RESUMEN
Coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats in vivo, as well as total ischemia (45 min) of an isolated rat heart followed by reperfusion (30 min) were reproduced. The selective δ2-opioid receptor agonist deltorphin II (0.12 mg/kg and 152 nmol/liter) was administered intravenously 5 min before reperfusion in vivo or added to the perfusion solution at the beginning of reperfusion of the isolated heart. The peripheral opioid receptor antagonist naloxone methiodide and δ2-opioid receptor antagonist naltriben were used in doses of 5 and 0.3 mg/kg, respectively. It was found that the infarct-limiting effect of deltorphin II is associated with the activation of δ2-opioid receptors. We have demonstrated that deltorphin II can improve the recovery of the contractility of the isolated heart after total ischemia.
Asunto(s)
Daño por Reperfusión Miocárdica , Receptores Opioides delta , Animales , Masculino , Ratas , Corazón/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Infarto del Miocardio/metabolismo , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/fisiopatología , Miocardio/metabolismo , Antagonistas de Narcóticos/farmacología , Oligopéptidos/farmacología , Ratas Wistar , Receptores Opioides delta/agonistas , Receptores Opioides delta/metabolismoRESUMEN
Hypoxia (20 min) and reoxygenation (30 min) were simulated on isolated rat cardiomyocytes to evaluate the cytoprotective effect of selective δ2-opioid receptor agonist deltorphin II, opioid receptor antagonist naloxone methiodide, µ-opioid receptor antagonist CTAP, κ-opioid receptor antagonist nor-binaltorphimine, ε1-opioid receptor antagonist BNTX, and δ2-opioid receptors naltriben. Deltorphin II was administered 5 min before reoxygenation, antagonists were administered 10 min before reoxygenation. The cytoprotective effect of deltorphin II was assessed by the number of cardiomyocytes survived after hypoxia/reoxygenation, as well as by the lactate dehydrogenase content in the incubation medium. It has been established that the cytoprotective effect of deltorphin II occurs at a concentration of 64 nmol/liter and is associated with activation of δ2-opioid receptors.
Asunto(s)
Antagonistas de Narcóticos , Receptores Opioides , Ratas , Animales , Antagonistas de Narcóticos/farmacología , Receptores Opioides delta/genética , Miocitos Cardíacos , Receptores Opioides mu , HipoxiaRESUMEN
A comparative analysis of the infarct-limiting activity of δ- and κ-opioid receptors (OR) agonists was carried out on a model of coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats. We used selective δ2-OR agonist deltorphin II (0.12 mg/kg), δ-OR agonists BW373U86 and p-Cl-Phe DPDPE (0.1 and 1 mg/kg), selective agonists of δ1-OR DPDPE (0.1 and 0.969 mg/kg), κ1-OR U-50,488 (0.1 and 1 mg/kg), κ2-OR GR-89696 (0.1 mg/kg), and κ-OR ICI-199,441 (0.1 mg/kg). All drugs were administered intravenously 5 min before reperfusion. Deltorphin II, BW373U86 (1 mg/kg), p-Cl-Phe DPDPE (1 mg/kg), U-50,488 (1 mg/kg), and ICI-199,441 had a cardioprotective effect. The most promising compounds for drug development are ICI-199,441 and deltorphin II.
Asunto(s)
Benzamidas , Reperfusión Miocárdica , Piperazinas , Receptores Opioides delta , Ratas , Animales , Masculino , Ratas Wistar , Encefalina D-Penicilamina (2,5) , InfartoRESUMEN
The signaling mechanism of the cardioprotective effect of deltorphin II was studied in models of coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats. We used the selective δ2-opioid receptor agonist deltorphin II (0.12 mg/kg), which was administered intravenously 5 min before reperfusion, the PI3K inhibitor wortmannin (0.025 mg/kg), the ERK1/2 blocker PD-098059 (0.5 mg/kg), the inhibitor JAK2 AG490 (3 mg/kg). All kinase blockers were administered 10 min before reperfusion. The infarct-limiting effect of deltorphin II is associated with the activation of PI3K and ERK1/2 and does not depend on JAK2.
Asunto(s)
Daño por Reperfusión Miocárdica , Fosfatidilinositol 3-Quinasas , Ratas , Animales , Masculino , Ratas Wistar , Fosfatidilinositol 3-Quinasas/metabolismo , Sistema de Señalización de MAP Quinasas , Daño por Reperfusión Miocárdica/tratamiento farmacológico , ReperfusiónRESUMEN
Spontaneous bioelectrical activity of the brain and the duration of gasping were recorded in mice during modeling of global strangulation ischemia of the brain against the background of preventive administration of citicoline. The maximum neuroprotective effect of citicoline was observed when it was administered 60 min before the simulation of ischemia and was completely prevented by preliminary administration of a selective P2Y6 receptor antagonist MRS2578. The obtained experimental data attest to the leading role of receptor mechanisms in the implementation of neuroprotective activity of citicoline.
Asunto(s)
Isquemia Encefálica , Fármacos Neuroprotectores , Ratones , Animales , Citidina Difosfato Colina/farmacología , Citidina Difosfato Colina/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , EncéfaloRESUMEN
In male Wistar rats, coronary occlusion (45 min) and reperfusion (120 min) were modeled. Selective δ2-opioid receptor agonist (deltorphin II, 0.12 mg/kg) was administered intravenously 5 min before reperfusion; NO synthase inhibitor (L-NAME, 10 mg/kg), MPT pore blocker (atractyloside, 5 mg/kg), and protein kinase A inhibitor (H-89, 10 µg/kg) were administered intravenously 10 min before reperfusion. Deltorphin II administered before reperfusion led to a 2-fold decrease in the infarct size. The infarct-limiting effect of deltorphin II was associated with blockade of MPT pore. Protein kinase A and NO synthase were not involved in the cardioprotective effect of deltorphin II.
Asunto(s)
Proteínas Quinasas Dependientes de AMP Cíclico , Óxido Nítrico Sintasa , Ratas , Animales , Masculino , Ratas Wistar , Óxido Nítrico Sintasa/metabolismo , Analgésicos Opioides/farmacología , Receptores Opioides/metabolismo , InfartoRESUMEN
We studied the effect of induced metabolic syndrome (MetS) on the effectiveness of the infarct-limiting effect of remote ischemic postconditioning (RP) in Wistar rats. The involvement of leptin and corticosterone in the formation of arterial hypertension (AH) and in reduction of the effectiveness of RP in MetS was also studied. MetS was induced by high-carbohydrate high-fat diet with replacement of drinking water with 20% fructose solution for 90 days. MetS simulation led to obesity, AH, impaired lipid and carbohydrate metabolism, hyperleptinemia, and moderate stress. All animals were subjected to 45-min coronary occlusion and 120-min reperfusion. In the RP groups, tourniquets were applied on the hind limbs in the area of the hip joint immediately after the end of ischemia (3 cycles consisting of 5-min ischemia and 5-min reperfusion). A direct correlation was found between the severity of AH in rats with MetS and the levels of corticosterone and leptin. In rats with MetS, the effectiveness of RP decreased: a direct correlation between the infarct size and serum content of leptin was revealed in rats with MetS+RP. Corticosterone seems to be one of the factors of AH development in rats with MetS.
Asunto(s)
Hipertensión , Poscondicionamiento Isquémico , Síndrome Metabólico , Daño por Reperfusión Miocárdica , Ratas , Animales , Corticosterona , Daño por Reperfusión Miocárdica/metabolismo , Ratas Wistar , Leptina , Isquemia , InfartoRESUMEN
In rats anesthetized with α-chloralose, coronary artery occlusion (45 min) and reperfusion (120 min) were modeled. The selective δ2-opioid receptor agonist deltorphin II was administered 5 min before reperfusion. Protein kinase C inhibitor chelerythrine, AMP-activated protein kinase inhibitor compound C, and ATP-sensitive K+ channel blockers glibenclamide, 5-hydroxydecanoate, and HMR 1098 were administered 10 min before reperfusion. It was found that the infarct-limiting effect of deltorphin II is associated with activation of protein kinase C and opening of sarcolemmal ATP-sensitive K+ channel.
Asunto(s)
Daño por Reperfusión Miocárdica , Proteínas Quinasas Activadas por AMP/metabolismo , Adenosina Trifosfato , Animales , Canales KATP/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Proteína Quinasa C/genética , Proteína Quinasa C/metabolismo , Ratas , Receptores Opioides/metabolismoRESUMEN
The role of opioid kappa1 and kappa2 receptors in reperfusion cardiac injury was studied. Male Wistar rats were subjected to a 45-min coronary artery occlusion followed by a 120-min reperfusion. Opioid kappa receptor agonists were administered intravenously 5 min before the onset of reperfusion, while opioid receptor antagonists were given 10 min before reperfusion. The average value of the infarct size/area at risk (IS/AAR) ratio was 43 - 48% in untreated rats. Administration of the opioid kappa1 receptor agonist (-)-U-50,488 (1 mg/kg) limited the IS/AAR ratio by 42%. Administration of the opioid kappa receptor agonist ICI 199,441 (0.1 mg/kg) limited the IS/AAR ratio by 41%. The non-selective opioid kappa receptor agonist (+)-U-50,488 (1 mg/kg) with low affinity for opioid kappa receptor, the peripherally acting opioid kappa2 receptor agonist ICI 204,448 (4 mg/kg) and the selective opioid ?2 receptor agonist GR89696 (0.1 mg/kg) had no effect on the IS/AAR ratio. Pretreatment with naltrexone, the peripherally acting opioid receptor antagonist naloxone methiodide, or the selective opioid kappa2 receptor antagonist nor-binaltorphimine completely abolished the infarct-reducing effect of (-)-U-50,488 and ICI 199,441. Pretreatment with the selective opioid ? receptor antagonist TIPP[psi] and the selective opioid µ receptor antagonist CTAP did not alter the infarct reducing effect of (-)-U-50,488 and ICI 199,441. Our study is the first to demonstrate the following: (a) the activation of opioid kappa2 receptor has no effect on cardiac tolerance to reperfusion; (b) peripheral opioid kappa1 receptor stimulation prevents reperfusion cardiac injury; (c) ICI 199,441 administration resulted in an infarct-reducing effect at reperfusion; (e) bradycardia induced by opioid kappa receptor antagonists is not dependent on the occupancy of opioid kappa receptor.
Asunto(s)
3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclohexil)-bencenacetamida, (trans)-Isómero/administración & dosificación , Analgésicos Opioides/administración & dosificación , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Pirrolidinas/administración & dosificación , Receptores Opioides kappa/agonistas , 3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclohexil)-bencenacetamida, (trans)-Isómero/toxicidad , Administración Intravenosa , Analgésicos Opioides/toxicidad , Animales , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/fisiopatología , Modelos Animales de Enfermedad , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Antagonistas de Narcóticos/administración & dosificación , Piperazinas/administración & dosificación , Pirrolidinas/toxicidad , Ratas Wistar , Receptores Opioides kappa/metabolismo , Transducción de SeñalRESUMEN
We performed a comparative analysis of infarction-limiting activity of analogues of opioid receptor agonist U-50488 under conditions of heart reperfusion in rats. Derivatives of amide N-methyl-2-(pyrrolidin-1-yl)cyclohexyl-1-amine were administered 5 min before reperfusion in a dose of 1 mg/kg, derivative II (opicor) was additionally used in a dose of 2 mg/kg. In a dose of 1 mg/kg, all derivatives of opioid U-50488 were ineffective and produced no infarction-limiting effect. Opicor in a dose of 2 mg/kg reduced the infarction size/area at risk ratio and improved the contractility parameters of the isolated heart. Opioid receptor antagonist naltrexone (5 mg/kg) abolished the infarction-limiting effect of opicor. Hence, the infarction-reducing effect of opicor is associated with activation of opioid receptors. We also demonstrated that the opioid (opicor) can improve cardiac contractility during the reperfusion period.
Asunto(s)
Amidas/química , Aminas/química , Aminas/uso terapéutico , Analgésicos Opioides/uso terapéutico , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Animales , Cardiotónicos/química , Cardiotónicos/uso terapéutico , Corazón/efectos de los fármacos , Masculino , Antagonistas de Narcóticos/química , Antagonistas de Narcóticos/uso terapéutico , Ratas , Ratas Wistar , Receptores Opioides/metabolismoRESUMEN
A 45-min coronary artery occlusion followed by a 120-min reperfusion was performed in rats anesthetized with α-chloralose. The selective κ1-opioid receptor (OR) agonist U-50,488 was administered intravenously in doses of 0.1 or 1 mg/kg. The selective κ2-OR agonist GR-89696 was injected in a dose of 0.1 mg/kg. The selective κ1-OR agonists ICI-199,441 and ICI-204,448 were employed in the doses of 0.1 and 4 mg/kg, respectively. These drugs were injected 5 min prior to reperfusion. U-50,488 exerted the cardioprotective effect in a dose of 1 mg/kg, but it produced no effect on infarct size in a dose of 0.1 mg/kg. ICI-199,441 reduced the reperfusion injury to the heart. The infarct size limiting effects of U-50,488 and ICI-199,441 were prevented by preliminary injection of naltrexone or nor-binaltorphimine. It is concluded that infarct size limiting effects of U-50,488 and ICI-199,441 were mediated via activation of κ1-OR.
Asunto(s)
Infarto del Miocardio/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Receptores Opioides kappa/metabolismo , Animales , Masculino , Ratas , Ratas WistarRESUMEN
The study examined the effects of δ-opioid receptor (OR) agonists on infarct size on cardiac ischemia (45 min) and reperfusion (120 min) in vivo model in rats narcotized with α-chloralose. The OR agonists were injected intravenously 5 min prior to reperfusion, OR antagonists were administered 10 min before reperfusion. A selective δ-OR agonist BW373U86 (1 mg/kg) reduced the infarct size/area at risk ratio. A selective δ1-OR agonist DPDPE injected in the doses of 0.1 or 0.969 mg/kg produced no effect on infarct size. The selective δ2-OR agonist deltorphin II (0.12 mg/kg) reduced infarct size/area at risk ratio by 2 times. The δ-OR agonist p-Cl-Phe-DPDPE (1 mg/kg) reduced infarct size/area at risk ratio by 40%. Naltrexone and naloxone methiodide, the peripheral OR antagonists, and selective δ2-OR antagonist naltriben prevented the infarct size limiting effect of deltorphin II. Therefore, activation of peripheral δ2-OR enhanced cardiac resistance against toxic action of reperfusion. During reperfusion, deltorphin II demonstrated the most pronounced cardioprotective activity.
Asunto(s)
Cardiotónicos/uso terapéutico , Encefalina D-Penicilamina (2,5)/uso terapéutico , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismo , Antagonistas de Narcóticos/uso terapéutico , Receptores Opioides delta/metabolismo , Animales , Benzamidas/uso terapéutico , Masculino , Piperazinas/uso terapéutico , Ratas , Ratas WistarRESUMEN
Chronic continuous normobaric hypoxia (CNH) increases cardiac tolerance to ischemia/reperfusion injury in vivo and this effect is mediated via µ and delta2 opioid receptors (ORs) activation. CNH has also been shown to be cardioprotective in isolated rat heart. In this study, we hypothesize that this cardioprotective effect of CNH is mediated by activation of µ and delta2 ORs and preservation of mitochondrial function. Hearts from rats adapted to CNH (12 % oxygen) for 3 weeks were extracted, perfused in the Langendorff mode and subjected to 45 min of global ischemia and 30 min of reperfusion. Intervention groups were pretreated for 10 min with antagonists for different OR types: naloxone (300 nmol/l), the selective delta OR antagonist TIPP(psi) (30 nmol/l), the selective delta1 OR antagonist BNTX (1 nmol/l), the selective delta2 OR antagonist naltriben (1 nmol/l), the selective peptide µ OR antagonist CTAP (100 nmol/l) and the selective delta OR antagonist nor-binaltorphimine (3 nmol/l). Creatine kinase activity in coronary effluent and cardiac contractile function were monitored to assess cardiac injury and functional impairment. Additionally, cardiac tissue was collected to measure ATP and to isolate mitochondria to measure respiration rate and calcium retention capacity. Adaptation to CNH decreased myocardial creatine kinase release during reperfusion and improved the postischemic recovery of contractile function. Additionally, CNH improved mitochondrial state 3 and uncoupled respiration rates, ADP/O, mitochondrial transmembrane potential and calcium retention capacity and myocardial ATP level during reperfusion compared to the normoxic group. These protective effects were completely abolished by naloxone, TIPP(psi), naltriben, CTAP but not BNTX or nor-binaltorphimine. These results suggest that cardioprotection associated with adaptation to CNH is mediated by µ and delta2 opioid receptors activation and preservation of mitochondrial function.
Asunto(s)
Hipoxia/fisiopatología , Mitocondrias Cardíacas/fisiología , Daño por Reperfusión Miocárdica/fisiopatología , Receptores Opioides delta/fisiología , Receptores Opioides mu/fisiología , Animales , Masculino , Mitocondrias Cardíacas/efectos de los fármacos , Daño por Reperfusión Miocárdica/prevención & control , Antagonistas de Narcóticos/farmacología , Técnicas de Cultivo de Órganos , Ratas , Ratas Wistar , Receptores Opioides delta/antagonistas & inhibidores , Receptores Opioides mu/antagonistas & inhibidoresRESUMEN
Selective agonist of δ2-opioid receptors deltorphin II and its retroenantio analog (0.12 mg/kg intravenously) were preventively injected to male Wistar rats 15 min prior to 45-min coronary occlusion or 5 min before 120-min reperfusion. Administration of deltorphin II before artery occlusion and before reperfusion decreased the infarct size/area at risk ratio. Deltorphin II prevented the appearance of ischemia-provoked ventricular arrhythmias and exerted no effect on HR and BP (systolic and diastolic). The retroenantio analog of deltorphin II produced no antiarrhythmic or infarct-limiting effects, but reduced HR without affecting BP. Deltorphin II can be viewed as a promising prototype for a medicinal remedy to treat acute myocardial infarction.
Asunto(s)
Analgésicos Opioides/farmacología , Arritmias Cardíacas/tratamiento farmacológico , Cardiotónicos/farmacología , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Oligopéptidos/farmacología , Animales , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatología , Presión Sanguínea/efectos de los fármacos , Trastornos Cerebrovasculares , Vasos Coronarios/cirugía , Frecuencia Cardíaca/efectos de los fármacos , Inyecciones Intravenosas , Masculino , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/fisiopatología , Ratas , Ratas Wistar , Receptores Opioides delta/agonistas , Receptores Opioides delta/metabolismo , EstereoisomerismoRESUMEN
Selective agonists of µ1- and µ2-opioid receptors endomorphin-2 and endomorphin-1 injected intravenously in a dose of 4500 nmol/kg in 5 min before coronary blood flow resumption had no effect on cardiac reperfusion damage. Consequently, µ1- and µ2-opioid receptors are not involved in the regulation of heart tolerance to reperfusion injury. Nonselective opioid receptor agonist ß-endorphin (100 nmol/kg) also did not affect heart tolerance to the pathogenic effect of reperfusion.
Asunto(s)
Analgésicos Opioides/farmacología , Arritmias Cardíacas/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Oligopéptidos/farmacología , betaendorfina/farmacología , Animales , Arritmias Cardíacas/fisiopatología , Presión Sanguínea/efectos de los fármacos , Oclusión Coronaria , Vasos Coronarios/cirugía , Poscondicionamiento Isquémico , Masculino , Daño por Reperfusión Miocárdica/fisiopatología , Miocardio/metabolismo , Miocardio/patología , Ratas , Ratas Wistar , Receptores Opioides mu/agonistas , Receptores Opioides mu/metabolismoRESUMEN
We studied the effects of ß-adrenoceptor antagonists propranolol and nadolol and L-type Ca(2+)-channel blocker verapamil on cardiac reperfusion injury developed after 45-min coronary occlusion. The substances were injected intravenously 5 min before reperfusion. The results indicate that activation of ß-adrenoceptors and opening of L-type Ca(2+)-channels promote the development of cardiac reperfusion injury, while blockage of ß-adrenoceptors and/or L-type Ca(2+)-channels prevents reoxygenation-induced myocardial injury. Propranolol, nadolol, and verapamil can produce infraction-limiting effects after onset of ischemic heart injury.
Asunto(s)
Canales de Calcio Tipo L/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Miocardio/metabolismo , Receptores Adrenérgicos beta/metabolismo , Antagonistas Adrenérgicos beta/farmacología , Animales , Masculino , Nadolol/farmacología , Propranolol/farmacología , Ratas , Verapamilo/farmacologíaRESUMEN
It is known that agonists of adenosine, opioid, and bradykinin receptors mimic the phenomenon of ischemic postconditioning. There is no commonly accepted notion of what adenosine receptor subtypes must be activated to increase cardiac resistance to reperfusion injury. Intravenous infusion of adenosine or intracoronary administration of adenosine produce infarct-limiting effect and contribute to a more complete restoration of coronary blood flow after recanalization of the infarct-related coronary artery. It was confirmed that opioids mimic the phenomenon of postconditioning. According to obtained data, the most promising compounds for the prevention of reperfusion injury of the heart are κ(1)- and δ(2)-opioid receptor agonists, as they produce the infarct-limiting effect, while not reducing the arterial pressure.
Asunto(s)
Circulación Coronaria/efectos de los fármacos , Vasos Coronarios/metabolismo , Poscondicionamiento Isquémico , Miocardio/metabolismo , Agonistas del Receptor Purinérgico P1/uso terapéutico , Receptores de Bradiquinina/agonistas , Receptores Opioides/agonistas , Animales , Vasos Coronarios/patología , Humanos , Miocardio/patología , Receptores de Bradiquinina/metabolismo , Receptores Opioides/metabolismoRESUMEN
The cardiovascular effects of opioid peptides may be associated with activation of opioid receptors located on the sarcolemma of cardiomyocytes, on the cell membrane of ICA and endothelial cells, on sympathetic and parasympathetic nerve terminals in the heart and in the adrenals. The cardiovascular effects of opioids penetrating the blood-brain barrier may be the result of their impact on central opioid receptors.
Asunto(s)
Frecuencia Cardíaca/fisiología , Corazón/inervación , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Péptidos Opioides/metabolismo , Sistema Nervioso Parasimpático/metabolismo , Animales , HumanosRESUMEN
We studied the ability of the agonist of κ1-opioid receptors U-50,488 in doses of 0.1 and 1 mg/kg to simulate ischemic pre- and postconditioning of the heart and κ-opioid receptors ICI 199,441 in a dose of 0.1 mg/kg to simulate the antiarrhythmic effect of heart preconditioning. The duration of ischemia was 10 or 45 min and the duration of reperfusion was 10 min or 2 h. Administration of 1 mg/kg U-50,488 both before ischemia and 5 min before reperfusion produced a pronounced antiarrhythmic effect. U-50,488 injected 5 min before reperfusion 2-fold reduced the ratio of infarction to risk area. Administration of ICI 199,441 in a dose of 0.1 mg/kg 15 min before ischemia produced a potent antiarrhythmic effect. Antiarrhythmic effect of κ-opioid receptor agonists depended on activation of κ-opioid receptors.
Asunto(s)
3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclohexil)-bencenacetamida, (trans)-Isómero/farmacología , Cardiotónicos/farmacología , Precondicionamiento Isquémico Miocárdico/métodos , Daño por Reperfusión Miocárdica/prevención & control , Pirrolidinas/farmacología , Receptores Opioides kappa/agonistas , 3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclohexil)-bencenacetamida, (trans)-Isómero/uso terapéutico , Animales , Antiarrítmicos/farmacología , Antiarrítmicos/uso terapéutico , Cardiotónicos/uso terapéutico , Isquemia Miocárdica/tratamiento farmacológico , Isquemia Miocárdica/patología , Pirrolidinas/uso terapéutico , Ratas , Ratas WistarRESUMEN
MEK, PI3, p38, tyrosine, and mTOR kinases are not involved in the regulation of heart resistance to the arrhythmogenic action of short-term ischemia/reperfusion in non-adapted rats.