RESUMO
In Wistar rats, stress was modeled by 24-h immobilization in a supine posture and stress-induced damage to the heart was assessed by accumulation of 99mTc-pyrophosphate in the myocardium. The intensity of stress reaction was measured by serum levels of cortisol and insulin. Both stressinduced damage to the heart and intensity of stress reaction were examined under control conditions and in rats treated with opioid receptor antagonists naltrexone, methylnaltrexone bromide, MR2266, and ICI174.864. Activation of central µ-opioid receptors with endogenous opioids aggravated stress-induced cardiomyopathy, while stimulation of peripheral µ-opioid receptors produced a cardioprotective effect. The stress-induced damage to the heart was not directly related to up-regulation of cortisol secretion in response to 24-h immobilization. Blockade of the central opioid receptors promoted a decrease in cortisol level in stressed rats.
Assuntos
Coração/efeitos dos fármacos , Antagonistas de Entorpecentes/farmacologia , Peptídeos Opioides/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Animais , Masculino , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Compostos de Amônio Quaternário/farmacologia , Ratos , Ratos Wistar , Receptores Opioides/metabolismoRESUMO
The role of KATP channels in myocardial infarct size-limiting effect of chronic continuous normobaric hypoxia was examined in a rat model based on a 20-min coronary occlusion and subsequent 3-h reperfusion. Rats were adapted to normobaric hypoxia (12% O2) for 21 days. This hypoxia produced a pronounced infarct size-limiting effect, which had been prevented by 0.3 mg/kg glibenclamide, a non-selective inhibitor of entire pool of KATP channels, or 5 mg/kg 5-hydroxydecanoate, an inhibitor of mitochondrial KATP channels. The study highlighted the important role of mitochondrial KATP channels in myocardial infarct size-limiting effect of chronic normobaric hypoxia.
Assuntos
Hipóxia/fisiopatologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Canais de Potássio/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Ácidos Decanoicos/uso terapêutico , Glibureto/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Hidroxiácidos/uso terapêutico , Masculino , Infarto do Miocárdio/tratamento farmacológico , Bloqueadores dos Canais de Potássio/uso terapêutico , Ratos , Ratos WistarRESUMO
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.
Assuntos
Analgésicos Opioides/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Cardiotônicos/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Oligopeptídeos/farmacologia , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Transtornos Cerebrovasculares , Vasos Coronários/cirurgia , Frequência Cardíaca/efeitos dos fármacos , Injeções Intravenosas , Masculino , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Ratos , Ratos Wistar , Receptores Opioides delta/agonistas , Receptores Opioides delta/metabolismo , EstereoisomerismoRESUMO
Permanent exposure of rats to four-week cold treatment at +4ºC for 24 h/day resulted in increased weights of the brown adipose tissue, adrenals, and spleen and had no effect on the levels of cortisol and corticosterone in the blood serum. Similar data were observed after exposure of rats to intermittent four-week cold treatment at +4ºC for 8 h/day. After short-term exposure of rats to intermittent cold treatment at +4ºC for 1.5 h/day, all indices studied were similar to those observed in intact animals.
Assuntos
Aclimatação/fisiologia , Temperatura Baixa , Resposta ao Choque Frio/fisiologia , Corticosterona/sangue , Hidrocortisona/sangue , Vísceras/fisiologia , Animais , Masculino , Tamanho do Órgão/fisiologia , Ratos , Ratos WistarRESUMO
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.