Cardioprotective effects of stimulation of peripheral μ-opiate receptors and the role of opiatergic mechanisms in the pathogenesis of stress-induced heart damage

Immobilization induces stress damage to the heart. DAGO, an agonist of μ-opiate receptors potentiates, while an agonist of peripheral μ-opiate receptors prevents this damage. Naltrexone reduces, while methylnaltrexone, an inhibitor of peripheral μ-opiate receptors, potentiates the stress-induced damage to the heart. Other opiate ligands have no effect on heart damage. It is suggested that the stress-induced damage to the heart is promoted by activation of central μ-opiate receptors and prevented by stimulation of peripheral μ-opiate receptors. Translated fromByulleten'Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 3, pp. 276–278, March, 1997     

Activation of μ-opiate receptors as a factor of regulation of heart resistance to ischemia-reperfusion and oxidative stress

Intravenous injection of the selective μ-opiate receptor agonist DAMGO (0.1 mg/kg, 15 min before isolation of the heart) improved resistance of isolated perfused rat heart to ischemia (45 min) and reperfusion (60 min) damages.In vivo administration of DAMGO prevented reperfusion-induced damages to cardiomyocytes and decreased the content of conjugated dienes in the myocardium during ischemia-reperfusionin vitro. Furthermore, stimulation of μ-opiate receptors promoted recovery of myocardial contractility during reoxygenation, but had no effect on heart resistance to free radical-induced damages during perfusion of isolated heart with a solution containing Fe²⁺ and ascorbic acid.     

Effect of μ-opiate receptor agonist tetrapeptide A10 on DNA synthesis and protein content in the myocardium of albino rats

Effect of intraperitoneal injection of tetrapeptide A10 (H-Tyr-D-Orn-Phe-Gly-OH), selective μ-opiate receptor agonist, synthetic analog of dermorphine, in a dose of 100 μg/kg on DNA synthesis and protein content in the myocardium was studied in albino rats. Five injections of tetrapeptide on days 2–6 after birth caused no changes in DNA synthesis 17 days after the last injection,i. e. in 24-day rats. The number of nucleoli and their area increased. In adult males long-term (3-week) treatment with tetrapeptide A10 increased the number of nucleoli and the mean and integral optical density of isolated cardiomyocytes stained with amido black B, which probably attested to activation of protein synthesis in the myocardium. Simultaneously, the content of catecholamines in the heart increased. These data are comparable with delayed effects of κ-opiate receptor agonist dinorphine A_1–13 and indicate that morphogenetic properties of opioid peptides in rat myocardium are realized via the same routes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 12, pp. 693–695, December, 2000     

Role of vagus nerves in antiarrhythmic effect of DAGO in acute myocardial ischemia

Acute experiments on cats show that DAGO, a selective μ-opiate receptor agonist, elicits a pronounced antiarrhythmic effect in ischemia-induced arrhythmias. The protective effect of DAGO is observed only under conditions of intact parasympathetic innervation of the heart and apparently depends on then. vagus activity and stimulating effect of DAGO on acetylcholine release. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 10, pp. 377–379, October, 1997     

Prevention of experimental epinephrine-induced arrhythmias with agonists of δ1- and δ2-opiate receptors

Agonists of δ₁- and δ₂-opiate receptors prevent epinephrine-induced arrhythmias in rats after intracerebroventricular administration. The antagonist of δ-opiate receptors ICI 174,864 blocks antiarrhythmic effect of the selective agonist of δ-opiate receptors DTLET and exhibits no antiarrhythmic activity by itself. It is shown that antiarrhythmic effect of DTLET is associated with increased vagal tone. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 9, pp. 286–288, September, 1997     

Role of σ-opiate receptors in development of ischemic arrhythmias

In acute experiments on anesthetized cats, the selective σ-opiate receptor agonist DSLET has a pronounced antiarrhythmic effect on ischemic heart rhythm disturbances. This effect is probably related to inhibition of the sympathetic heart rhythm regulation, because the antifibrillation effect of DSLET is not mediated via the vagus nerves, but on the other hand DSLET considerably modulates cardiac adrenoreactivity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 2, pp. 164–167, February, 1999.     

Peripheral μ-Opiate receptors and modulation of myocardial tolerance to arrhythmogenic stimuli

The peripheral μ-opiate receptor agonists DALDA and PL017 are highly effective against arrhythmias induced by adrenaline, aconitine, or CaCl₂. The effect was abolished by the μ-opiate receptor antagonist CTAP. It is likely that Ca-channel block is involved in antiarrhythmic effect of DALDA. Translated fromByulleten' Eksperimental'noi Biologii 1 Meditsiny, Vol. 125, No. 6, pp. 650–653, June, 1998     

Opiatergic mechanisms of the cardiotropic effect of acute cooling

Changes in myocardial contractility after an acute cold exposure following intracerebroventricular administration of opiate receptor agonists were studied in rat hearts isolated after Langendorff. Cold exposures were carried out individually for each animal in chambers at −10°C for 4 h. Thirty min before being exposed to cold the animals were administered in a brain ventricle 10 μl of μ- or δ-opiate receptor agonists (DAGO or DADLE, respectively). Isolation and perfusion of the hearts were performed directly after the cold exposure was over. The mechanism of reduction of myocardial contractility and coronary flow induced by an acute cold exposure is believed to include stimulation of μ-opiate receptors as one of its main components, and the effect of intracerebral hypertension on hemodynamic parameters is partially mediated through activation of δ-opiate receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 582–584, December, 1994 Presented by R. S. Karpov, Member of the Russian Academy of Medical Sciences     

The contribution of dopamine autoreceptors to the reactivating effect of opioid antagonists

The dopamine-opioid interaction is analyzed in amnesia and forgetfulness with the use of passive avoidance conditioning in experiments on mice. Naloxone or ICI174.864 administration restored the conditioned response in both learning situations against the background of saline. Pretreatment with (+)3PPP eliminated the reactivating effects of μ- and δ-opiate receptor blockade in the case of amnesia. The activation of dopamine autoreceptors in forgetfulness disrupted the memory restoration induced by ICI174.864, but not that by naloxone. The findings attest that reactivation of an amnestied memory trace by opioid receptor blockade depends on dopaminergic system functioning, whereas in the case of forgetfulness dopamine-opioid interactions are probably determined by the functional heterogeneity of the μ- and δ-opiate receptors and diminished contribution of the dopamine system to the process. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, No. 2, pp. 120–124, February, 1995 Presented by V. A. Trufakin, Member of the Russian Academy of Medical Sciences     

Contribution of μ- and δ-opiate receptors into vagotropic effect of met-enkephalin

In anesthetized cats met-enkephalin affects the initial cardiac rhythm and synchronizing component of vagal chronotropic control via excitation of δ-opiate receptors and modulates tonic inhibitory vagal control via activation of both δ- and μ-opiate receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 11, pp. 502–505, November, 1998     

Central κ1 receptors and mechanisms of arrhythmogenesisreceptors and mechanisms of arrhythmogenesis

Agonists of κ₁-opiate receptors injected in brain ventricle potentiate arrhythmogenic effect of adrenaline. Antagonist of κ₁-opiate receptors norbinaltorphimine or ganglioblocker hexamethonium completely abolish proarrythmic effects of κ₁-agonists. Norbinaltorphimine possesses intrinsic antiarrhythmic activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 6, pp. 656–658, June, 1997     

Participation of opioid and serotoninergic brain receptors in amphetamine-induced stereotypy and hyperthermy

The inbred rat strains WAG and Fischer-344 were found to differ in the duration of amphetamine-induced stereotypy and the degree of hyperthermy elicited by this drug, the stereotypy lasting longer in WAG rats and the hyperthermy being more pronounced in Fischer—344 rats. A comparison of interstrain differences in the amphetamine effects, in receptor binding, and in the pharmacological activity of receptor agonists suggests that the μ-opiate system of the brain may be involved in the manifestation of amphetamine-induced stereotypy, while its serotoninergic system may mediate the elevation of body temperature caused by this drug. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 9, 242–243, September, 1995 Presented by V. N. Yarygin, Member of the Russian Academy of Medical Sciences     

Antiarrhythmic effects of μ-opiate receptor agonists in rats with epinephrine-induced arrhythmias: Role of the vegetative nervous system

The μ-opiate receptor agonists DAGO and DALDA preinjected intravenously in a dose of 0.1 mg/kg prevented the occurrence of arrhythmias in rats injected with epinephrine. Their antiarrhythmic activity was not modified by atropine or hexamethonium. It is concluded that the vegetative nervous system plays no substantial role in mediating the antiarrhythmic effects of DAGO and DALDA, and that these effects are most likely associated with stimulation of cardiac opiate receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 25–27, July, 1996     

Central κ1-opiate receptors and mechanisms of arrhythmias-opiate receptors and mechanisms of arrhythmias

Intracerebroventricular infusion of κ₁-opiate receptor agonists potentiated cardiac arrhythmias elicited by epinephrine. This effect was completely reversed by the κ₁-receptor antagonist norbintaltorphymine and the ganglioblocker hexamethonium. Norbintaltorphymine also exhibited an antiarrhythmic activity. It is suggested that endogenous ligands of κ₁-receptors play an important role in the regulation of arrhythmias. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 1, pp. 57–59, January, 1999.     

Opiatergic mechanisms of cardioprotective and antiarrhythmic effects of adaptation

Adaptation to hypoxia and short-term immobilization stress, as well as preconditioning with Rhodiolae rosea extract produces pronounced antiarrhythmic and cardioprotective effects in the model of adrenergic damage to the heart. Preliminary blockade of opioid receptor significantly decreases the protective effect of adaptation. Using selective opiate receptor antagonists (naltrindole, ICI 174,864, and norbinaltorphimine) we show that the antiarrhythmic effect of adaptation is mediated predominantly via activation ofk-receptors, and to a lesser extent μ-and σ-receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 2, pp. 167–170, February, 1999     

The effect of μ-and σ-opiate receptor agonists on cell division of corneal and tongue epithelium in albino rats

The effect of μ- and σ-opiate receptor agonists at 10 μg/kg on the processes of cell division in corneal and tongue epithelium of albino rats is studied using the method of autoradiography with³H-thymidine. The ligand of the μ-receptors causes the inhibition of DNA synthesis in corneal epithelium 4, 12, and 24 h later and lowers the mitotic index after 4 and 24 h. In contrast, in the tongue epithelium stimulation of the proliferative processes occurs. Ligand of the σ-receptors stimulates DNA synthesis in corneal epithelium after 12 and 24 h and cell division after 12 h. In the tongue epithelium DNA synthesis is activated after 4, 12, and 24 h and cell division after 12 h. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 5, pp. 533–535, May, 1994 Presented by Yu. A. Romanov, Member of the Russian Academy of Medical Sciences     

Modulating effect of μ-opiate receptor ligands on adrenergic stage in pathogenesis of stress-induced damage to the heart

The agonists of μ-opiate receptors, DAGO and DALDA, prevent stress-induced enhancement of^99mTc-pyrophosphate accumulation in the myocardium, which attests to cardioprotective activity of these opioids. This phenomenon is presumably related to modulating effect of these agents on the adrenergic stage in pathogenesis of stress-induced damage to the heart. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 11, pp. 510–512, November, 1998     

On the involvement of endogenous μ- and δ-opiate receptor agonists in the antiarrhythmic effect of adaptation

Rats adapted to stress showed a decreased severity and incidence of cardiac arrhythmias induced by epinephrine, and these effects of adaptation were abolished by naloxone. It is suggested that stress adaptation mitigates arrhythmia by activating the endogenous opioid system and stimulating the μ-opiate receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 1, pp. 24–25, January, 1996 Presented by R. S. Karpov, Member of the Russian Academy of Medical Sciences     

Anxiolytic effect of dalargin on rat behavior in Vogel's conflict test and in elevated plus-maze

The anxiolytic effects of the δ-opioid receptor agonist dalargin revealed in two behavioral tests in outbred albino rats were blocked by naloxone. The effect of dalargin depended on the initial locomotor activity and was observed after central and peripheral administration of the drug. The μ-opioid receptor agonist DAGO produced no behavioral effects. It is suggested that the development of behavioral manifestations of anxiety and phobia is related to more than one opioid-dependent mechanism, which can explain the peculiarities of the anxiolytic effect of dalargin. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 2. pp. 211–214, February 1999     

Do endogenous ligands of peripheral μ- and δ-opiate receptors mediate antiarrhythmic and cardioprotective effects ofRhodiola rosea?

Oral administration ofRhodiola rosea extract to rats (3.5 ml/kg, 8 days) prevents reperfusion arrhythmias and elicits a protective effect in experiments on isolated heart. Experiments with naloxone and ICI 174,864 suggest that the antiarrhythmic effect ofR. rosea extract is mediated through activation of μ-opiate receptors in the myocardium. The cardioprotective effect of this extract is not associated with opiate receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 8, pp. 151–153, August, 1997