Oral nitrite therapy improves vascular function in diabetic mice

Diab Vasc Dis Res. 2015 May;12(3):221-4. doi: 10.1177/1479164114565628. Epub 2015 Feb 12.

Abstract

Aim: We tested the hypothesis that short-term oral sodium nitrite supplementation would improve vascular dysfunction in obese, diabetic mice.

Methods and results: Vascular function was determined in control mice and in db/db mice receiving drinking water with or without sodium nitrite (50 mg/L) for 5 weeks. Nitrite supplementation increased plasma nitrite concentrations in db/db mice (0.19±0.02 µM vs 0.80±0.26 µM; p < 0.05). Db/db mice had lower endothelium-dependent dilation (EDD) in response to increasing doses of acetylcholine versus heterozygous control mice (71.2% ± 14.3% vs 93% ± 7.0%; p < 0.05), and sodium nitrite supplementation restored endothelium-dependent dilation to control levels (92.9% ± 2.3% vs 93% ± 7.0%; p < 0.05). The improvement in endothelial function was accompanied by a reduction in intrinsic stiffness, but not by alterations in plasma or vascular markers of inflammation.

Conclusion: These data suggest that sodium nitrite may be a novel therapy for treating diabetes-related vascular dysfunction; however, the mechanisms of improvement are unknown.

Keywords: Endothelial function; diabetes; nitrite.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Animals
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / diagnosis
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / genetics
  • Diabetic Angiopathies / physiopathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Heterozygote
  • Homozygote
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Point Mutation
  • Receptors, Leptin / genetics
  • Sodium Nitrite / administration & dosage*
  • Sodium Nitrite / blood
  • Vascular Stiffness / drug effects
  • Vasodilation / drug effects*
  • Vasodilator Agents / administration & dosage*
  • Vasodilator Agents / blood

Substances

  • Receptors, Leptin
  • Vasodilator Agents
  • leptin receptor, mouse
  • Sodium Nitrite