enkephalin--ala(2)-mephe(4)-gly(5)- and Myocardial-Ischemia

The therapeutic potential of cardiac μ-opioid receptors in ischaemia-reperfusion (I/R) injury during opioid-modulating diseases, such as heart failure, is unknown. We aimed to explore the changes of cardiac μ-opioid receptor expression during heart failure, and its role in opioid-induced cardioprotection.. Cardiac μ-opioid receptor mRNA concentrations were 3.2 times elevated in DOX-treated rats compared with NS rats, while cardiac μ-opioid receptor protein concentrations showed 6.1- and 3.5-fold increases in DOX-treated and post-infarcted rats, respectively. DAMGO reduced I/R-caused infarct size, expressed as the ratio of area at risk, from 0.50 (0.04) to 0.25 (0.03) in failing rat hearts, but had no effect on infarct size in control hearts. DAMGO promoted phosphorylation of ERK and glycogen synthase kinase (GSK)-3β only in failing hearts. DAMGO-mediated cardioprotection was blocked by an ERK inhibitor. The μ-opioid receptor antagonist D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) prevented morphine- and remifentanil-induced cardioprotection and phosphorylation of ERK and GSK-3β in failing hearts. In contrast, δ- and κ-opioid receptor selective antagonists were less potent than CTOP in the failing hearts.. Cardiac μ-opioid receptors were substantially up-regulated during heart failure, which increased DAMGO-induced cardioprotection against I/R injury.

Topics: Analgesics, Opioid; Animals; Antibiotics, Antineoplastic; Cardiotonic Agents; Chronic Disease; Coronary Vessels; Doxorubicin; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Glycogen Synthase Kinase 3; Heart; Heart Failure; Ligation; Male; MAP Kinase Signaling System; Morphine; Myocardial Infarction; Myocardial Ischemia; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Remifentanil

We studied the effects of μ-opioid receptor activation in vivo and in vitro on the tolerance of isolated perfused rat heart to global ischemia (45 min) and reperfusion (30 min). Stimulation of μ-receptors in vivo by intraperitoneal administration of μ-opioid receptor agonist DAMGO (0.1 mg/kg) reduced reperfusion release of creatinine phosphokinase and promoted aggravation of postischemic systolic and diastolic dysfunction of the isolated heart. Activation of μ-opioid receptors in vitro by addition of selective agonist DAMGO in a concentration of 170 nM to perfusion solution had no effect on necrotic death of cardiomyocytes and aggravated reperfusion stunning of the heart.

Topics: Animals; Cell Death; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Heart; Male; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; Necrosis; Organ Culture Techniques; Rats; Rats, Wistar; Receptors, Opioid, mu; Reperfusion

In acute experiments on Nembutal-anesthetized cats, the effect of opiate receptor agonists DAGO, DSLET, and dinorphin A(1-13) on the incidence of idioventricular rhythm disturbances, including ventricular tachycardia and fibrillation, was studied under conditions of occlusion of circumflex branch of the left coronary artery and stimulation of the sensorimotor cortex. The most pronounced effects were observed with DSLET and dinorphin A(1-13). These preparations completely prevented ventricular fibrillation. DAGO produced a less pronounced protective effect probably because of parallel increase in plasma catecholamine concentration.

Topics: Analgesics, Opioid; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cats; Dynorphins; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine; Motor Cortex; Myocardial Ischemia; Peptide Fragments; Receptors, Opioid

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cats; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalins; Female; Heart; Lasers; Male; Myocardial Ischemia; Myocardium; Opioid Peptides; Receptors, Opioid; Sympathectomy

Stimulation of mu-opioid receptors was found to contribute to prevention of myocardial contractile dysfunction and ventricular arrhythmias in ischemia and reperfusion of the rat isolated heart. Endogenous agonists of the mu-opioid receptors were not involved in tonic regulation of the heart resistance against reperfusion disturbances of the rhythm and contractility. On the other hand, mu-opioid receptors are important for development of postischemic contracture.

Topics: Animals; Blood Pressure; Electrocardiography; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; In Vitro Techniques; Ligands; Myocardial Ischemia; Myocardial Reperfusion Injury; Narcotic Antagonists; Oligopeptides; Peptides; Rats; Rats, Wistar; Receptors, Opioid, mu

Topics: Acute Disease; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cats; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Female; Male; Myocardial Ischemia; Nerve Fibers, Myelinated; Receptors, Opioid, mu; Vagotomy; Vagus Nerve