Detection of endogenous acetylcholine release during brief ischemia in the rabbit ventricle: A possible trigger for ischemic preconditioning

Kawada, Toru; Akiyama, Tsuyoshi; Shimizu, Shuji; Kamiya, Atsunori; Uemura, Kazunori; Li, Meihua; Shirai, Masamitsu; Sugimachi, Masaru

doi:10.1016/j.lfs.2009.08.015

Cited by 29 publications

(24 citation statements)

References 28 publications

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“…While several studies from Krieg et al demonstrated exogenous ACh could induce cardioprotection in the Langendorff model, the same group discounts its involvement in the mechanism of IPC [38–40]. However, two studies from Kawada et al demonstrated brief, 5-min ischaemia in in vivo rabbit and cat models induces interstitial release of ACh in the ventricles [35, 36]. Data from our study confirm those of Kawada et al with a significant release of ACh observed in coronary effluent following IPC.…”

Section: Discussionmentioning

confidence: 99%

Intrinsic cardiac ganglia and acetylcholine are important in the mechanism of ischaemic preconditioning

et al. 2017

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This study aimed to investigate the role of the intrinsic cardiac nervous system in the mechanism of classical myocardial ischaemic preconditioning (IPC). Isolated perfused rat hearts were subjected to 35-min regional ischaemia and 60-min reperfusion. IPC was induced as three cycles of 5-min global ischaemia–reperfusion, and provided significant reduction in infarct size (IS/AAR = 14 ± 2% vs control IS/AAR = 48 ± 3%, p < 0.05). Treatment with the ganglionic antagonist, hexamethonium (50 μM), blocked IPC protection (IS/AAR = 37 ± 7%, p < 0.05 vs IPC). Moreover, the muscarinic antagonist, atropine (100 nM), also abrogated IPC-mediated protection (IS/AAR = 40 ± 3%, p < 0.05 vs IPC). This indicates that intrinsic cardiac ganglia remain intact in the Langendorff preparation and are important in the mechanism of IPC. In a second group of experiments, coronary effluent collected following IPC, from ex vivo perfused rat hearts, provided significant cardioprotection when perfused through a naïve isolated rat heart prior to induction of regional ischaemia–reperfusion injury (IRI) (IS/ARR = 19 ± 2, p < 0.05 vs control effluent). This protection was also abrogated by treating the naïve heart with hexamethonium, indicating the humoral trigger of IPC induces protection via an intrinsic neuronal mechanism (IS/AAR = 46 ± 5%, p < 0.05 vs IPC effluent). In addition, a large release in ACh was observed in coronary effluent was observed following IPC (IPCeff = 0.36 ± 0.03 μM vs C eff = 0.04 ± 0.04 μM, n = 4, p < 0.001). Interestingly, however, IPC effluent was not able to significantly protect isolated cardiomyocytes from simulated ischaemia–reperfusion injury (cell death = 45 ± 6%, p = 0.09 vs control effluent). In conclusion, IPC involves activation of the intrinsic cardiac nervous system, leading to release of ACh in the ventricles and induction of protection via activation of muscarinic receptors.

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Section: Discussionmentioning

confidence: 99%

Intrinsic cardiac ganglia and acetylcholine are important in the mechanism of ischaemic preconditioning

et al. 2017

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“…40 Using a microdialysis technique, Kawada et al demonstrated that acetylcholine level in the rabbit left ventricle induced by vagal stimulation is at the nanomolar level. 41 In the synaptic space after quantal release, the amount of acetylcholine can reach the millimolar range. 42,43 Moreover, the concentration of by guest on May 11, 2018 http://atvb.ahajournals.org/ Downloaded from acetylcholine for therapy in the pathological conditions is usually higher than the physiological level.…”

Section: Discussionmentioning

confidence: 99%

Reduction of Mitochondria–Endoplasmic Reticulum Interactions by Acetylcholine Protects Human Umbilical Vein Endothelial Cells From Hypoxia/Reoxygenation Injury

et al. 2015

ATVB

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Objective-We explored the role of endoplasmic reticulum (ER)-mitochondria Ca 2+ cross talk involving voltage-dependent anion channel-1 (VDAC1)/glucose-regulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex and mitofusin 2 in endothelial cells during hypoxia/reoxygenation (H/R), and investigated the protective effects of acetylcholine. Approach and Results-Acetylcholine treatment during reoxygenation prevented intracellular and mitochondrial Ca 2+ increases and alleviated ER Ca 2+ depletion during H/R in human umbilical vein endothelial cells. Consequently, acetylcholine enhanced mitochondrial membrane potential and inhibited proapoptotic cascades, thereby reducing cell death and preserving endothelial ultrastructure. This effect was likely mediated by the type-3 muscarinic acetylcholine receptor and the phosphatidylinositol 3-kinase/Akt pathway. In addition, interactions among members of the VDAC1/ glucose-regulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex were increased after H/R and were associated with mitochondrial Ca 2+ overload and cell death. Inhibition of the partner of the Ca 2+ channeling complex (VDAC1 siRNA) or a reduction in ER-mitochondria tethering (mitofusin 2 siRNA) prevented the increased protein interaction within the complex and reduced mitochondrial Ca 2+ accumulation and subsequent endothelial cell death after H/R. Intriguingly, acetylcholine could modulate ER-mitochondria Ca 2+ cross talk by inhibiting the VDAC1/glucoseregulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex and mitofusin 2 expression. Phosphatidylinositol 3-kinase siRNA diminished acetylcholine-mediated inhibition of mitochondrial Ca 2+ overload and VDAC1/glucoseregulated protein 75/inositol 1,4,5-trisphosphate receptor 1 complex formation induced by H/R. Conclusions-Our data suggest that ER-mitochondria interplay plays an important role in reperfusion injury in the endothelium and may be a novel molecular target for endothelial protection. Acetylcholine attenuates both intracellular and mitochondrial Ca 2+ overload and protects endothelial cells from H/R injury, presumably by disrupting the ER-mitochondria interaction.

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“…Because of the involvement of multiple factors in lung IR injury, it has been difficult to achieve an obvious pulmonary protection by targeting any one single factor. Recent studies have shown that stimulating vagus nerve generated a protective effect in myocardial IR injury [4,5]. The protective role of sensory neurons in renal and liver IR injury have also been documented [6][7][8].…”

Section: Introductionmentioning

confidence: 96%

TRPV1 Agonist Capsaicin Attenuates Lung Ischemia-Reperfusion Injury in Rabbits

Wang

et al. 2012

Journal of Surgical Research

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Detection of endogenous acetylcholine release during brief ischemia in the rabbit ventricle: A possible trigger for ischemic preconditioning

Cited by 29 publications

References 28 publications

Intrinsic cardiac ganglia and acetylcholine are important in the mechanism of ischaemic preconditioning

Intrinsic cardiac ganglia and acetylcholine are important in the mechanism of ischaemic preconditioning

Reduction of Mitochondria–Endoplasmic Reticulum Interactions by Acetylcholine Protects Human Umbilical Vein Endothelial Cells From Hypoxia/Reoxygenation Injury

TRPV1 Agonist Capsaicin Attenuates Lung Ischemia-Reperfusion Injury in Rabbits

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