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.
Woditsch
I
I
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, FRG.
Schrör
K
K
D000818:Animals; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology*; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology*
D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D005996:Nitroglycerin