Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning

Area of Science:

• Cardiovascular Physiology
• Biochemistry
• Pharmacology

Background:

• Nitric oxide (NO) donors replicate early ischemic preconditioning (IPC) effects.
• The role of nitroxyl (HNO/NO(-)), NO's reduction product, in ischemia/reperfusion (I/R) injury remains unclear.

Purpose of the Study:

• To investigate the cardioprotective potential of nitroxyl (HNO/NO(-)) against I/R injury.
• To compare the effects of HNO/NO(-) with NO donors and IPC in isolated perfused rat hearts.

Main Methods:

• Hearts underwent global ischemia (30 min) and reperfusion (30-120 min) after intracoronary perfusion.
• Interventions included Angeli's salt (AS) for HNO/NO(-) generation, diethylamine/NO (DEA/NO) as an NO donor, vehicle, or buffer.
• Ischemic preconditioning (IPC) was induced prior to I/R. Myocardial contractility, lactate dehydrogenase (LDH) release, and infarct size were assessed.

Main Results:

• Pre-exposure to AS significantly improved postischemic contractility, reduced LDH release, and decreased infarct size, similar to IPC.
• DEA/NO showed less effectiveness in limiting necrosis compared to AS and IPC.
• Co-infusion of AS with a nitroxyl scavenger (N-acetyl-L-cysteine) abolished the protective effects of AS.

Conclusions:

• HNO/NO(-) provides significant myocardial protection against I/R injury, comparable to IPC and superior to NO.
• These findings suggest that reactive nitrogen oxide species are sufficient to trigger cardioprotection.
• Mechanisms may involve species-dependent, pro-oxidative, and/or nitrosative stress pathways.