D-Ala, D-Leu Enkephalin delays ouabain-induced arrhythmia in isolated rat atria

Opioid receptor stimulation inhibits voltage-gated calcium channels causing the opening of potassium channels thereby inducing membrane hyperpolarization. Also, it has negative inotropic effect on the heart. Ouabain -a cardiac glycoside- induces cell membrane depolarization that leads to ouabain-induced arrhythmia. This study was aimed at exploring antiarrhythmic activity of D-Ala, D-Leu Enkephalin (DADLE) -a specific delta opioid receptor agonist- on ouabain-induced arrhythmia in rat atria. Eighteen male rats including the control and DADLE-incubated (100 nM or 1 µM) ouabain-stimulated groups were used. After induction of anesthesia, the atria were isolated and spontaneously beating rate, chronotropic responsiveness, and onset of arrhythmia and asystole were assessed following incubation by DADLE and stimulation by ouabain using standard organ bath. One-way analysis of variance (ANOVA) was used for the evaluation of the effect of two different doses of DADLE. Dunnett s multiple comparison test was then performed for multiple comparisons. P-values less than 0.05 were considered as statistically significant. DADLE induced significant delay in onset of arrhythmia compared to control group (P≤0.01). Although it did not delay the onset of asystole, but was able to significantly increase the heart rate in isolated rat atria (P≤0.01). Furthermore, it suppressed the positive chronotropic effect of ouabain (P≤0.05). It is concluded that DADLE can effectively alleviate the ouabain-induced arrhythmia in rats. Such results might be attributed to hyperpolarization of cell membrane or reduction of ouabain toxicity in myocardium.