Intermittent Hypoxia Impairs Endothelial Function in Early Preatherosclerosis

2015 ◽  
pp. 1-7 ◽  
Author(s):  
I. Tuleta ◽  
C. N. França ◽  
D. Wenzel ◽  
B. Fleischmann ◽  
G. Nickenig ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Intermittent Hypoxia

scholarly journals Intermittent hypoxia and arterial blood pressure control in humans: role of the peripheral vasculature and carotid baroreflex

2016 ◽  
Vol 311 (3) ◽  
pp. H699-H706 ◽  
Author(s):  
Joshua C. Tremblay ◽  
Lindsey M. Boulet ◽  
Michael M. Tymko ◽  
Glen E. Foster
Keyword(s):  
Blood Pressure ◽  
Endothelial Function ◽  
Femoral Artery ◽  
Brachial Artery ◽  
Intermittent Hypoxia ◽  
Variable Pressure ◽  
Peripheral Vasculature ◽  
Arterial Blood ◽  
Carotid Baroreflex ◽  
Obstructive Sleep

Intermittent hypoxia (IH) occurs in association with obstructive sleep apnea and likely contributes to the pathogenesis of hypertension. The purpose of this study was to examine the putative early adaptations at the level of the peripheral vasculature and carotid baroreflex (CBR) that may promote the development of hypertension. Ten healthy male participants (26 ± 1 yr, BMI = 24 ± 1 kg/m2) were exposed to 6 h of IH (1-min cycles of normoxia and hypoxia) and SHAM in a single-blinded, counterbalanced crossover study design. Ambulatory blood pressure was measured during each condition and the following night. Vascular strain of the carotid and femoral artery, a measure of localized arterial stiffness, and hemodynamic shear patterns in the brachial and femoral arteries were measured during each condition. Brachial artery reactive hyperemia flow-mediated vasodilation was assessed before and after each condition as a measure of endothelial function. CBR function and its control over leg vascular conductance (LVC) were measured after each condition with a variable-pressure neck chamber. Intermittent hypoxia 1) increased nighttime pulse pressure by 3.2 ± 1.3 mmHg, 2) altered femoral but not brachial artery hemodynamics, 3) did not affect brachial artery endothelial function, 4) reduced vascular strain in the carotid and possibly femoral artery, and 5) shifted CBR mean arterial pressure (MAP) to higher MAP while blunting LVC responses to CBR loading. These results suggest limb-specific vascular impairments, reduced vascular strain, and CBR resetting combined with blunted LVC responses are factors in the early pathogenesis of IH-induced development of hypertension.

scholarly journals Plasma Exosomes and Improvements in Endothelial Function by Angiotensin 2 Type 1 Receptor or Cyclooxygenase 2 Blockade following Intermittent Hypoxia

2017 ◽  
Vol 8 ◽  
Author(s):  
Abdelnaby Khalyfa ◽  
Nina Youssefnia ◽  
Glen E. Foster ◽  
Andrew E. Beaudin ◽  
Zhuanghong Qiao ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Intermittent Hypoxia ◽  
Cyclooxygenase 2

scholarly journals Low but not high frequency of intermittent hypoxia suppresses endothelium-dependent, oxidative stress-mediated contractions in carotid arteries of obese mice

2018 ◽  
Vol 125 (5) ◽  
pp. 1384-1395 ◽  
Author(s):  
Mary Y. K. Lee ◽  
Grace Ge ◽  
M. L. Fung ◽  
Paul M. Vanhoutte ◽  
Judith C. W. Mak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sleep Apnea ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
High Frequency ◽  
Intermittent Hypoxia ◽  
Carotid Arteries ◽  
Low Frequency ◽  
Obese Mice ◽  
Diet Induced Obesity

Obstructive sleep apnea is characterized by intermittent hypoxia (IH) during sleep and predisposes to endothelial dysfunction. Obesity is a major risk factor for the occurrence of sleep apnea. The present study compared the functional impact of low- (IH10; 10 hypoxic events/h) and high-frequency (IH60; 60 hypoxic events/h) IH for 4 wk on endothelial function in male C57BL/6 mice with or without high-fat (HF) diet-induced obesity. Mean arterial blood pressure (tail cuff method) was increased in obese mice after IH60 exposure, i.e., HF + IH60 group. The serum levels of the oxidative stress marker malondialdehyde were augmented in lean IH60 and HF groups, with a further increase in HF + IH60 but a reduction in HF + IH10 mice compared with the HF group. Vascular responsiveness was assessed as changes in isometric tension in isolated arteries. Relaxations to the endothelium-dependent vasodilator acetylcholine were impaired in HF + IH60 aortae. Endothelium-dependent contractions (EDC; response to acetylcholine in the presence of the nitric oxide synthase inhibitor l-NAME) in carotid arteries were augmented in the HF group, but this HF-induced augmentation was suppressed by low-frequency IH exposure. The addition of apocynin (antioxidant) reduced EDC in HF and HF + IH60 groups but not in HF + IH10 group. In conclusion, these findings suggest that exposure of obese mice to mild IH exerts preconditioning-like suppression of endothelium-dependent and oxidative stress-mediated contractions. When IH severity increases, this suppression diminishes and endothelial dysfunction accelerates. NEW & NOTEWORTHY The present study demonstrates, for the first time, that low-frequency intermittent hypoxia may exert a preconditioning-like suppression of oxidative stress-induced endothelium-dependent contractions in mice with diet-induced obesity. This relative suppression was diminished as intermittent hypoxia became more severe, and a deleterious effect on endothelial function emerged.

scholarly journals Alpha Lipoic Acid Improves Endothelial Function and Oxidative Stress in Mice Exposed to Chronic Intermittent Hypoxia

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Mohammad Badran ◽  
Bisher Abuyassin ◽  
Saeid Golbidi ◽  
Najib Ayas ◽  
Ismail Laher
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Alpha Lipoic Acid ◽  
Systemic Oxidative Stress ◽  
Enos Uncoupling ◽  
And Oxidative Stress

Objective. Obstructive sleep apnea (OSA) is characterized by recurrent airway collapse that causes chronic intermittent hypoxia (CIH). OSA is associated with systemic inflammation and oxidative stress resulting in endothelial dysfunction and cardiovascular disease (CVD). Alpha lipoic acid (ALA) is a potent antioxidant with anti-inflammatory properties. We hypothesized that dietary ALA can improve endothelial function of mice exposed to CIH. Methods. Mice were exposed to either CIH or intermittent air (IA) and treated with dietary ALA (0.2% w/w) or a regular chow diet for 8 weeks. Endothelial function, endothelial nitric oxide (eNOS) uncoupling, systemic oxidative stress, systemic inflammation, aortic expression of inflammatory cytokines, and antioxidant enzymes were measured after 8 weeks. Results. Mice exposed to CIH exhibited endothelial dysfunction accompanied by systemic oxidative stress and inflammation as well as increased aortic expression of inflammatory cytokines. Furthermore, CIH led to eNOS uncoupling. Treatment with dietary ALA reversed endothelial dysfunction in mice exposed to CIH, lowered systemic oxidative stress and inflammation, prevented the increases of inflammatory cytokine gene expression, increased the expression of antioxidant enzymes, and preserved eNOS in a coupled state. Conclusion. ALA attenuates endothelial dysfunction by preventing oxidative stress and inflammation and restoring nitric oxide bioavailability in mice exposed to CIH. Our data suggests the potential beneficial use of ALA as adjunctive therapy in OSA.

scholarly journals Chronic intermittent hypoxia accelerates coronary microcirculatory dysfunction in insulin-resistant Goto-Kakizaki rats

2016 ◽  
Vol 311 (2) ◽  
pp. R426-R439 ◽  
Author(s):  
Yi Ching Chen ◽  
Tadakatsu Inagaki ◽  
Yutaka Fujii ◽  
Daryl O. Schwenke ◽  
Hirotsugu Tsuchimochi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endothelial Function ◽  
Intermittent Hypoxia ◽  
Wistar Rats ◽  
Chronic Intermittent Hypoxia ◽  
Vascular Endothelial ◽  
Gk Rats ◽  
Insulin Resistant ◽  
Coronary Endothelial Function

Chronic intermittent hypoxia (IH) induces oxidative stress and inflammation, which impair vascular endothelial function. Long-term insulin resistance also leads to endothelial dysfunction. We determined, in vivo, whether the effects of chronic IH and insulin resistance on endothelial function augment each other. Male 12-wk-old Goto-Kakizaki (GK) and Wistar control rats were subjected to normoxia or chronic IH (90-s N2, 5% O2 at nadir, 90-s air, 20 cycles/h, 8 h/day) for 4 wk. Coronary endothelial function was assessed using microangiography with synchrotron radiation. Imaging was performed at baseline, during infusion of acetylcholine (ACh, 5 μg·kg−1·min−1) and then sodium nitroprusside (SNP, 5 μg·kg−1·min−1), after blockade of both nitric oxide (NO) synthase (NOS) with Nω-nitro-l-arginine methyl ester (l-NAME, 50 mg/kg) and cyclooxygenase (COX, meclofenamate, 3 mg/kg), and during subsequent ACh. In GK rats, coronary vasodilatation in response to ACh and SNP was blunted compared with Wistar rats, and responses to ACh were abolished after blockade. In Wistar rats, IH blunted the ability of ACh or SNP to increase the number of visible vessels. In GK rats exposed to IH, neither ACh nor SNP were able to increase visible vessel number or caliber, and blockade resulted in marked vasoconstriction. Our findings indicate that IH augments the deleterious effects of insulin resistance on coronary endothelial function. They appear to increase the dependence of the coronary microcirculation on NO and/or vasodilator prostanoids, and greatly blunt the residual vasodilation in response to ACh after blockade of NOS/COX, presumably mediated by endothelium-derived hyperpolarizing factors.

scholarly journals Extracellular vesicle microRNA cargoes from intermittent hypoxia-exposed cardiomyocytes and their effect on endothelium

2020 ◽  
Author(s):  
Yu Li ◽  
Huina Zhang ◽  
Yunhui Du ◽  
Lu Peng ◽  
Yanwen Qin ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Western Blotting ◽  
Intermittent Hypoxia ◽  
Extracellular Vesicle ◽  
Differentially Expressed ◽  
Functional Study ◽  
Western Blotting Analysis ◽  
Mirna Array ◽  
Blotting Analysis ◽  
Obstructive Sleep

Abstract Background Intermittent hypoxia (IH), as the crucial pathophysiological feature of obstructive sleep apnea syndrome (OSAS), is an independent risk factor initiating the progression of cardiovascular complications. However, how IH cause cardiovascular injury and initiate inter-organ communication remains unclear. Extracellular vesicle (EV) are reported to be involved in cell-to-cell and organ-to-organ communications through selectively carrying RNA and protein cargos from donor cells and delivering them to recipient cells. By utilizing an unbiased miRNA microarray approach, current study attempted to determine whether IH may alter miRNA profiles in cardiomyocyte-derived extracellular vesicles and whether EVs from IH-treated cardiomyocytes could affect endothelial function. Methods EVs were isolated from culture medium of normoxia- or intermittent hypoxia-treated C57BL/6 mouse primary cardiomyocytes. miRNA array assay was used to identify myocardial EV miRNA. The expression of target miRNAs was validated by qPCR and the enriched function of the target miRNAs were predicted by bioinformatics and western blotting analysis. Moreover, vascular functional study validated whether EVs from IH-exposed cardiomyocytes could influence endothelial function. Results 63 differentially expressed miRNAs, including 32 up-regulated and 31 down-regulated miRNAs were identified in EVs from IH-exposed cardiomyocytes. Among them, 16 miRNAs with homologous sequence in mouse and human were selected and verified by qPCR assay and 11 miRNAs were proved with the same tendency as miRNA array identified. KEGG pathway and western blotting analysis showed the main enriched pathway of differentially expressed miRNA was associated with PI3K/Akt signaling pathway. Of note, EVs from IH-exposed cardiomyocytes dramatically impaired endothelium-dependent relaxation and inhibited Akt/eNOS pathway in endothelial cells. Conclusions This study provides the first evidence that IH causes significant alteration in myocardial EV miRNA composition, which may contribute to IH or OSAS-triggered cardiovascular injury and organ-to-organ communication.

scholarly journals Effects of chronic intermittent hypoxia on endothelial function in mice

2006 ◽  
Vol 20 (5) ◽  
Author(s):  
Jordan Daniel Miller ◽  
Donald D Lund ◽  
Donald D Heistad
Keyword(s):  
Endothelial Function ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia

scholarly journals Restoring leptin signaling reduces hyperlipidemia and improves vascular stiffness induced by chronic intermittent hypoxia

2011 ◽  
Vol 300 (4) ◽  
pp. H1467-H1476 ◽  
Author(s):  
Ronghua Yang ◽  
Gautam Sikka ◽  
Jill Larson ◽  
Vabren L. Watts ◽  
Xiaolin Niu ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Intermittent Hypoxia ◽  
Cardiac Myocyte ◽  
Vascular Stiffness ◽  
Chronic Intermittent Hypoxia ◽  
Leptin Signaling ◽  
Vascular Abnormalities ◽  
Vascular Compliance ◽  
Obstructive Sleep ◽  
Relaxation Responses

Chronic intermittent hypoxia (IH) during sleep can result from obstructive sleep apnea (OSA), a disorder that is particularly prevalent in obesity. OSA is associated with high levels of circulating leptin, cardiovascular dysfunction, and dyslipidemia. Relationships between leptin and cardiovascular function in OSA and chronic IH are poorly understood. We exposed lean wild-type (WT) and obese leptin-deficient ob/ob mice to IH for 4 wk, with and without leptin infusion, and measured cardiovascular indices including aortic vascular stiffness, endothelial function, cardiac myocyte morphology, and contractile properties. At baseline, ob/ob mice had decreased vascular compliance and endothelial function vs. WT mice. We found that 4 wk of IH decreased vascular compliance and endothelial relaxation responses to acetylcholine in both WT and leptin-deficient ob/ob animals. Recombinant leptin infusion in both strains restored IH-induced vascular abnormalities toward normoxic WT levels. Cardiac myocyte morphology and function were unaltered by IH. Serum cholesterol and triglyceride levels were significantly decreased by leptin treatment in IH mice, as was hepatic stearoyl-Coenzyme A desaturase 1 expression. Taken together, these data suggest that restoring normal leptin signaling can reduce vascular stiffness, increase endothelial relaxation, and correct dyslipidemia associated with IH.

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