Article

Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury in L-NAME-induced hypertensive rats.

Department of Pharmacology, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima-city, Tokushima 770-8503, Japan.
American journal of physiology. Renal physiology (impact factor: 3.68). 09/2008; 295(5):F1457-62. DOI:10.1152/ajprenal.00621.2007 pp.F1457-62
Source: PubMed

ABSTRACT We have reported that pharmacological doses of oral nitrite increase circulating nitric oxide (NO) and exert hypotensive effects in Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. In this study, we examined the effect of a chronic dietary dose of nitrite on the hypertension and renal damage induced by chronic L-NAME administration in rats. The animals were administered tap water containing L-NAME (1 g/l) or L-NAME + nitrite (low dose: 0.1 mg/l, medium dose: 1 mg/l, high dose: 10 mg/l) for 8 wk. We evaluated blood NO levels as hemoglobin-NO adducts (iron-nitrosyl-hemoglobin), using an electron paramagnetic resonance method. Chronic administration of L-NAME for 8 wk induced hypertension and renal injury and reduced the blood iron-nitrosyl-hemoglobin level (control 38.8 +/- 8.9 vs. L-NAME 6.0 +/- 3.1 arbitrary units). Coadministration of a low dose of nitrite with L-NAME did not change the reduced iron-nitrosyl-hemoglobin signal and did not improve the L-NAME-induced renal injury. The blood iron-nitrosyl-hemoglobin signals of the medium dose and high dose of nitrite were significantly higher than that of L-NAME alone. Chronic administration of a medium dose of nitrite attenuated L-NAME-induced renal histological changes and proteinuria. A high dose of nitrite also attenuated L-NAME-induced renal injury. These findings suggest that dietary doses of nitrite that protect the kidney are associated with significant increase in iron-nitrosyl-hemoglobin levels. We conclude that dietary nitrite-derived NO generation may serve as a backup system when the nitric oxide synthase/L-arginine-dependent NO generation system is compromised.

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Keywords

8 wk induced hypertension
 
backup system
 
blood iron-nitrosyl-hemoglobin level
 
blood iron-nitrosyl-hemoglobin signals
 
Chronic administration
 
chronic dietary dose
 
chronic L-NAME administration
 
electron paramagnetic resonance method
 
hemoglobin-NO adducts
 
hypotensive effects
 
iron-nitrosyl-hemoglobin levels
 
L-NAME + nitrite
 
L-NAME)-induced hypertensive rats
 
L-NAME-induced renal injury
 
nitric oxide
 
nitric oxide synthase/L-arginine-dependent
 
nitrite attenuated L-NAME-induced renal histological changes
 
oral nitrite increase
 
reduced iron-nitrosyl-hemoglobin signal
 
renal damage induced