[Vascular effects of ginseng compounds].

In the review it has been systematized data on the vascular effects of ginsenosides in vivo. It has been shown that ginsenosides increase a tolerance of isolated arteries to oxidative stress, hypoxia-reoxigenation, homocysteine and other pathogenic factors. It has been performed an analysis published works on the effects of triterpene saponines on the NO synthesis in the isolated endothelial cells, a proliferation of these cells, an apoptosis of endotheliocytes, a secretion of vascular endothelial growth factor by endothelial cells. It was exhibited data on the potency of ginsenosides to inhibit a proliferation of vascular smooth muscle cells. It has been discussed a molecular mechanisms of triterpene saponines action, their interaction with steroid hormone receptors, proteinkinases, NO-synthase, guanilyl cyclase, K(Ca)-channels, Ca(2+)-channels.

[Cardioprotective, inotropic, and anti-arrhythmia properties of a complex adaptogen "Tonizid"].

We have studied the new complex plant adaptogen preparation tonizid containing dry extracts of Aralia mandshurica, Panax ginseng, Rhodiola rosea, and Eleutherococcus senticosus. The course administration (5 days) of tonizid led to a decrease in the ratio of necrotic zone size/risk area during a 45-min local ischemia and a 2-hr reperfusion in artificially ventilated chloralose anaesthetized rats. This compound decreased the necrotic zone but did not change the size of the risk area. Tonizid also prevented an appearance of ventricular fibrillation during a 45-min coronary artery occlusion, but did not affect the incidence of ventricular arrhythmias during a brief ischemia and reperfusion. In a separate series of experiments, tonizid was administered during 5 days to rats with postinfarction cardiac sclerosis, which was formed 45 days after coronary artery occlusion. In this case, tonizid dose-dependently elevated the ventricular fibrillation threshold. The experiments in vitro were performed on a model of 35-min total ischemia and 30-min reperfusion of isolated rat heart using the Langendorff technique. The course administration of tonizid attenuated the reperfusion-induced decrease in the left ventricular pressure and the rate of contraction. However, tonizid did not prevent a reperfusion-induced reduction in the heart rate, a decrease in the rate of relaxation, and an increase in the final diastolic pressure. Tonizid decreased the creatine kinase levels in the venous effluent from isolated rat heart during reperfusion. At the same time, the plant adaptogen did not affect the incidence of ventricular arrhythmias and coronary flow. It is suggested that tonizid can be used as an adaptogen drug attenuating the contractility dysfunction and preventing an appearance of irreversible cardiomyocyte damage during ischemia and reperfusion. Tonizid exhibits cardioprotective and antifibrillatory properties during acute cardiac ischemia/reperfusion and postinfarction cardiac fibrosis.

[Cardioprotective and antiarrhythmic properties of Rhodiolae roseae preparations].

It is established that the chronic administration of Rhodiola rosea extract (RRE) in a single daily dose of 1 ml/kg (p.o.) during 8 days increased the resistance of myocardium with respect to the cardiotoxic action of isoproterenol and the arrhythmogenic action of epinephrine in rats. Pretreatment with RRE prevented the stressor cardiac damages, as measured by 99mTc-pyrophosphate accumulation in the heart. The cardioprotective action of RRE was maximum after 5-day administration. The antiarrhythmic effect of the adaptogen was maximum after 8-day administration. It was found that p-tyrosol also exhibited antiarrhythmic and cardioprotective properties. Pretreatment with RRE decreased the infarction size/risk area ratio during the coronary artery occlusion and reperfusion in vivo. The chronic administration of RRE increased th e tolerance of the isolated perfused rat heart to the pathogenic action of global ischemia and reperfusion. Pretreatment with RRE not only prevented the occurrence of arrhythmias, but also abolished cardiac electrical instability in rats with postinfarction cardiac sclerosis. It has been found that the chronic administration of RRE (1 ml/kg, p.o., over 8 days) increased the level beta-endorphin in rat blood plasma and the content of leu-enkephalin in myocardial tissue. Naloxone (2 mg/kg) abolished cardioprotective and antiarrhythmic effect of the adaptogen. It was suggested that both RRE effects depend on the occupancy of opioid receptors by endogenous opioid peptides. It has been found that the sympathetic nervous system is involved in the development of antiarrhythmic effect of RRE, while HSP-70 is not involved in the cardioprotective and antiarrhythmic effect of adaptogen. It is concluded that the mechanism of cardioprotective and antiarrhythmic action of RRE needs further investigation.

[The anti-arrhythmia and pro-arrhythmia properties of sigma-receptor ligands]. / Antiaritmicheskie i proaritmicheskie svoistva ligandov sigma-retseptorov.

It has been found that the sigma 1- and sigma 3-receptor antagonists, DuP 734 intraperitoneally and XJ 448 intravenously, had antiarrhythmic effects against epinephrine-induced arrhythmias in rats. The ED50 for antiarrhythmic effect of DuP 734 was 0.157 mg/kg after intraperitoneal administration. Other sigma-receptor antagonists (rimcazole, BMY 14802, haloperidol) did not affect the incidence of epinephrine-induced arrhythmias. sigma 1-Receptor agonists (DTG, N-allyl-normetazocine, (+)-3-PPP, (-)-3-PPP) had proarrhythmic effect after systemic administration. The sigma-agonist N-allyl-normetazocine and sigma-antagonist XJ 488 had no effect on the incidence of epinephrine-induced arrhythmias after intracerebroventricular administration. Therefore, it appears that the central nervous system does not play a significant role in the antiarrhythmic or proarrhythmic effects of sigma ligands. We hypothesize that these effects of sigma ligands might be dependent on their action on cardiac sigma receptors.

The anti-arrhythmia properties of the functional opioid agonist orphanin FQ (nociceptin). / Antiaritmicheskie svoistva funktsional'nogo agonista opioidov orfanina FQ (notsitseptina).

It was shown that the agonist of peripheral ORL1 receptors nociceptine raises heart resistance to the antiarrhythmic effect of aconitine. The antiarrhythmic effect of nociceptine is not connected with a change in the tonus of the autonomous nervous system or with an effect on opiate receptors. It is assumed that the antiarrhythmic properties of nociceptine are realized through inhibition of Na+/Ca2+ metabolism or blockade of rapid Na(+) channels of the cardiomyocytes.

[The anti-arrhythmic activity of agonists of the peripheral mu-opiate receptors]. / Antiaritmicheskaia aktivnost' agonistov perifericheskikh mu-opiatnykh retseptorov.

It was shown that the agonists of peripheral mu-receptors DALBA and PLO17 increase the resistance of the heart to adrenaline, aconitine, ischemic, reperfusion, and CaCl2-induced arrhythmias and also raise the threshold of ventricular fibrillation in postinfarction cardiosclerosis. The antagonists of mu-receptors naloxon and STAR removed these effects. The ganglion-blocking agent hexamethonium had no influence on the antiarrhythmic effect of DALBA. It is supposed that the autonomic nervous system does not play any essential role in the mechanism of the antiarrhythmic effect of agonists of peripheral mu-receptors.

[Modulation of the antiarrhythmic effect by endogenous opioids during adaptation to hypoxia in rats]. / O moduliruiushchem vliianii éndogennykh opioidov na antiaritmicheskii éffect pri adaptatsii krys k gipoksii.

Adaptation of rats to hypoxia increased the heart resistance against arrhythmogenic effects. The Met-enkephaline-Arg6-Phe7 contant increased in the hypothalamus of the adapted animals. The blockers of mu- and delta-opioid receptors reduced the antiarrhythmic effect of the adaptation, whereas chi-receptor inhibitor, nor-binaltorphimine, completely abolished it. The findings suggest the antiarrhythmic effect depends on an increase of the endogenous opioids level and modulated effect of these peptides upon autonomous nervous system.

[Contribution of the opioid system to realization of inotropic effects of Rhodiola rosea extracts in ischemic and reperfusion heart damage in vitro]. / Uchastie opioidnoi sistemy v realizatsii inotropnykh effektov ekstrakta rodioly rozovoi pri ishemicheskikh i reperfuzionnykh povrezhdeniiakh serdtsa in vitro.

It has been established that a course of oral administration of Rhodiola rosea extract in a dose of 3.5 mg/kg prevents reperfusion decrease in contraction amplitude of the isolated perfused rat heart. It also prevents reduction of coronary flow and development of contracture in the postischemic period. Intravenous infusion of naloxone (0.5 mg/kg) completely abolishes the favorable effect of Rhodiola in relation to the heart contractility and coronary flow parameters. The protective effect of Rhodiola may probably be connected with increase in the level of endogenous opioid peptides.

[The anti-arrhythmic effect of the selective sigma-receptor antagonist DuP 734 [1-(cyclopropylmethyl)-4-(2'-(4''-fluorophenyl)-2'-oxoethyl)piper idine HBr]]. / Antiaritmicheskii éffekt selektivnogo antagonista sigma-retseptorov DuP734 [1-(tsiklopropilmetil)-4-(2'-(4''-fluorofenil)-2'-oksoétil)piperidin HBr].

It was demonstrated on models of epinephrine-, CaCl2-, and aconitine-induced arrhythmias that the sigma-receptor antagonist DuP734 possesses high antiarrhythmic activity in a dose of 1 mg/kg. The sigma-receptor agonist-(+)SKF10,047 promoted the development of ventricular fibrillation. Atropine had no effect on the antiarrhythmic properties of DuP734. "Chemical sympathectomy" of the myocardium with the ganglion-blocking agent hexamethonium also did not affect the proarrhythmic properties of (+)SKF10,047. It is supposed that selective sigma-receptor blocking agents may be highly effective antiarrhythmic drugs.

[The participation of the mu-, delta- and kappa-opioid receptors in the realization of the anti-arrhythmia effect of Rhodiola rosea]. / Ob uchastii mu-, del'ta- i kappa-opioidnykh retseptorov v realizatsii antiaritmicheskogo éffekta rodioly rozovoi.

A course of the adaptogen extractum Rhodiola rosea (3.5 ml/kg given per os daily for 8 days). produces am antiarrhythmic effect on models of epinephrine-induced arrhythmia. Blockade of mu-opiate receptors (OR) by naloxone (0.2 mg/kg) and delta-OR by ICI 174.864 (2.5 mg/kg) had no effect on the resistance of the heart of rats adapted to epinephrine. Higher doses of naloxone reduced significantly the antiarrhythmic effect of extr. Rhodiola. The antiarrhythmic effect of the extract is assumed to be related to activation of the opioid system and stimulation of kappa-OR.

[The mechanism of the anti-arrhythmia action of mu-opioid-receptor agonists in a model of CaCl2-induced arrhythmias: the role of the autonomic nervous system]. / Mekhanizm antiaritmicheskogo deistviia agonistov mu-opiatnykh retseptorov na modeli CaCl2-indutsirovannykh aritmii: rol' vegetativnoi nervnoi sistemy.

It was established that selective ligands of the mu-opioid receptors DAGO and DALDA exhibit antiarrhythmic activity on a model of CACl2-induced arrhythmias when infused intravenously in a dose of 0.2 mg/kg. The autonomic nervous system does not take part in realization of the antiarrhythmic effect of DAGO and DALDA. It is supposed that this effect of DAGO and DALDA is associated with activation of cardiac mu-opioid receptors.

[The participation of the central and peripheral kappa-opiate receptors in the mechanism of the anti-arrhythmia action of benzeneacetamide derivatives]. / Ob uchastii tsentral'nykh i perifericheskikh kappa-opiatnykh retseptorov v mekhanizme antiaritmicheskogo deistviia proizvodnykh benzeneatsetamida.

When injected intraperitoneally in a dose of 8 mg/kg, U-62066, the selective agonist of kappa-opioid receptors, exhibits antiarrhythmic properties in epinephrine-induced arrhythmias in rats. In cerebroventricular injection, the kappa-agonists U-50,488 and [D-ala2]-dynorphin A(1-13) manifest proarrhythmic properties. Preliminary administration of the kappa-antagonist nor-binaltorphimine completely removes the proarrhythmic and antiarrhythmic effect of kappa-agonists. The antiarrhythmic effect of U-62006 is believed to be associated with activation of peripheral kappa-receptors.

[An experimental study of the pharmacological activity of opiate receptor ligands on models of adrenaline-induced arrhythmias]. / Eksperimental'noe izuchenie farmakologicheskoi aktivnosti ligandov opiatnykh retseptorov na modeli adrenalinovykh aritmii.

The influence of intracerebroventricular injection of opioid peptides on the incidence and severity of ventricular arrhythmia induced by intravenous administration of epinephrine was studied. It was found that DAGO, a selective mu-agonist, and DADLE, a nonselective delta-agonist, reduce the incidence and severity of cardiac arrhythmia in rats. On the contrary, DSLET, a selective delta-agonist, and Dynorphin A 1-13 (kappa-agonist), potentiates epinephrine-induced arrhythmias. beta-Endorphin do not affect the arrhythmia. The activation of cerebral mu-opioid receptors is shown to prevent the appearance of arrhythmia. On the contrary, the activation of delta- and kappa-receptors induces the appearance of arrhythmia.

[The cardioprotective and antiadrenergic activity of an extract of Rhodiola rosea in stress]. / O kardioprotektornoi i antiadrenergicheskoi aktivnosti ékstrakta rodioly rozovoi pri stresse.

The course of administration of Rhodiola rosea extract was studied for effects on the pattern of stress-induced cardiac damage which was assessed by 99mTc-pyrophosphate accumulation in the heart. Rhodiola rosea was found to prevent stress-induced cardiac damage. Simultaneously, myocardial catecholamines and cAMP levels were measured. Rhodiola rosea was ascertained to prevent both stress-induced catecholamine release and higher cAMP levels in the myocardium. Moreover, the adaptogen prevented lower adrenal catecholamines during stress. The findings suggest that the antistressor and cardioprotective effects of Rhodiola rosea are associated with limited adrenergic effect on the heart.

[Cardiac contractile function following acute cooling of the body and the adaptogenic correction of its disorders]. / Sokratitel'naia funktsiia serdtsa posle ostrogo okhlazheniia organizma i adaptogennaia korrektsiia ee narushenii.

In experiments on white Wistar rats the effect of acute 4-hour freezing at -10 degrees C on contractile function of the hearts isolated by the Langendorff technique, and the protective efficacy of Rhodiola rosea extract were investigated. The obtained results testify to the fact that acute cooling leads to a decrease in myocardial contractile activity that recovers during 18 hours. But this recovery cannot be complete as it does not result in stable contractility of isolated heart in perfusion. Preliminary adaptation of animals during treatment with Rhodiola rosea extract prevents the decrease in contractility force immediately after acute cooling and contributes to the stable contractility during 60 minutes of perfusion. Moreover, Rhodiola rosea extract does not remove the disturbance in diastolic function and in all cases leads to a decrease in coronary blood flow. The effect of Rhodiola rosea extract on the myocardium is likely to be similar to that of myocardial recovery after acute cooling.