enkephalin--leucine-2-alanine and Ventricular-Fibrillation

The effects of the extremely selective mu-opioid receptor agonist, [D-Arg2,Lys4]-dermorphin-(1-4)-amide (DALDA), the mu-opioid receptor agonist morphine, the mu/delta agonist D-Ala2, Leu5, Arg6-enkephalin (dalargin), the kappa-opioid receptor agonist spiradoline, and the sigma1-receptor antagonist DuP 734 on ventricular fibrillation threshold (VFT) was investigated in an experimental post-infarction cardiosclerosis model and an immobilization stress-induced model in rats. Both models produced a significant decrease in VFT. The postinfarction cardiosclerosis-induced decrease in VFT was significantly reversed by intravenous administration of dalargin (0.1 mg/kg), DALDA (0.1 mg/kg), or morphine HCl (1.5 mg/kg). Pretreatment with naloxone (0.2 mg/kg) completely eliminated the increase in cardiac electrical stability produced by DALDA. Both spiradoline (8 mg/kg, i.p.) and DuP 734 (1 mg/kg, i.p.) produced a significant increase in VFT in rats with post-infarction cardiosclerosis. This effect of spiradoline was blocked by nor-binaltorphimine. The immobilization stress-induced decrease in VFT was significantly reversed by administration of either DALDA, spiradoline or DuP 734. In conclusion, activation of either mu- or kappa1-opioid receptors or blockade of sigma1-receptors reversed the decrease in VFT in both cardiac compromised models. Since DALDA and dalargin essentially do not cross blood brain barriers, their effects on VFT may be mediated through peripheral mu-opioid receptors.

Topics: Animals; Anti-Arrhythmia Agents; beta-Endorphin; Disease Models, Animal; Dynorphins; Enkephalin, Leucine-2-Alanine; Heart; Immobilization; Ligands; Morphine; Myocardial Infarction; Myocardium; Naloxone; Naltrexone; Narcotic Antagonists; Oligopeptides; Piperidines; Pyrrolidines; Rats; Receptors, Opioid; Receptors, Opioid, delta; Stress, Physiological; Ventricular Fibrillation

Topics: Adrenal Glands; Animals; Cold Temperature; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine-2-Alanine; Enkephalins; Heart; Histocytochemistry; Ligands; Myocardium; Rats; Rats, Wistar; Receptors, Opioid, delta; Receptors, Opioid, mu; Sympathetic Nervous System; Ventricular Fibrillation

Topics: Animals; Anti-Arrhythmia Agents; beta-Endorphin; Cats; Enkephalin, Leucine-2-Alanine; Female; Male; Motor Cortex; Myocardial Ischemia; Somatosensory Cortex; Tachycardia, Ventricular; Ventricular Fibrillation

Topics: Animals; Anti-Arrhythmia Agents; Blood Pressure; Cats; Enkephalin, Leucine-2-Alanine; Female; Heart Rate; Male; Myocardial Ischemia; Sympathectomy; Sympatholytics; Ventricular Fibrillation

It has been established that preliminary administration of D-Ala2-Leu5-Arg6-enkephalin, D-Met2-Pro5-enkephalinamide, and D-phenylalanine to experimental animals prevents a stress-induced increase of the content of thromboxane in the blood plasma and myocardium and induces a rise of the level of prostacyclin, PGF2 and PGE in the heart and blood plasma. The authors hold that the changes in the level of prostanoids may mediate cardioprotective and anti-stressor rather than antiarrhythmic effects of enkephalins.

Topics: Animals; Anti-Arrhythmia Agents; Disease Models, Animal; Drug Evaluation, Preclinical; Enkephalin, Leucine-2-Alanine; Enkephalin, Methionine; Heart; Myocardial Ischemia; Myocardium; Prostaglandins; Stress, Physiological; Ventricular Fibrillation

In acute experiments on cats it has been shown that dalargin possess antiarrhythmic affect in myocardial ischemia. Antiarrythmic effect of dalagrig may be connected both with reflex and with direct action of dalargin on neurons structure, which

Topics: Animals; Anti-Arrhythmia Agents; Cats; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Enkephalin, Leucine-2-Alanine; Female; Heart; Heart Rate; Male; Myocardial Ischemia; Vagotomy; Ventricular Fibrillation

Adaptation of rats to cold and physical exercise prevented ventricular fibrillation (VF) caused by the occlusion of the left anterior coronary artery. In the heart of adapted rats with acute myocardial ischemia, myocardial enkephalins increased whereas the level of cAMP declined as compared to nonadapted animals. Injection of dalargin before the occlusion of the coronary artery in rats prevented both VF and a decrease of VF threshold. The peptide averted the rise of cAMP content in the heart during acute myocardial ischemia. The data obtained suggest that the rise of endogenous myocardial enkephalins may have an important role in antiarrhythmic action of adaptation. It is assumed that antiarrhythmic effect of enkephalins may be related to the restriction of sympathetic influence on the heart.

Topics: Acute Disease; Adaptation, Physiological; Animals; Cold Temperature; Enkephalin, Leucine-2-Alanine; Enkephalins; Exercise; Heart; Male; Myocardial Ischemia; Myocardium; Nucleotides, Cyclic; Rats; Rats, Wistar; Sympatholytics; Ventricular Fibrillation

It was found, that injection of delta-receptors agonist dalargin before the occlusion of left anterior coronary artery in rats prevented the decrease of ventricular fibrillation threshold (VFT). An injection of naloxone in dose 0.5 mg/kg (for the blockade of mu-receptors only) had no influence on the VFT. Naloxone in dose 1 mg/kg (for the blockade peripheric mu- and delta-receptors) decreased VFT. An intraventricular infusion of dalargin (10 mkg) induced bradycardia and an increase of VFT. It was assumed that anti-arrhythmic effects of enkephalins in acute myocardial ischemia could be realized by an activation of peripheric delta-receptors and central mu-receptors.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Enkephalin, Leucine-2-Alanine; Enkephalins; Male; Myocardial Infarction; Naloxone; Rats; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, mu; Ventricular Fibrillation