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

Authors:
  • KYKunihisa Yamaguchi
    Kunihisa Yamaguchi
  • HOHideki Ohnishi
    Hideki Ohnishi
  • YMYuki Motobayashi
    Yuki Motobayashi
  • KIKeisuke Ishizawa
    Keisuke Ishizawa
  • YIYuki Izawa
    Yuki Izawa
  • KKKazuyoshi Kawazoe
    Kazuyoshi Kawazoe
  • SKShuji Kondo
    Shuji Kondo
  • SKShoji Kagami
    Shoji Kagami
  • STShuhei Tomita
    Shuhei Tomita
  • KTKoichiro Tsuchiya
    Koichiro Tsuchiya
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Abstract
We have reported that pharmacological doses of oral nitrite increase circulating nitric oxide (NO) and exert hypotensive effects in Nω-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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