scholarly journals Effect of superoxide anion scavenger on rat hearts with chronic intermittent hypoxia

2016 ◽  
Vol 120 (8) ◽  
pp. 982-990 ◽  
Author(s):  
Peiying Pai ◽  
Ching Jung Lai ◽  
Ching-Yuang Lin ◽  
Yi-Fan Liou ◽  
Chih-Yang Huang ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Superoxide Anion ◽  
Intermittent Hypoxia ◽  
Caspase 3 ◽  
Fas Ligand ◽  
Left Ventricular ◽  
Chronic Intermittent Hypoxia ◽  
Apoptotic Pathway ◽  
Hypoxia Exposure ◽  
Survival Pathway

Only very limited information regarding the protective effects of the superoxide anion scavenger on chronic intermittent hypoxia-induced cardiac apoptosis is available. The purpose of this study is to evaluate the effects of the superoxide anion scavenger on cardiac apoptotic and prosurvival pathways in rats with sleep apnea. Forty-two Sprague-Dawley rats were divided into three groups, rats with normoxic exposure (Control, 21% O2, 1 mo), rats with chronic intermittent hypoxia exposure (Hypoxia, 3-7% O2 vs. 21% O2 per 40 s cycle, 8 h per day, 1 mo), and rats with pretreatment of the superoxide anion scavenger and chronic intermittent hypoxia exposure (Hypoxia-O2−-Scavenger, MnTMPyP pentachloride, 1 mg/kg ip per day; 3–7% O2 vs. 21% O2 per 40 s cycle, 8 h per day, 1 mo) at 5–6 mo of age. After 1 mo, the protein levels and apoptotic cells of excised hearts from three groups were measured by Western blotting and terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay. The superoxide anion scavenger decreased hypoxia-induced myocardial architecture abnormalities, left ventricular hypertrophy, and TUNEL-positive apoptosis. The superoxide anion scavenger decreased hypoxia-induced Fas ligand, Fas death receptors, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fas-dependent apoptotic pathway) as well as Bad, activated caspase-9 and activated caspase-3 (mitochondria-dependent apoptotic pathway), endonuclease G (EndoG), apoptosis-inducing factor (AIF), and TUNEL-positive apoptosis. The superoxide anion scavenger increased IGF-1, IGF-1R, p-PI3k, p-Akt, p-Bad, Bcl-2, and Bcl-xL (survival pathway). Our findings imply that the superoxide anion scavenger might prevent cardiac Fas-mediated and mitochondrial-mediated apoptosis and enhance the IGF-1-related survival pathway in chronic intermittent hypoxia. The superoxide anion scavenger may prevent chronic sleep apnea-enhanced cardiac apoptotic pathways and enhances cardiac survival pathways.

scholarly journals Intermittent hypoxia in utero damages postnatal growth and cardiovascular function in rats

2018 ◽  
Vol 124 (4) ◽  
pp. 821-830 ◽  
Author(s):  
Ling Chen ◽  
Zahra Heidari Zadi ◽  
Jin Zhang ◽  
Steven M. Scharf ◽  
Eung-Kwon Pae
Keyword(s):  
Blood Pressure ◽  
Obstructive Sleep Apnea ◽  
Body Weight ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Cardiovascular Function ◽  
Left Ventricular ◽  
Chronic Intermittent Hypoxia ◽  
Tibial Length ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) is common in pregnancy and may compromise fetal and even postnatal development. We developed an animal model to determine if maternal OSA could have lasting effects in offspring. Pregnant Sprague-Dawley rats were exposed to reduced ambient O2 from 21 to 4–5%, approximately once per minute [chronic intermittent hypoxia (CIH)] for 8 h/day during gestation days 3–19. Similarly handled animals exposed to ambient air served as controls (HC). Offspring were studied for body growth and cardiovascular function for 8 postnatal weeks. Compared with HC, prenatal CIH led to growth restriction, indicated by smaller body weight and tibial length, and higher arterial blood pressure in both male and female offspring. Compared with same-sex HC, CIH males showed abdominal obesity (greater ratio of abdominal fat weight to body weight or tibial length), left ventricular (LV) hypertrophy (greater heart weight-to-tibial length ratio and LV posterior wall diastolic thickness), elevated LV contractility (increases in LV ejection fraction, end-systolic pressure-volume relations, and preload recruitable stroke work), elevated LV and arterial stiffness (increased end-diastolic pressure-volume relationship and arterial elasticity), and LV oxidative stress (greater lipid peroxide content). Compared with female CIH offspring, male CIH offspring had more profound changes in blood pressure (BP), cardiac function, myocardial lipid peroxidase (LPO) content, and abdominal adiposity. Rodent prenatal CIH exposure, mimicking human maternal OSA, exerts detrimental morphological and cardiovascular effects on developing offspring; the model may provide useful insights of OSA effects in humans. NEW & NOTEWORTHY Obstructive sleep apnea is common in human pregnancy. Following maternal exposure to chronic intermittent hypoxia, a hallmark of sleep apnea, both sexes of rat offspring showed growth retardation, with males being more vulnerable to hypertension and dysfunctional left ventricular changes. This model is useful to study detrimental effects of maternal obstructive sleep apnea on developing offspring in humans.

scholarly journals Rats selectively bred for differences in aerobic capacity have similar hypertensive responses to chronic intermittent hypoxia

2013 ◽  
Vol 305 (3) ◽  
pp. H403-H409 ◽  
Author(s):  
Amanda L. Sharpe ◽  
Mary Ann Andrade ◽  
Myrna Herrera-Rosales ◽  
Steven L. Britton ◽  
Lauren G. Koch ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Aerobic Capacity ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Neurogenic Hypertension ◽  
Body Weights ◽  
Aerobic Exercise Capacity ◽  
Chemical Inhibition ◽  
Ganglionic Transmission ◽  
Selection Of

Exposure to chronic intermittent hypoxia (CIH) is an animal model that mimics the repetitive bouts of hypoxemia experienced by humans with sleep apnea. Rats exposed to CIH develop hypertension that depends on the activation of sympathetic nerve activity (SNA). Since obesity and metabolic syndrome have been linked to neurogenic hypertension and sleep apnea, and because sleep apnea can adversely affect aerobic exercise capacity, we tested the hypothesis that rats bred for selection of low aerobic capacity running (LCR) would have a greater hypertensive response to CIH than rats bred for high aerobic capacity running (HCR). Blockade of ganglionic transmission was performed to compare the contribution of SNA to the maintenance of resting mean arterial pressure (MAP). Next, hypertensive responses to 7 days of CIH were compared across LCR and HCR rats (14–16 mo old). Finally, the contribution of the hypothalamic paraventricular nucleus (PVN) to the maintenance of SNA and hypertension after CIH was determined and compared across groups. Although LCR rats were less active and had greater body weights than HCR rats, resting MAP, the contribution of ongoing SNA to the maintenance of MAP, and hypertensive responses to CIH were similar between groups. Contrary to our hypothesis, chemical inhibition of the PVN with muscimol (1 mmol/100 nl) caused a larger fall of MAP in HCR rats than in LCR rats. We conclude that LCR rats do not have resting hypertension or an exaggerated hypertensive response to CIH. Interestingly, the maintenance of CIH hypertension in LCR rats compared with HCR rats appears less reliant on ongoing PVN neuronal activity.

Role of angiotensin II in chronic intermittent hypoxia-induced hypertension and cognitive decline

2021 ◽  
Vol 320 (4) ◽  
pp. R519-R525
Author(s):  
Alexandria B. Marciante ◽  
Brent Shell ◽  
George E. Farmer ◽  
J. Thomas Cunningham
Keyword(s):  
Sleep Apnea ◽  
Cognitive Decline ◽  
Intermittent Hypoxia ◽  
Renin Angiotensin System ◽  
Common Mechanism ◽  
Chronic Intermittent Hypoxia ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Increase Risk ◽  
Subsequent Activation

Sleep apnea is characterized by momentary interruptions in normal respiration and leads to periods of decreased oxygen, or intermittent hypoxia. Chronic intermittent hypoxia is a model of the hypoxemia associated with sleep apnea and results in a sustained hypertension that is maintained during normoxia. Adaptations of the carotid body and activation of the renin-angiotensin system may contribute to the development of hypertension associated with chronic intermittent hypoxia. The subsequent activation of the brain renin-angiotensin system may produce changes in sympathetic regulatory neural networks that support the maintenance of the hypertension associated with intermittent hypoxia. Hypertension and sleep apnea not only increase risk for cardiovascular disease but are also risk factors for cognitive decline and Alzheimer’s disease. Activation of the angiotensin system could be a common mechanism that links these disorders.

scholarly journals Activation of caspase-3 may not contribute to postresuscitation myocardial dysfunction

2009 ◽  
Vol 296 (4) ◽  
pp. H1164-H1174 ◽  
Author(s):  
Jeejabai Radhakrishnan ◽  
Iyad M. Ayoub ◽  
Raúl J. Gazmuri
Keyword(s):  
Cytochrome C ◽  
Dna Fragmentation ◽  
Rat Model ◽  
Caspase 3 ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Stroke Work ◽  
Protective Effects ◽  
Apoptotic Pathway ◽  
Apoptosis Protein

We have previously reported that postresuscitation myocardial dysfunction is accompanied by the release of cytochrome c and caspase-3 activation. We now investigated the role of caspase-3 activation by examining whether such process prompts apoptotic DNA fragmentation, whether caspase-3 inhibition attenuates myocardial dysfunction, and whether myocardial protective effects of sodium-hydrogen exchanger isoform-1 (NHE-1) inhibition involve caspase-3 inhibition using a rat model of ventricular fibrillation (VF) of closed-chest resuscitation. Resuscitation after 4 or 8 min of untreated VF caused significant reductions in left ventricular stroke work index averaging 23% of sham control rats at 4 h postresuscitation. Left ventricular dysfunction was accompanied by increases in cytosolic cytochrome c, decreases in pro- and cleaved caspase-9 fragments, increases in 17-kDa caspase-3 fragments, and increases in caspase-3 activity indicating the activation of the mitochondrial apoptotic pathway but without evidence of apoptotic DNA fragmentation. In addition, levels of heat shock protein 70 were increased and levels of X-linked inhibitor of apoptosis protein and αβ-crystallin were preserved, all of which can exert antiapoptotic effects. In a separate series, the caspase-3 inhibitor z-Asp-Glu-Val-Asp chloromethyl ketone given before the induction of VF failed to prevent postresuscitation myocardial dysfunction despite reductions in caspase-3 activity (2.3 ± 0.5 vs. 1.3 ± 0.5 pmol fluorophore AFC released·mg protein−1·min−1; P < 0.03). Treatment with the NHE-1 inhibitor cariporide had no effect on caspase-3 activity. Accordingly, in this rat model of VF and severe postresuscitation myocardial dysfunction, activation of caspase-3 did not lead to DNA fragmentation or contribute to myocardial dysfunction. Concomitant activation of intrinsic antiapoptotic mechanisms could play a protective role downstream to caspase-3 activation.

Left ventricular function and remodelling in rats exposed stepwise up to extreme chronic intermittent hypoxia

2020 ◽  
Vol 282 ◽  
pp. 103526
Author(s):  
František Papoušek ◽  
David Sedmera ◽  
Jan Neckář ◽  
Bohuslav Ošťádal ◽  
František Kolář
Keyword(s):  
Left Ventricular Function ◽  
Ventricular Function ◽  
Intermittent Hypoxia ◽  
Left Ventricular ◽  
Chronic Intermittent Hypoxia
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