Abstract
Inotropic actions of the endogenous enkephalins, leucine enkephalin [( Leu] enkephalin) and methionine enkephalin [( Met] enkephalin), and derivatives, [D-Ala2-methionine] enkephalinamide (DAMEA) and [D Ala2-leucine]enkephalinamide (DALEA) were tested, alone or in combination with noradrenaline (NA), (+/-)-isoprenaline or carbachol, on electrically-stimulated atria excised from Sprague-Dawley, fatty, Zucker (fa/fa) and lean, hooded heterozygous (Fa/fa) rats. [Met] enkephalin, [Leu] enkephalin, DAMEA and DALEA (4 X 10(-7)M to 4 X 10(-4)M) caused no significant changes in atrial tension in any group compared to pre-injection control values or those following the infusion of Krebs-Henseleit control solution. NA and isoprenaline (10(-7) to 10(-6)M) caused significant, dose-related increases in atrial tension in each of the three strains of rats tested with the Fa/fa group showing the greatest change and fastest rate of tension development. [Met] enkephalin, [Leu] enkephalin, DAMEA or DALEA (4 X 10(-6)M) infused concurrently with NA or isoprenaline (10(-6)M) evoked atrial tension changes within each group that were not different from those observed when NA or isoprenaline was administered alone. Carbachol (10(-9) and 10(-8)M) caused a dose-related decrease (10% and 30-40%, respectively, from pre-injection control values) in atrial tension in auricles excised from all three groups. Again, infusion of [Met] enkephalin, [Leu] enkephalin, DAMEA or DALEA (4 X 10(-6)M) together with carbachol (10(-8)M) did not affect atrial tension changes of auricles isolated from any group compared to when carbachol was given alone. The results indicate that the endogenous pentapeptides, [( Met] or [Leu] enkephalin), or derivatives (DAMEA and DALEA) do not affect atrial tension of electrically-stimulated auricles isolated from Sprague-Dawley, fa/fa or Fa/fa rats. In addition, these pentapeptides do not modify the positive inotropic actions of NA or isoprenaline or the negative inotropic effects of carbachol. It is suggested that in vivo, the enkephalins or enkephalin derivatives do not have a direct action on the heart to alter myocardial contractility.