Nitric oxide synthase inhibitors decrease coronary sinus-free radical concentration and ameliorate myocardial...

Area of Science:

• Cardiovascular Research
• Free Radical Biology
• Ischemia-Reperfusion Injury

Background:

• Ischemia-reperfusion sequences generate cardiotoxic free radicals.
• Nitric oxide (NO) can react with superoxide to form peroxynitrite, increasing free radical formation.
• Inhibiting NO production may offer cardioprotection by reducing oxidative stress.

Purpose of the Study:

• To investigate the impact of NG-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor, on free radical generation.
• To assess the effect of L-NNA on myocardial contractility following ischemia-reperfusion.
• To determine if inhibiting NO production is cardioprotective in an ischemia-reperfusion model.

Main Methods:

• Studied 32 dogs undergoing 20-minute coronary occlusion-reperfusion.
• Measured coronary sinus ascorbate free radical (Asc*-) concentration using electron paramagnetic resonance.
• Administered L-NNA intravenously during occlusion-reperfusion; control dogs received saline. Assessed myocardial nitrotyrosine presence via immunohistochemistry.

Main Results:

• L-NNA significantly reduced the rise in Asc*- concentration during reperfusion compared to controls (25% vs. 50% increase).
• L-NNA preserved left ventricular fractional area shortening (FAS) during reperfusion (no significant change from baseline), unlike controls (significant decline).
• Nitrotyrosine, a marker of peroxynitrite formation, was markedly reduced in L-NNA treated dogs.

Conclusions:

• Inhibition of nitric oxide synthase with L-NNA decreases coronary sinus free radical levels.
• L-NNA treatment ameliorates myocardial stunning following ischemia-reperfusion.
• These findings support the hypothesis that reducing NO production can be cardioprotective against ischemia-reperfusion injury.