on nitric oxide (NO) production
and its role in mediating oxidative depletion of red cell glutathione
in the rat were investigated. Male SD-rats were placed on Mg
-deficient or Mg-sufficient diets up to 3 weeks. Plasma
nitrate/nitrite levels, determined by the E. coli reductase/Griess
reagent procedures, increased 1.7-fold during the first week and
increased 2-2.4 fold during the second and third weeks on the Mg
-deficient diet. In association, substantial losses (50%) of red cell
glutathione occurred during the second and third weeks.
Administration of the NO-synthesis inhibitor, NG-nitro-L-arginine
methyl ester (L-NAME), in the drinking water (0.5 mg/ml) effectively
blunted the increases in plasma nitrate/nitrite during Mg-deficiency.
Concomitantly, losses of the red cell glutathione exhibited by Mg
-deficient rats were significantly attenuated. The packed red cells,
obtained from the Mg-deficient, but not from the Mg-sufficient,
animals displayed a prominent nitrosyl-hemoglobin (HbNO) signal
detected by ESR spectroscopy; the signals of the samples from the L
-NAME treated Mg-deficient rats were greatly reduced. With isolated
red blood cells, losses of the glutathione could be induced directly
by peroxynitrite, or 3-morpholinosydnonimine (SIN-1) which generates
NO + .O2-, but not by NO (from Na-nitroprusside) alone, in a
concentration-dependent manner. The results clearly indicate that NO
overproduction occurs and participates in red cell gluthione loss
during Mg-deficiency. Since neutrophil activation also occurs, we
suggest that NO might interact with superoxide anions to form
peroxynitrite which then directly oxidizes red cell glutathione.
Received 27 September 1995; accepted in final form 11 January
1996.
APS Manuscript Number C592-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96