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

Am J Physiol Renal Physiol. 2008 Nov;295(5):F1457-62. doi: 10.1152/ajprenal.00621.2007. Epub 2008 Aug 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Diet
  • Glycated Hemoglobin
  • Hypertension / chemically induced
  • Hypertension / physiopathology*
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney Diseases / blood
  • Kidney Diseases / chemically induced
  • Kidney Diseases / prevention & control*
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / pathology
  • Male
  • NG-Nitroarginine Methyl Ester
  • Nitrates / administration & dosage
  • Nitrates / pharmacology*
  • Nitrates / therapeutic use
  • Nitric Oxide / blood*
  • Proteinuria / blood
  • Proteinuria / drug therapy
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Glycated Hemoglobin A
  • Nitrates
  • hemoglobin A, glycosylated-nitric oxide complex
  • Nitric Oxide
  • sodium nitrate
  • NG-Nitroarginine Methyl Ester