Nitroxyl: a novel strategy to circumvent diabetes associated impairments in nitric oxide signaling

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dc.contributor.authorVelagic, A.
dc.contributor.authorQin, C.
dc.contributor.authorWoodman, O.L.
dc.contributor.authorHorowitz, J.D.
dc.contributor.authorRitchie, R.H.
dc.contributor.authorKemp-Harper, B.K.
dc.date.issued2020
dc.description.abstractDiabetes is associated with an increased mortality risk due to cardiovascular complications. Hyperglycemia-induced oxidative stress underlies these complications, leading to an impairment in endogenous nitric oxide (NO•) generation, together with reductions in NO• bioavailability and NO• responsiveness in the vasculature, platelets and myocardium. The latter impairment of responsiveness to NO•, termed NO• resistance, compromises the ability of traditional NO•-based therapeutics to improve hemodynamic status during diabetes-associated cardiovascular emergencies, such as acute myocardial infarction. Whilst a number of agents can ameliorate (e.g. angiotensin converting enzyme [ACE] inhibitors, perhexiline, statins and insulin) or circumvent (e.g. nitrite and sGC activators) NO• resistance, nitroxyl (HNO) donors offer a novel opportunity to circumvent NO• resistance in diabetes. With a suite of vasoprotective properties and an ability to enhance cardiac inotropic and lusitropic responses, coupled with preserved efficacy in the setting of oxidative stress, HNO donors have intact therapeutic potential in the face of diminished NO• signaling. This review explores the major mechanisms by which hyperglycemia-induced oxidative stress drives NO• resistance, and the therapeutic potential of HNO donors to circumvent this to treat cardiovascular complications in type 2 diabetes mellitus.
dc.description.statementofresponsibilityAnida Velagic, Chengxue Qin, Owen L. Woodman, John D. Horowitz, Rebecca H. Ritchie, and Barbara K. Kemp-Harper
dc.identifier.citationFrontiers in Pharmacology, 2020; 11:727-1-727-18
dc.identifier.doi10.3389/fphar.2020.00727
dc.identifier.issn1663-9812
dc.identifier.issn1663-9812
dc.identifier.orcidHorowitz, J.D. [0000-0001-6883-0703]
dc.identifier.urihttp://hdl.handle.net/2440/126900
dc.language.isoen
dc.publisherFrontiers Media SA
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1120859
dc.rightsCopyright © 2020 Velagic, Qin, Woodman, Horowitz, Ritchie and Kemp-Harper. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.source.urihttps://doi.org/10.3389/fphar.2020.00727
dc.subjectNitric oxide; diabetes; type 2 diabetes; cardiovascular disease; nitroxyl; HNO; nitric oxide resistance
dc.titleNitroxyl: a novel strategy to circumvent diabetes associated impairments in nitric oxide signaling
dc.typeJournal article
pubs.publication-statusPublished

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