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ABSTRACT: In this study, we investigated the cardioprotective effect of acetylcholine (ACh) via modulation of mitochondrial permeability transition pore (MPTP) opening through the mitochondrial ATP-sensitive potassium channel (mitoK(ATP) channel). In isolated ventricular myocytes from male Sprague-Dawley rats, 0.1 micromol/L ACh was administered for 6 min, before 30 min of simulated ischemia and 30 min of reperfusion (I/R). A mitoK(ATP) inhibitor (5-hydroxydecanoate, 5-HD) and an MPTP opener (atractyloside, Atr) were used to analyze the underlying mechanisms. Myocyte contractile function, myocyte viability, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) and mitochondrial membrane potential were assayed. During reperfusion, the amplitudes of contraction, +/-dL/dt(max), and end-diastolic length of myocytes were decreased, which were markedly improved by pretreatment with ACh. However, such effects of ACh were reversed by 100 micromol/L 5-HD for 20 min before ischemia, or 20 micromol/L Atr for 20 min at the beginning of reperfusion. Pretreatment with ACh markedly reduced I/R-induced cell death, LDH release, ROS signals and mitochondrial membrane potential dissipation, all of which were reversed by 5-HD or Atr. In conclusion, ACh may protect ventricular myocytes from I/R injury by inhibiting MPTP opening and stabilizing the mitochondrial membrane potential through activating the mitoK(ATP) channel.
Methods and Findings in Experimental and Clinical Pharmacology 03/2010; 32(2):107-12. · 0.93 Impact Factor
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ABSTRACT: To investigate the chronic cardioprotection of testosterone against ischemia/reperfusion injury and acute effect against H2O2-stress injury.
The vas deferens were ligated bilaterally and the testes removed from male Sprague-Dawley rats, and testosterone propionate was supplemented every day. Eight weeks after gonadectomy, all the hearts were mounted on a Langendorff apparatus to assess the level of lactate dehydrogenase (LDH) in the coronary effluent and the infarct size. Isolated adult ventricular myocytes were obtained by enzymatic dissociation, in which H2O2-stress injury model was copied. The myocyte contraction was determined, and mitochondrial reactive oxygen species (ROS) production was measured by loading with fluorescent probe DCFH-DA.
In gonadectomy model, pretreatment with testosterone propionate significantly decreases the LDH release and the infarct size. In the isolated myocytes model, testosterone attenuated the decreases of +/- dL/dtmax and dL which produced by H2O2-stress, and prevented the production of ROS induced by H2O2-stress. Co-treatment with atractyloside or 5-HD attenuated the effect of testosterone.
The findings show the chronic cardioprotection of testosterone against ischemia/reperfusion injury and acute effect against H2O2-stress injury via opening of mitoK(ATP) channel or/and the inhibiting mitochondrial permeability transition pore.
Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 02/2009; 25(1):31-5.
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ABSTRACT: To investigate the effect of 8-opioid receptors in the cardioprotection elicited by ischemic postconditioning and the underlying mechanism.
The isolated perfused hearts of male Sprague-Dawley rats were subjected to 30 min of global ischemia followed by 120 min of reperfusion. Formazan content of myocardium was measured spectrophotometrically, and the activity of lactate dehydrogenase (LDH) in the coronary effluent was measured. In isolated ventricular myocytes hypoxic postconditioning was achieved by 3 cycles of 5 min reoxygenation/5 min hypoxia starting at the beginning of reoxygenation, and cell viability was measured.
In the Langendorff perfused rat heart model, ischemic postconditioning (6 cycles of 10 s reperfusion/10 s global ischemia starting at the beginning of reperfusion) increased formazan content, reduced LDH release, improved the recovery of the left ventricular developed pressure, maximal rise/fall rate of left ventricular pressure and rate pressure product (left ventricular developed pressure multiplied by heart rate), attenuated the decrease of coronary flow during reperfusion and increased the isolated cell viability. Pretreatment with naltrindole, an antagonist of delta-opioid receptors and calcium-activated potassium channel (KCa) blocker paxilline attenuated the effect of ischemic/hypoxic postconditioning.
The findings indicate that ischemic postconditioning protects myocardium against ischemia/reperfusion injury via activating delta-opioid receptors and opening KCa.
Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 05/2008; 24(2):184-9.
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ABSTRACT: The aim of the present study was to determine whether the effective cardioprotection conferred by puerarin against ischemia and reperfusion is mediated by the calcium-activated potassium channel. Hearts isolated from male Sprague-Dawley rats were perfused on a Langendorff apparatus and subjected to 30 min of global ischemia followed by 120 min of reperfusion. The production of formazan, which provides an index of myocardial viability, was measured by absorbance at 550 nm, and the level of lactate dehydrogenase (LDH) in the coronary effluent was determined. Pretreatment with puerarin at 0.24 mmol/l for 5 min before ischemia increased myocardial formazan content and reduced LDH release during reperfusion. Administration of paxilline (1 micromol/l), an antagonist of the calcium-activated potassium channel, attenuated the protective effects of puerarin. In isolated ventricular myocytes, pretreatment with puerarin prevented simulated ischemia and reperfusion injury, hydrogen peroxide-induced cell death and the release of reactive oxygen species. Paxilline and chelerythrine (a protein kinase C inhibitor) both attenuated the effects of puerarin. These findings indicate that puerarin protects the myocardium against ischemia and reperfusion injury via opening the calcium-activated potassium channel and activating protein kinase C.
European Journal of Pharmacology 12/2007; 574(2-3):179-84. · 2.52 Impact Factor
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ABSTRACT: To explore the cardioprotection effect of co-treatment with ischemic postconditioning and preconditioning in ischemia/reperfusion (I/R) injury and the related mechanism.
Male Sprague-Dawley rats were used for Langendorff isolated heart perfusion. The hearts were subjected to global ischemia for 60 min followed by 120 min of reperfusion. The cardiomyocyte viability was measured by MTT-formazan method, and the cardiac injury was evaluated by the levels of lactate dehydrogenase (LDH) in the coronary effluent. Ventricular hemodynamic parameters were also measured.
In 60 min of ischemia and 120 min of reperfusion group, ischemic postconditioning increased formazan content, reduced LDH release, but hemodynamic parameters did not improved. Co-treatment with ischemic postconditioning and preconditioning during the prolonged ischemia further improved the hemodynamic parameters. The calcium activated potassium channel antagonist paxilline attenuated the effect of co-treatment with ischemic postconditioning and preconditioning.
Ischemic postconditioning and preconditioning may synergically protect myocardium from severe ischemia injury, which may be related to calcium-activated potassium channel.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 02/2007; 36(1):35-40.
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ABSTRACT: To investigate the effect of kappa-Opioid receptors in the cardioprotection elicited by ischemic postconditioning and the underlying mechanism.
The isolated perfused hearts of male Sprague-Dawley rats were subjected to 30 min of global ischemia followed by 120 min of reperfusion. formazan content of myocardium was measured spectrophotometrically, and the level of lactate dehydrogenase (LDH) in the coronary effluent was also measured. In isolated ventricular myocytes hypoxia postconditioning was achieved by 3 cycles of 5 min reoxygenation/5 min hypoxia starting at the beginning of reoxygenation, and cell viability was measured.
In the Langendorff perfused rat heart model, ischemic postconditioning (6 cycles of 10 s reperfusion/10 s global ischemia starting at the beginning of reperfusion) increased formazan content, reduced LDH release, improved the recovery of the left ventricular developed pressure, maximal rise/fall rate of left ventricular pressure, left ventricular end-diastolic pressure and rate pressure product (left ventricular developed pressure multiplied by heart rate), attenuated the decrease of coronary flow during reperfusion and increased the isolated cell viability. Pretreatment with nor-BNI, an antagonist of kappa-Opioid receptors and mitoK(ATP) blocker 5-HD attenuated the effect of ischemic/hypoxic postconditioning.
Postconditioning may protect myocardium against ischemia/reperfusion injury via activating kappa-Opioid receptors and mitoK(KATP).
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 02/2007; 36(1):41-7.
