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Stimulation of µ- and delta-Opiate Receptors and Tolerance of Isolated Heart to Oxidative Stress: the Role of NO-Synthase

T. Yu. Rebrova1, L. N. Maslov1*, A. Yu. Lishmanov1, and S. V. Tam2

1Laboratory of Experimental Cardiology, Research Institute of Cardiology, Siberian Branch of the Russian Academy of Medical Sciences, ul. Kievskaya 111, Tomsk, 634050 Russia; E-mail: nuclear@cardio.tsu.ru

2NitroMed Company, Bedford, Massachusetts, USA

* To whom correspondence should be addressed.

Received September 28, 2000; Revision received December 19, 2000
Preliminary intravenous injection of delta-opiate receptor (OR) agonists DSLET (0.1 mg/kg) or DTLET (0.1 mg/kg) increased tolerance of isolated perfused myocardium to damage by oxidative stress simulated in vivo with FeSO4 + ascorbic acid. This manifested itself by a decreased level of creatine phosphokinase (CPK) in the perfusate flowing out of the heart during the oxidative exposure. The preliminary systemic injection of µ-agonists DAMGO (0.1 mg/kg) or DALDA (0.1 mg/kg) failed to affect the release of CPK from the myocardium. The cardioprotective effect of the delta-agonist DSLET was completely abolished by preliminary intravenous injection of the delta-OR antagonist ICI 174,864 (2.5 mg/kg). The intravenous injection of the NO-synthase inhibitor L-NAME (50 mg/kg) also completely abolished the cardioprotective effect of delta-OR stimulation. The preliminary injection of DSLET but not of DAMGO prevented an increase in the level of diene conjugates and a decrease in the activity of superoxide dismutase (SOD) in the isolated myocardium tissue. Thus, the in vivo stimulation of delta-OR increased the tolerance of the heart to oxidative stress through activation of NO-synthase and SOD.
KEY WORDS: opiate peptides, lipid peroxidation, superoxide dismutase, NO-synthase, oxidative stress