The effect of the chronic and acute antioxidant tempol (superoxide dismutase mimetic) treatment on cardiac ischemic tolerance was investigated in adult male Wistar rats. The first experimental group was given tempol (1 mM) in drinking water for three weeks, the second group received tempol (100 mg/kg, i.v.) 10 min before test ischemia, and control rats received the same volume of solvent. Anesthetized open-chest animals (pentobarbitone 60 mg/kg, i.p.) were subjected to 20-min coronary artery occlusion and 3-h reperfusion for infarct size determination. Ventricular arrhythmias were monitored during ischemia and at the beginning (5 min) of reperfusion. Acute tempol administration shifted the time profile of ischemic arrhythmias to the later phase and significantly increased the number of ischemic and reperfusion premature ventricular complexes, respectively (504±127 and 84±21) as compared with the chronically treated group (218±36 and 47±7) or controls (197±26 and 31±7). Acute tempol-treated rats exhibited a tendency to decrease infarct size (P = 0.087). The mechanism of proarrhythmic tempol action during ischemia and reperfusion remains to be elucidated.

• Klíčová slova
• Ischemia/eperfusion, Arrhythmias, Infarction, Oxygen radicals, Tempol,
• MeSH
• antioxidancia metabolismus   škodlivé účinky   MeSH
• cyklické N-oxidy škodlivé účinky   MeSH
• financování organizované MeSH
• infarkt myokardu patologie   MeSH
• ischemická choroba srdeční patofyziologie   MeSH
• krevní tlak fyziologie   MeSH
• krysa rodu rattus MeSH
• peroxid vodíku metabolismus   MeSH
• reperfuzní poškození myokardu patofyziologie   MeSH
• spinové značení MeSH
• srdeční arytmie patofyziologie   MeSH
• srdeční frekvence fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

Adaptation to chronic intermittent hypoxia (CIH) is associated with reactive oxygen species (ROS) generation implicated in the improved cardiac tolerance against acute ischemia-reperfusion injury. Phospholipases A2 (PLA2s) play an important role in cardiomyocyte phospholipid metabolism influencing membrane homeostasis. Here we aimed to determine the effect of CIH (7000 m, 8 h/day, 5 weeks) on the expression of cytosolic PLA2 (cPLA2α), its phosphorylated form (p-cPLA2α), calcium-independent (iPLA2), and secretory (sPLA2IIA) at protein and mRNA levels, as well as fatty acids (FA) profile in left ventricular myocardium of adult male Wistar rats. Chronic administration of antioxidant tempol was used to verify the ROS involvement in CIH effect on PLA2s expression and phospholipid FA remodeling. While CIH did not affect PLA2s mRNA levels, it increased the total cPLA2α protein in cytosol and membranes (by 191% and 38%, respectively) and p-cPLA2α (by 23%) in membranes. On the contrary, both iPLA2 and sPLA2IIA were downregulated by CIH. CIH further decreased phospholipid n-6 polyunsaturated FA (PUFA) and increased n-3 PUFA proportion. Tempol treatment prevented only CIH-induced cPLA2α up-regulation and its phosphorylation on Ser505. Our results show that CIH diversely affect myocardial PLA2s and suggest that ROS are responsible for the activation of cPLA2α under these conditions.

• MeSH
• antioxidancia farmakologie   MeSH
• chronická nemoc MeSH
• cyklické N-oxidy farmakologie   MeSH
• fosfolipasy A2, skupina IV genetika   metabolismus   MeSH
• fosforylace účinky léků   MeSH
• hypoxie enzymologie   metabolismus   MeSH
• krysa rodu rattus MeSH
• mastné kyseliny metabolismus   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• regulace genové exprese enzymů účinky léků   MeSH
• spinové značení MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Hypoxic pulmonary vasoconstriction (HPV), an important physiological mechanism, is regulated by changes in the production of and interactions among reactive oxygen species (ROS). There is controversy, however, over whether HPV is mediated by an increase or a decrease in ROS production. Also, the role of NO in HPV remains unclear. The aim of this study was to investigate whether the inhibition of HPV by the antioxidant tempol was dependent on the concentration of NO, and how its effect was influenced by increased basal pulmonary vascular tone. In isolated rat lungs, we measured vasoconstrictor responses to acute ventilatory hypoxia before and after administration of tempol during perfusion with or without L-NAME. We found that tempol abolished HPV independently of NO production. When we increased basal vascular tone by K(+)-induced depolarization, we also found that tempol completely inhibited HPV. Our results indicate that inhibition of HPV by the superoxide dismutase mimetic tempol does not depend on either NO production or a decrease in basal vascular tone.

• MeSH
• antioxidancia farmakologie   MeSH
• cyklické N-oxidy farmakologie   MeSH
• financování organizované MeSH
• hypoxie farmakoterapie   metabolismus   MeSH
• inhibitory enzymů farmakologie   MeSH
• krysa rodu rattus MeSH
• NG-nitroargininmethylester farmakologie   MeSH
• oxid dusnatý metabolismus   MeSH
• plicní oběh fyziologie   účinky léků   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• spinové značení MeSH
• superoxiddismutasa metabolismus   MeSH
• vazokonstrikce fyziologie   účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

• Klíčová slova
• TEMPOL,
• MeSH
• merkaptopurin farmakologie   toxicita   MeSH
• myši MeSH
• oxid dusičitý MeSH
• protinádorové látky MeSH
• systém (enzymů) cytochromů P-450 účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH

• Publikační typ
• abstrakty MeSH

BACKGROUND: Lungs retrieved from non-heart-beating donors (NHBDs) may alleviate the shortage of suitable organs for transplantation. The critical point is the preservation of lungs during warm ischemia, when severe damage is caused by free radicals. We investigated the effect of ventilation, pre-arrest administration of heparin, and the cell-permeable free radical scavenger, tempol, on the function of NHBD grafts. METHODS: Six experimental and two control groups (n = 6 per group) were established. All experimental groups underwent a protocol of NHBD lung harvesting, which included 1 hour of warm ischemia after pentobarbital euthanasia followed by 90 minutes of cold ischemia. The groups were constructed as follows: Group An-non-ventilated during warm ischemia, no heparin; Group Av-room-air ventilated during warm ischemia, no heparin; Group Hn-non-ventilated, heparin added pre-arrest; Group Hv-ventilated, heparin; Group Tn-non-ventilated, heparin and tempol added pre-arrest; Group Tv-ventilated, tempol, heparin; Group Ac-control group, no warm and cold ischemia, lungs harvested immediately after euthanasia; and Group Tc-controls with tempol added pre-arrest. The lungs were then perfused ex vivo and the perfusion pressure, lung weight and arteriovenous difference in oxygen partial pressure were measured. RESULTS: We found that room-air ventilation during warm ischemia caused severe pulmonary edema during reperfusion. Heparinization prevented an increase in perfusion pressure and ameliorated the oxygen transport ability. Pre-arrest administration of tempol prevented edema formation after ventilation during warm ischemia and had a positive effect on the oxygen transport ability of the lungs. CONCLUSIONS: The free radical scavenger tempol, which has a very good ability to permeate biologic membranes, contributes to better preservation of lungs retrieved from NHBDs.

• MeSH
• antikoagulancia farmakologie   MeSH
• časové faktory MeSH
• cyklické N-oxidy farmakologie   MeSH
• dárci tkání MeSH
• financování organizované MeSH
• heparin MeSH
• krysa rodu rattus MeSH
• plíce fyziologie   účinky léků   MeSH
• plicní ventilace MeSH
• reperfuzní poškození prevence a kontrola   MeSH
• scavengery volných radikálů farmakologie   MeSH
• spinové značení MeSH
• srdeční zástava MeSH
• teplá ischemie škodlivé účinky   MeSH
• transplantace plic MeSH
• uchovávání orgánů metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH

• MeSH
• financování organizované MeSH
• Publikační typ
• abstrakty MeSH

• Publikační typ
• abstrakt z konference MeSH

• MeSH
• antioxidancia farmakologie   terapeutické užití   MeSH
• bakteriální infekce farmakoterapie   metabolismus   patologie   MeSH
• cyklické N-oxidy farmakologie   terapeutické užití   MeSH
• finanční podpora výzkumu jako téma MeSH
• hemokoagulace účinky léků   MeSH
• játra metabolismus   účinky léků   MeSH
• krevní tlak účinky záření   MeSH
• oxidační stres účinky záření   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

Obstructive sleep apnea (OSA) has been demonstrated to be implicated in disorder of insulin secretion and diabetes mellitus. In this study, we aimed to evaluate the protective role of tempol, a powerful antioxidant, in chronic intermittent hypoxia (IH)-induced pancreatic injury. The rat model of OSA was established by IH exposure. The pathological changes, increased blood-glucose level, and raised proinsulin/insulin ratio in pancreatic tissues of rats received IH were effectively relieved by tempol delivery. In addition, the enhanced levels of pro-inflammatory cytokines, TNF-alpha, IL-1beta, IL-6, and inflammatory mediators, PGE2, cyclooxygenase-2 (COX-2), NO, and inducible nitric oxide synthase (iNOS) in pancreatic tissue were suppressed by tempol. Moreover, tempol inhibited IH-induced apoptosis in pancreatic tissue as evidenced by upregulated Bcl-2 level, and downregulated Bax and cleaved caspase-3 levels. Finally, the abnormal activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling pathways induced by IH was restrained by tempol administration. In summary, our study demonstrates that tempol relieves IH-induced pancreatic injury by inhibiting inflammatory response and apoptosis, which provides theoretical basis for tempol as an effective treatment for OSA-induced pancreatic injury.

• MeSH
• antioxidancia farmakologie   terapeutické užití   MeSH
• apoptóza účinky léků   fyziologie   MeSH
• cyklické N-oxidy farmakologie   terapeutické užití   MeSH
• hypoxie farmakoterapie   metabolismus   patologie   MeSH
• krysa rodu rattus MeSH
• mediátory zánětu antagonisté a inhibitory   metabolismus   MeSH
• obstrukční spánková apnoe farmakoterapie   metabolismus   patologie   MeSH
• pankreas účinky léků   metabolismus   patologie   MeSH
• potkani Wistar MeSH
• spinové značení MeSH
• zánět farmakoterapie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH