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Hirofumi Nishida Toshiaki Sato Takehiko Ogura Haruaki Nakaya 《Journal of pharmacological sciences》2009,109(3):341-347
Mitochondrial ATP-sensitive K+ (mitoKATP) and Ca2+-activated K+ (mitoKCa) channels exist in cardiac myocytes, and they play key roles in cardioprotection. We have recently reported that K+ influx through mitoKATP or mitoKCa channels occurs independently of each other and confers cardioprotection in a similar manner. Activation of mitoKATP channel is augmented by protein kinase C (PKC), whereas mitoKCa channel is activated by protein kinase A (PKA). However, phosphatidylinositol 3-kinase (PI3-K) is linked to neither mitoKATP nor mitoKCa channels. We have demonstrated that bioactive substances modulate the opening of mitoKATP channels via a PKC-dependent pathway or opening of mitoKCa channels via a PKA-dependent pathway and thereby protecting the heart from ischemia/reperfusion injury. Several endogenous substances such as adenosine and bradykinin can reduce infarct size by activation of mitoKATP channels in a PKC-dependent manner. Adrenomedullin, a potent vasodilator peptide, potentiates the opening of mitoKCa channels by PKA activation. Treatment with adrenomedullin prior to ischemia results in the reduction of infarct size via a PKA-mediated activation of mitoKCa channels. Thus, some endogenous substances confer cardioprotection via PKA- or PKC-mediated activation of mitoKATP or mitoKCa channels. 相似文献
43.
Ashish Kumar Sharma Kunal Kishore Divya Sharma B.P Srinivasan Shyam Sunder Agarwal Ashok Sharma Santosh Kumar Singh Samir Gaur Vijay Singh Jatav 《南京医科大学学报(英文版)》2011,(4):280-286
The present study investigated the antiarrhythmic activity of alcoholic extract of Tinospora cordifolia (T.cordifolia) in CaCl 2 induced arrhythmia.CaCl 2 (25 mg/kg) was administered by intravenous infusion (iv) to produce arrhythmia in rats.The animals were then treated with T.cordifolia extract (150,250,and 450 mg/kg) and verapamil (5 mg/kg,iv).Lead II electrocardiogram was monitored.Plasma calcium,sodium and potassium levels were measured.In CaCl 2 induced arrhythmia,heart rate was decreased by 41.10%,T.... 相似文献
44.
Dai Li Xiao-Jie Zhang Lei Chen Zhichun Yang Han-Wu Deng June Peng Yuan-Jian Li 《Clinical and experimental pharmacology & physiology》2009,36(7):662-667
- 1 It has been shown that calcitonin gene‐related peptide (CGRP) plays an important role in mediating the cardioprotection exerted by rutaecarpine in normal animals. The aim of the present study was to determine whether rutaecarpine is able to decrease the susceptibility of hypertensive animals to ischaemia–reperfusion injury by stimulating CGRP release.
- 2 Spontaneously hypertensive rats (SHR) were pretreated with rutaecarpine (20 or 40 mg/kg per day, i.g.) for 18 days and then the heart and thoracic aorta were isolated for cardiac function and vascular relaxation analysis. Blood samples and coronary effluent were collected to measure CGRP levels and creatine kinase activity, respectively. The effect of 10 or 30 µmol/L rutaecarpine on CGRP release was also examined in isolated aortic rings set up in a homeothermal organ bath.
- 3 Rutaecarpine treatment resulted in a hypotensive effect in SHR concomitant with increases in plasma CGRP levels. In addition, rutaecarpine significantly stimulated the release of CGRP from aortic rings. Twenty minutes ischaemia and 30 min reperfusion resulted in a marked decrease in myocardial function and a significant increase in the release of creatine kinase in normal control (Wistar‐Kyoto) rats, an effect that was exacerbated in SHR. Similarly, the decreased vasodilator response to acetylcholine (3 ? 10?9 to 10?6 mol/L) in isolated aortic rings from Wistar‐Kyoto rats was also aggravated in SHR. Both cardiac function and vasodilator responses were significantly improved in SHR after pretreatment with rutaecarpine.
- 4 The results of the present study suggest that the increased cardiac susceptibility to ischaemia–reperfusion injury in SHR is related to decreased plasma CGRP levels and that antihypertensive therapy with rutaecarpine reverses cardiac susceptibility to reperfusion injury by stimulating CGRP release.
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Classical ischaemic preconditioning, delayed or second window preconditioning and postconditioning are forms of cardioprotection that are dependent on cell surface receptors, intracellular signalling molecules and kinases that ultimately block formation of the mitochondrial permeability transition. The latter is presumed to cause myocardial necrosis as well as apoptosis, so prevention of its formation upon resumption of perfusion after a prolonged coronary occlusion should be cardioprotective. In all of these forms of cardioprotection, formation of cGMP and activation of protein kinase G (PKG) are recognized to be key steps in the signal transduction pathway. Burley et al. highlight the roles of cGMP and PKG in their comprehensive review. They describe the basic biology of PKG and emphasize its compartmentalization, which may be responsible for the frustration induced by assays for PKG in whole cell lysates and for the spurious conclusions about the role of PKG in cardioprotection. This review will be useful to both the novice and the seasoned investigator. 相似文献
47.
Sevoflurane-induced cardioprotection depends on PKC-alpha activation via production of reactive oxygen species 总被引:1,自引:0,他引:1
Bouwman RA Musters RJ van Beek-Harmsen BJ de Lange JJ Lamberts RR Loer SA Boer C 《British journal of anaesthesia》2007,99(5):639-645
BACKGROUND: We previously demonstrated the involvement of the Ca2+-independent protein kinase C-delta (PKC-delta) isoform in sevoflurane-induced cardioprotection against ischaemia and reperfusion (I/R) injury. Since sevoflurane is known to modulate myocardial Ca2+-handling directly, in this study we investigated the role of the Ca2+-dependent PKC-alpha isoform in sevoflurane-induced cardioprotective signalling in relation to reactive oxygen species (ROS), adenosine triphosphate-sensitive mitochondrial K+ (mitoK+(ATP)) channels, and PKC-delta. METHODS: Preconditioned (15 min 3.8 vol% sevoflurane) isolated rat right ventricular trabeculae were subjected to I/R, consisting of 40 min superfusion with hypoxic, glucose-free buffer, followed by normoxic glucose-containing buffer for 60 min. After reperfusion, contractile recovery was expressed as percentage of force development before I/R. The role of PKC-alpha, ROS, mitoK+(ATP) channels, and PKC-delta was established using the following pharmacological inhibitors: Go6976 (GO; 50 nM), n-(2-mercaptopropionyl)-glycine (MPG; 300 microM), 5-hydroxydecanoic acid sodium (5HD; 100 microM), and rottlerin (ROT; 1 microM). RESULTS: Preconditioning of trabeculae with sevoflurane improved contractile recovery after I/R [65 (3)% (I/R + SEVO) vs 47 (3)% (I/R); n = 8; P < 0.05]. This cardioprotective effect was attenuated in trabeculae treated with GO [42 (4)% (I/R + SEVO + GO); P > 0.05 vs (I/R)]. In sevoflurane-treated trabeculae, PKC-alpha translocated towards mitochondria, as shown by immunofluorescent co-localization analysis. GO and MPG, but not 5HD or ROT, abolished this translocation. CONCLUSIONS: Sevoflurane improves post-ischaemic contractile recovery via activation of PKC-alpha. ROS production, but not opening of mitoK+(ATP) channels, precedes PKC-alpha translocation towards mitochondria. This study shows the involvement of Ca2+-dependent PKC-alpha in addition to the well-established role of Ca2+-independent PKC isoforms in sevoflurane-induced cardioprotection. 相似文献
48.
新型NO供体SP/W-5186在兔心肌缺血/再灌注损伤中的作用和机制 总被引:3,自引:0,他引:3
目的:研究一种结构中含有半胱氨酸的新型一氧化氮供体SP/W=-5186,在新西兰兔缺血/再灌注心肌损伤中的作用和机制。方法:兔缺血45min继之再灌注180min。再灌注前5min,通过静脉单剂量给予低剂量(0.3μmol/kg)或高剂量(1μmol/kg)的SP/W05186。结果:给予0.3μjol/kgWP/W0-5186对平均动脉压、心率等心功能指标没有影响,可显著地降低血小板聚集,减少白 相似文献
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50.
Danina M. Muntean Valentin Ordodi René Ferrera Denis Angoulvant 《Fundamental & clinical pharmacology》2013,27(1):21-34
Volatile anaesthetics emerged as important cardioprotective agents in both animal models of ischaemia/reperfusion injury and humans with coronary artery disease. Their administration before a prolonged ischaemic episode is known as anaesthetic preconditioning, whereas when given at the very onset of reperfusion, the strategy is termed anaesthetic postconditioning. Both types of anaesthetic conditioning reduce, albeit not to the same degree, the extent of myocardial injury. They share similar, albeit not identical, intracellular signal transduction pathways with their widely investigated counterparts, ischaemic pre‐ and postconditioning. Despite a wealth of preclinical evidence for cardioprotection for anaesthetic conditioning strategies, their translation into clinical therapy has been rather disappointing. This review highlights the major findings on the cardioprotective effects of volatile anaesthetics in experimental settings. It explores hypotheses that may explain the lack of efficacy observed in several past clinical studies paving the way for future preclinical and translational studies. 相似文献