enkephalin--leucine-2-alanine and Coronary-Disease

The aim of this study was to evaluate the effect of dalargin on the state of lipid peroxidation (LPO) and antioxidant system in patients with coronary heart disease (CHD) and on the background of metabolic syndrome (MS) in a group of 123 patients with stable coronary artery disease and MS (mean age 56.7 ± 5.1 years). For this purpose, the blood redox potential (EP), total antioxidant activity (TAA), level of oxidized low density lipoproteins (LDL), and activity of superoxide dismutase (SOD) were compared between the group receiving a standard medical therapy (ST) for coronary heart disease (group 1, n = 63) and that with supplementary dalargin administration (ST + D) in a dose of 1 mg intranasally twice a day for 10 days (group 2, n = 60), using the same dose for 10 days in the next two months (total 3 courses over 3 months). It was found that patients with CHD + MS upon 3-month ST showed no statistically significant changes in parameters characterizing the oxidative potential of blood (EP) and antioxidant protection of blood (oxidized LDL level, SOD activity). The inclusion of dalargin into therapy (ST + D) led to a significant decrease in the oxidative stress parameters (blood EP by 10.5%, oxidized LDL level by 14%, p < 0.001) and increase in the blood antioxidant properties (SOD activity by 36.1%, TAA by 25.3%, p < 0.001).

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Coronary Disease; Enkephalin, Leucine-2-Alanine; Female; Humans; Lipid Peroxidation; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged

The antiarrhythmic activities of 16-methylcyprenorphine (M8008), nor-binaltorphimine (NBT) and naltrexone, which are relatively specific opioid receptor antagonists for delta, kappa and mu receptors, respectively, were examined during the 30 min following coronary artery occlusion in anaesthetised rats. The haemodynamic and electrocardiographic effects of the opioid receptor agonists [D-Ala2,D-Leu5]enkephalin (DADLE) (relatively selective for delta receptors), ICI-204448 (kappa) and glyol (mu) were also investigated over the 30-90 min post ligation period. When administered intravenously 5 min before ligation, M8008 (0.5 mg kg-1 and 2.5 mg kg-1) reduced the number of ventricular ectopic beats but had no effect on the incidence or duration of ventricular fibrillation. NBT and naltrexone were not antiarrhythmic at a dose of 0.5 mg kg-1 but at 2.5 mg kg-1 (a concentration at which both drugs block kappa receptors) the number of ventricular ectopic beats, the incidence of ventricular fibrillation and mortality were all reduced. All of the opioid receptor agonists caused a transient decrease in heart rate and in arterial blood pressure but none exhibited an arrhythmogenic effect. These studies suggest that the delta and kappa opioid receptor antagonists used may be antiarrhythmic as a result of blockade of the action of endogenously released peptides acting on these receptors or that they have a non-specific 'direct' antiarrhythmic action.

Topics: Animals; Arrhythmias, Cardiac; Coronary Disease; Coronary Vessels; Electrophysiology; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine-2-Alanine; Enkephalins; Hemodynamics; Male; Morphinans; Naltrexone; Narcotic Antagonists; Pyrrolidines; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu

In cat experiments, the effects of dalargin were examined on blood pressure in the animals with its various baseline levels and on the development of ischemic arrhythmias. Dalargin was demonstrated to produce a modulating effect on blood pressure and to reduce the incidence of ventricular fibrillation in myocardial ischemia.

Topics: Animals; Blood Pressure; Cats; Coronary Disease; Coronary Vessels; Disease Models, Animal; Enkephalin, Leucine-2-Alanine; Female; Male; Vasodilator Agents

Cardiac opioid receptors have been shown to be involved in the genesis of arrhythmias during ischemia and reperfusion. The present study was aimed at elucidating the receptor subtype(s) involved in arrhythmogenesis. Two series of experiments were conducted. In the first, effects of prototype opioid agonists, namely, (D-Ala2, NMe4, Gly-ol)-Enkephalin (DAGO), U50,488H and (D-Pen2, Pen5)-Enkephalin (DPDPE) and (D-Ala2, D-Leu2)-Enkephalin (DADLE), representing mu-, kappa- and delta-agonists, respectively, in disturbing the normal cardiac rhythm in the isolated perfused rat heart were investigated. Both DAGO and U50,488H were arrhythmogenic, whereas the effects of the delta-agonists, DPDPE and DADLE at a same dose range (44-396 nmol/heart) as that of DAGO were almost negligible. U50,488H was by far the most potent as it induced ventricular arrhythmias including frequent PVC and VT even at a dose (44 nmol/heart) at which other agonists either produced no or negligible effect. In the second series of experiments, the antiarrhythmogenic effects of mu-antagonist (naloxone) and kappa-antagonist (MR 2266) against arrhythmias arising during ischemia and reperfusion were compared. The effects of MR 2266 were significantly greater than that of naloxone. Results of the present study suggest that the cardiac kappa-receptors are the most likely receptor-subtype involved in arrhythmogenesis during ischemia and reperfusion.

Topics: Animals; Arrhythmias, Cardiac; Benzomorphans; Coronary Disease; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Enkephalin, Leucine-2-Alanine; Enkephalins; Female; In Vitro Techniques; Myocardial Reperfusion Injury; Myocardium; Perfusion; Rats; Rats, Inbred Strains; Receptors, Opioid

Topics: Adult; Coronary Disease; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Extremities; Humans; Ischemia; Male; Microcirculation; Middle Aged; Sympatholytics

The work presents the data on the immunostimulating properties of neuropeptides. As revealed in this study, the leu-enkephalin level in blood sera (taken from 55 patients) inversely correlates with the intensity of the proliferative response of lymphocytes to phytohemagglutinin. In in vitro systems dalargin promotes the increase or decrease of the proliferative response of lymphocytes to phytohemagglutinin, depending on the proliferative activity of cells in response to this mitogen, and also leads to an increase in the number of rosette-forming cells. Leu-enkephalin in doses of 100, 10, 1, 0.1 micrograms/ml and dalargin in a dose of 0.1 microgram/ml inhibit the migration of leukocytes.

Topics: Adjuvants, Immunologic; Cell Migration Inhibition; Cells, Cultured; Coronary Disease; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Humans; Lymphocytes; Neuropeptides; Rosette Formation

It has been shown in experiments on albino rats that acute myocardial ischemia (AMI) produces a noticeable increase in excretion of adrenaline, noradrenaline, DOPA and dopamine with urine. Intraperitoneal injection of leu-enkephalin analogs (D-Ala2-Leu5-Arg6 and D-Ala2-D-Leu5-D-Arg6) to rats with AMI was accompanied by a noticeable prevention of activation of the sympathoadrenal system.

Topics: Adrenal Glands; Animals; Catecholamines; Coronary Disease; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalins; Male; Rats; Sympathetic Nervous System; Time Factors

It has been demonstrated in experiments on rats that acute myocardial ischemia gives rise to a decrease in diuresis, elevation of antidiuretic activity of blood plasma and the blood concentration of immunoreactive aldosterone. Intraperitoneal injection of a synthetic enkephalin analog D-ala2-leu5-arg6-enkephalin in a dose of 1.25 nmol/kg bw resulted in partial normalization of diuresis, reduction in antidiuretic activity of blood plasma and blood aldosterone level to the control values. Naloxone eliminated the effects described. It is concluded that enkephalins have an inhibitory action on aldosterone and vasopressin secretion, with this action being mediated via opiate receptors.

Topics: Aldosterone; Animals; Coronary Disease; Diuresis; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Male; Naloxone; Rats; Vasopressins

Topics: Adult; Aged; Blood Pressure; Coronary Disease; Dose-Response Relationship, Drug; Drug Evaluation; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Heart Rate; Hemodynamics; Humans; Middle Aged; Myocardial Contraction; Stroke Volume