Nitric oxide and peroxynitrite in postischemic myocardium

Area of Science:

• Cardiovascular Research
• Biochemistry
• Pathophysiology

Background:

• Alterations in nitric oxide (NO) production are implicated in myocardial injury following ischemia and reperfusion.
• The role of peroxynitrite (ONOO-), a cytotoxic oxidant formed from NO and superoxide, in postischemic injury remains controversial.

Purpose of the Study:

• To investigate the formation and role of NO and ONOO- during early reperfusion in the postischemic heart.
• To determine the contribution of ONOO- to myocardial injury and contractile dysfunction.

Main Methods:

• Electron paramagnetic resonance (EPR) spin trapping with Fe-MGD to detect NO formation.
• Chemiluminescence with luminol to detect ONOO- formation.
• Measurement of cardiac contractile function and immunohistology for nitrotyrosine.

Main Results:

• Prominent NO adduct signals and increased ONOO- formation were observed within the first 2 minutes of reperfusion.
• NO and ONOO- formation during reperfusion were blocked by nitric oxide synthase inhibitors.
• Treatment with NOS inhibitors or superoxide dismutase significantly improved recovery of contractile function.
• Nitrotyrosine, an ONOO- mediated product, was detected in postischemic myocardium.

Conclusions:

• Increased NO production during early reperfusion contributes to myocardial injury via ONOO- formation.
• ONOO- mediates protein nitration and impairs cardiac function after ischemia-reperfusion.
• Targeting NO or superoxide during reperfusion may protect the myocardium from injury.