(Circulation. 1999;100:2260.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Classic Preconditioning Decreases the Harmful Accumulation of Nitric Oxide During Ischemia and Reperfusion in Rat Hearts
From the Departments of Biochemistry (C.C., Z.S., A.T., P.F.) and Pharmaceutical Chemistry (F.F.), Albert Szent-Györgyi University, and the Department of Biophysics (T.P.), Biological Research Center, Szeged, Hungary; the Institute of Molecular Pharmacology (C.C., I.E.B.), Berlin, Germany; and the Departments of Pediatrics and Pharmacology, Cardiovascular Research Group (R.S., P.F.), University of Alberta, Edmonton, Canada.
Correspondence to Peter Ferdinandy, MD, PhD, Cardiovascular Research Group, Department of Biochemistry, Albert Szent-Györgyi University Medical School, PO Box 427, Szeged, H-6701, Hungary. E-mail peter{at}biochem.szote.u-szeged.hu
Background—The role of NO in the mechanism of preconditioning is not understood. Therefore, we studied the effect of preconditioning and subsequent ischemia/reperfusion on myocardial NO content in the presence of an NO synthase (NOS) inhibitor.
Methods and Results—Isolated working rat hearts were subjected to preconditioning protocols of 3 intermittent periods of rapid pacing or no-flow ischemia of 5 minutes’ duration each followed by a test 30 minutes of global no-flow ischemia and 15 minutes of reperfusion. Test ischemia/reperfusion resulted in a deterioration of myocardial function and a considerable increase in cardiac NO content as assessed by electron spin resonance. Preconditioning improved postischemic myocardial function and markedly decreased test ischemia/reperfusion-induced NO accumulation. In the presence of 4.6 µmol/L NG-nitro-L-arginine (LNA), basal cardiac NO content decreased significantly, although test ischemia/reperfusion-induced functional deterioration and NO accumulation were not affected in nonpreconditioned hearts. However, the protective effects of preconditioning on both test ischemia/reperfusion-induced functional depression and NO accumulation were abolished. When 4.6 µmol/L LNA was administered after preconditioning, it failed to block the effect of preconditioning. In the presence of 46 µmol/L LNA, ischemia/reperfusion-induced NO accumulation was significantly decreased and postischemic myocardial function was improved in nonpreconditioned hearts.
Conclusions—Our results show that (1) although NO synthesis by the heart is necessary to trigger classic preconditioning, preconditioning in turn attenuates the accumulation of NO during ischemia/reperfusion, and (2) blockade of ischemia/reperfusion-induced accumulation of cardiac NO by preconditioning or by an appropriate concentration of NOS inhibitor alleviates ischemia/reperfusion injury as demonstrated by enhanced postischemic function.
Key Words: nitric oxide • preconditioning • ischemia • reperfusion • electron spin resonance
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