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

摘要: Diabetes is associated with an increased mortality risk due to cardiovascular complications. Hyperglycemia-induced oxidative stress underlies these complications, leading impairment in endogenous nitric oxide (NO•) generation, together reductions NO• bioavailability and responsiveness the vasculature, platelets myocardium. The latter of NO•, termed resistance, compromises ability traditional NO•-based therapeutics improve hemodynamic status during diabetes-associated emergencies, such as acute myocardial infarction. Whilst a number agents can ameliorate (e.g. angiotensin converting enzyme [ACE] inhibitors, perhexiline, statins insulin) or circumvent nitrite sGC activators) nitroxyl (HNO) donors offer novel opportunity resistance diabetes. With suite vasoprotective properties enhance cardiac inotropic lusitropic responses, coupled preserved efficacy setting stress, HNO have intact therapeutic potential face diminished signaling. This review explores major mechanisms by which hyperglycemia-induced drives this treat complications type 2 diabetes mellitus.