ABSTRACT
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.
Subject(s)
Heart/drug effects , Narcotic Antagonists/pharmacology , Opioid Peptides/metabolism , Stress, Physiological/drug effects , Animals , Male , Naltrexone/analogs & derivatives , Naltrexone/pharmacology , Quaternary Ammonium Compounds/pharmacology , Rats , Rats, Wistar , Receptors, Opioid/metabolismABSTRACT
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.
Subject(s)
Hypoxia/physiopathology , Myocardial Infarction/metabolism , Myocardial Infarction/physiopathology , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/physiopathology , Potassium Channels/metabolism , Animals , Blood Pressure/drug effects , Decanoic Acids/therapeutic use , Glyburide/therapeutic use , Heart Rate/drug effects , Hydroxy Acids/therapeutic use , Male , Myocardial Infarction/drug therapy , Potassium Channel Blockers/therapeutic use , Rats , Rats, WistarABSTRACT
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.
Subject(s)
Analgesics, Opioid/pharmacology , Arrhythmias, Cardiac/drug therapy , Cardiotonic Agents/pharmacology , Myocardial Reperfusion Injury/drug therapy , Oligopeptides/pharmacology , Animals , Arrhythmias, Cardiac/metabolism , Arrhythmias, Cardiac/physiopathology , Blood Pressure/drug effects , Cerebrovascular Disorders , Coronary Vessels/surgery , Heart Rate/drug effects , Injections, Intravenous , Male , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/physiopathology , Rats , Rats, Wistar , Receptors, Opioid, delta/agonists , Receptors, Opioid, delta/metabolism , StereoisomerismABSTRACT
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.
Subject(s)
Acclimatization/physiology , Cold Temperature , Cold-Shock Response/physiology , Corticosterone/blood , Hydrocortisone/blood , Viscera/physiology , Animals , Male , Organ Size/physiology , Rats , Rats, WistarABSTRACT
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.
