Nitric oxide (•NO) is a central regulator of plant development and stress responses, but recent evidence shows that reactive nitrogen signaling involves more than •NO alone. Nitroxyl (HNO), the one-electron-reduced and protonated form of •NO, has emerged as a distinct signaling molecule in plants with unique chemical and functional properties. Unlike •NO, HNO is a non-radical, thiophilic species that acts as a selective redox modulator rather than a freely diffusible messenger. Improved detection methods have confirmed endogenous HNO formation in plant cells, with basal nanomolar concentrations under optimal conditions and reversible changes during key developmental stages and stress responses, such as senescence and hypoxia. HNO production and stability are closely regulated by intracellular redox status and interconvert dynamically with •NO through non-enzymatic reactions involving cellular reductants such as ascorbate, hydrogen sulfide, and low-molecular-weight thiols. This interplay establishes the •NO/HNO balance as a redox-sensitive signaling switch, increasing the informational capacity of reactive nitrogen networks. Functional and transcriptomic studies indicate that HNO participates in hormone signaling, especially in ethylene-mediated pathways, and supports plant adaptation to redox-related stresses. This review summarizes current knowledge of HNO chemistry, regulation, detection, and function in plants, and identifies key open questions. Including HNO in plant signaling frameworks provides a more nuanced and comprehensive view of redox-regulated plant physiology.
BACKGROUND:Inhaled nitric oxide (iNO) is widely used as a pulmonary vasodilator to treat infants with pulmonary hypertension (PHN). Hypoxia (Hx) and acidosis increase pulmonary vascular resistance and contribute to PHN. Perinatal asphyxia and resultant hypoxic-ischemic encephalopathy (HIE) remain major causes of neonatal death and neurological impairment, and the impact of iNO on neurodevelopmental outcomes after HIE is unclear. Although hypothermia is the standard neuroprotective therapy for HIE, many infants still do not survive or continue to experience neurological impairments despite treatment. We investigated whether iNO improves survival and reduces brain injury after Hx in a neonatal piglet model. METHODS:Anesthetized, instrumented piglets (3-5 days old) were exposed to normoxic or hypoxic conditions for 1 h. After Hx, animals were either euthanized or reoxygenated with or without iNO (20 ppm) initiated within 10 min and continued for 4 h, while maintained at normothermia or hypothermia. Piglets were then euthanized for cortical analysis of ATP, lactate, HMGB1 (a marker of cell death), and water content using enzymatic assays, Western blotting, and drying methods, and results were compared with non-reoxygenated hypoxic animals, normoxic sham controls, and non-instrumented piglets. RESULTS:Treatment with iNO (20 ppm) starting 10 min after Hx improved survival. However, among surviving hypoxic piglets, iNO was associated with greater ATP depletion, increased cerebral lactic acidosis, more severe cerebral edema, and elevated HMGB1 expression compared with untreated hypoxic controls. Concurrent hypothermia did not mitigate these adverse effects. CONCLUSION:iNO improved survival after Hx but was associated with worsened biochemical and cellular markers of brain injury, despite hypothermia.
