Effects of mitochondrial KATP modulators on cardioprotection induced by chronic high altitude hypoxia in rats

Neckář, Jan; Szárszoi, Ondřej; Koten, Lukás; Papoušek, F; Ošťádal, B; Grover, Gary J.; Kolář, František

doi:10.1016/s0008-6363(02)00456-x

Cited by 83 publications

(59 citation statements)

References 36 publications

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“…These results are in agreement with those of Neckar et al [11], who demonstrated that long term intermittent hypoxia corresponding to 5000 m for 8 h/ day, 5 days a week, for 24-32 days, increased the tolerance of rat hearts to ischemia/reperfusion. This was determined as improved recovery of post-ischemic contractile function and reduction in infarct size.…”

Section: Discussionsupporting

confidence: 93%

“…Previous investigators have shown that intermittent hypoxia could protect against ischemia/ reperfusion injury [4][5][6]11], but no measure of apoptosis has been reported. Another finding in our study is that the antiapoptotic effect of intermittent hypoxia was due to regulate expression of Bcl-2/Bax protein.…”

Section: Discussionmentioning

confidence: 99%

“…Many studies showed that intermittent hypoxia might have the cardioprotective effects similar to those observed in ischemic preconditioning [2][3][4][5][6][7][8]. A number of studies have attempted to define the mechanisms of this phenomenon and several potential factors have been proposed to be involved in the protective mechanism afforded by intermittent hypoxia [3,[5][6][7][9][10][11], however, the precise mechanisms underlying the protective effects of intermittent hypoxia on ischemic hearts are far from clear.…”

Section: Introductionmentioning

confidence: 99%

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Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2/Bax expression

et al. 2003

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Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury. Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to investigate whether intermittent hypoxia could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. Adult male Sprague-Dawley rats were exposed to hypoxia simulated 5000 m in a hypobaric chamber for 6 h/day, lasting 42 days. Normoxia group rats were kept under normoxic conditions. Isolated perfused hearts from both groups were subjected to 30 min of global ischemia followed by 60 min reperfusion. Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA agarose gel electrophoresis. Expressions of apoptosis related proteins, Bax and Bcl-2, in cytosolic and membrane fraction were detected by Western Blotting. After ischemia/reperfusion, enhanced recovery of cardiac function was observed in intermittent hypoxia hearts compared with normoxia group. Ischemia/ reperfusion-induced apoptosis, as evidenced by TUNEL-positive nuclei and DNA fragmentation, was significantly reduced in intermittent hypoxia group compared with normoxia group. After ischemia/reperfusion, expression of Bax in both cytosolic and membrane fractions was decreased in intermittent hypoxia hearts compared with normoxia group. Although ischemia/reperfusion did not induce changes in the level of Bcl-2 expression in cytosolic fraction between intermittent hypoxia and normoxia groups, the expression of Bcl-2 in membrane fraction was upregulated in intermittent hypoxia group compared with normoxia group. These results indicated that the cardioprotection of intermittent hypoxia against ischemia/reperfusion injury appears to be in part due to reduce myocardial apoptosis. Intermittent hypoxia attenuated ischemia/reperfusion-induced apoptosis via increasing the ratio of Bcl-2/Bax, especially in membrane fraction.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2/Bax expression

et al. 2003

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“…In addition to modulating Ca 2ϩ -handling pathways, the cardioprotective effects of IH have been independently attributed to mechanisms leading to opening of plasma and/or mitochondrial membrane K ATP channels (153,255,274,275). Adult and neonatal rats exhibited diminished frequency of ischemia-induced, K ATP channel-dependent arrhythmias, smaller infarct size and better postischemic contractility recovery following IH exposure (12,153,161).…”

Section: Circulatory Systemmentioning

confidence: 99%

Hypoxia. 4. Hypoxia and ion channel function

Shimoda

Polàk

2011

American Journal of Physiology-Cell Physiology

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The ability to sense and respond to oxygen deprivation is required for survival; thus, understanding the mechanisms by which changes in oxygen are linked to cell viability and function is of great importance. Ion channels play a critical role in regulating cell function in a wide variety of biological processes, including neuronal transmission, control of ventilation, cardiac contractility, and control of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium channels in chemoreceptors, the effect of hypoxia on an assortment of ion channels has been studied in an array of cell types. In this review, we describe the effects of both acute and sustained hypoxia (continuous and intermittent) on mammalian ion channels in several tissues, the mode of action, and their contribution to diverse cellular processes. oxygen deprivation; mammalian ion channels; oxygen homeostasis SENSING and appropriately responding to changes in O 2 concentration is of paramount importance for the survival of all organisms. Over time, O 2 homeostasis has evolved into a complex system to regulate O 2 delivery and use. While the rapid response to acute reductions in O 2 concentration typically results from processes that alter preexisting proteins, such as phosphorylation, stabilization, dimerization, or degradation, durable adaptation to prolonged hypoxic insult requires a coordinated response at the level of gene transcription. Since a deficit in O 2 is an important component of various physiological processes and the pathogenesis of numerous diseases, understanding the mechanisms by which changes in O 2 are linked to cell function is of great interest.Ion channels play a critical role in regulating a wide variety of biological processes, including neuronal transmission; control of ventillation; contraction of cardiac, skeletal, and smooth muscle; transport of nutrients and ions across the epithelium; T-cell activation; and glucose metabolism and pancreatic ␤-cell insulin release. To date, over 300 types of ion channels, differing in their mode of activation (voltage-dependent or -independent, ligand-gated, mechanosensitive, pH) and their ionic permeability (K ϩ , Ca 2ϩ , Cl Ϫ , Na ϩ ), have been identified. This heterogeneity in ion channel populations provides an astonishing array of variable responses within and between cell types. In 1988, a report demonstrating that rabbit carotid body glomus cells express an O 2 -sensitive potassium channel ushered in a new era of research exploring whether ion channel activity could be regulated in response to changes in O 2 availability (131). Since that initial description of an O 2 -regulated ion channel, an abundance of work has been produced indicating that a variety of ion channels spread across the different ion channel families are O 2 sensitive and exhibit changes in channel activity with acute hypoxia and alterations in channel quantity with prolonged hypoxic challenge. Although a great amount of work has been devoted to the study of hypoxia and ion channels in reptiles, amp...

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“…An epidemiological study reported that men residing at high altitude resulted in protection against death from ischemic heart disease [34]. The epidemiological observations on the cardioprotective effect of high altitude were confirmed in various experimental models [35][36][37]. It has been reported that the hearts of animals adapted to long-term HAH develop better functional recovery following ischemia and produce smaller cardiac infarction.…”

Section: Cardiac Systemmentioning

confidence: 89%

Cardiovascular Adaptation to High-Altitude Hypoxia

Ji¹,

Wang²,

Xiao³

2017

Hypoxia and Human Diseases

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High-altitude exposure has been well recognized as a hypoxia exposure that significantly affects cardiovascular function. However, the pathophysiologic adaptation of cardiovascular system to high-altitude hypoxia (HAH) varies remarkably. It may depend on the exposed time and oxygen partial pressure in the altitude place. In short-term HAH, cardiovascular adaptation is mainly characterized by functional alteration, including cardiac functional adjustments, pulmonary vascular constriction, transient pulmonary hypertension, and changes in cerebral blood flow (CBF). These changes may be explained mainly by ventilatory acclimatization and variation of autonomic nervous activity. In long-term HAH, cardiovascular adaptation is mainly characterized by both functional and structural alterations. These changes include right ventricle (RV) hypertrophy, persistent pulmonary hypertension, lower CBF and reduced uteroplacental and fetal volumetric blood flows.

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Effects of mitochondrial KATP modulators on cardioprotection induced by chronic high altitude hypoxia in rats

Abstract: The results suggest that opening of mitochondrial K(ATP) channels is involved in the cardioprotective mechanism conferred by long-term adaptation to intermittent high altitude hypoxia.

Cited by 83 publications

References 36 publications

Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2/Bax expression

Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2/Bax expression

Hypoxia. 4. Hypoxia and ion channel function

Cardiovascular Adaptation to High-Altitude Hypoxia

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