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Nitroxyl: A Novel Strategy to Circumvent Diabetes Associated Impairments in Nitric Oxide Signaling

Anida Velagic1,2,3, Chengxue Qin1,2,3, Owen L Woodman3

  • 1Heart Failure Pharmacology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Frontiers in Pharmacology
|June 9, 2020
PubMed

Insights

Diabetes causes cardiovascular issues due to impaired nitric oxide (NO•) signaling, termed NO• resistance. Nitroxyl (HNO) donors show promise in overcoming this resistance and treating heart complications in type 2 diabetes.

Area of Science:

  • Cardiovascular Medicine
  • Endocrinology
  • Pharmacology

Background:

  • Diabetes mellitus is linked to higher cardiovascular mortality.
  • Hyperglycemia-induced oxidative stress impairs nitric oxide (NO•) signaling, causing NO• resistance.
  • NO• resistance compromises cardiovascular function and reduces the effectiveness of NO•-based therapies.

Purpose of the Study:

  • To explore mechanisms linking hyperglycemia-induced oxidative stress to NO• resistance in diabetes.
  • To review the therapeutic potential of nitroxyl (HNO) donors in circumventing NO• resistance.
  • To assess HNO donors for treating cardiovascular complications in type 2 diabetes mellitus.

Main Methods:

  • Literature review of mechanisms of NO• resistance in diabetes.
  • Analysis of studies on agents that ameliorate or circumvent NO• resistance.
  • Evaluation of the properties and therapeutic potential of HNO donors.

Main Results:

  • Hyperglycemia-driven oxidative stress is a key factor in NO• resistance.
  • Existing therapies have limitations in addressing NO• resistance.
  • HNO donors possess vasoprotective and cardiac-enhancing properties, with preserved efficacy under oxidative stress.

Conclusions:

  • HNO donors represent a novel therapeutic strategy to overcome NO• resistance in diabetes.
  • HNO donors may offer a viable treatment for cardiovascular complications associated with type 2 diabetes.
  • Further research into HNO donors is warranted for managing diabetic cardiovascular emergencies.
Keywords:
HNOcardiovascular diseasediabetesnitric oxidenitric oxide resistancenitroxyltype 2 diabetes

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