Glyceryl trinitrate but not spontaneous NO donors preserve myocardial function and cell integrity in ischemic rabbit hearts.

Langendorff-perfused rabbit hearts were subjected to 2 h of global, low-flow ischemia followed by 30 min of reperfusion. This resulted in a marked increase of left ventricular enddiastolic pressure and a loss in left ventricular creatine phosphokinase activity. NO formation was significantly reduced in early reperfusion. In the presence of superoxide dismutase (20 U/ml), NO release (oxyhemoglobin technique) was completely normalized, indicating inactivation of NO by superoxide radicals. Treatment with glyceryl trinitrate (GTN; 30 microM) prevented ischemia-induced myocardial tissue injury. SIN-1 (0.3 microM) was ineffective. These data demonstrate a protective effect of GTN but not SIN-1 in myocardial ischemia. It is concluded that the site of NO generation may play an important role in determining the biological activity of NO donating substances.