Update on Endogenous HNO Production: An Exploration of Unanswered Questions and Challenges

Abstract

This review consolidates the evidence supporting endogenousHNO generation through enzymatic and non-enzymatic pathways,emphasizing advancements in real-time HNO sensingwithin living systems. Azanone (nitroxyl, HNO) is the oneelectron-reduced congener of nitric oxide (NO*) and sharesvarious biological actions. HNO exhibits unique properties,including positive inotropic and lusitropic effects, along withresistance to scavenging by reactive oxygen species (ROS),particularly superoxide. Research on HNO has intensified overthe last two decades, focusing on its reactivity and the prospectof endogenous formation due to its potential significance. Thehigh reactivity of HNO arises from reactions with biologicallyrelevant species such as oxygen, NO*, and thiols, as well as selfdimerization.Detecting and quantifying HNO has posedchallenges, initially relying on nitrous oxide (N2O) detection, abyproduct of dimerization. Recent advancements, includingfluorescent probes and a specific electrochemical nanomolarlevelsensor, have facilitated direct detection, enhancing understandingof HNO reactivity and formation.