Intermittent Hypobaric Hypoxia Research Articles

Chronic intermittent hypobaric hypoxia ameliorates vascular reactivity through upregulating adiponectin expression of PVAT in metabolic syndrome rats

Cumulating evidence demonstrated that chronic intermittent hypobaric hypoxia (CIHH) had beneficial effects on the body. This study investigated the role of perivascular adipose tissue (PVAT) in ameliorating effect of CIHH on vascular reactivity by adiponectin in mesenteric artery of metabolic syndrome (MS) rats. Main methods: 6-week-old male Sprague-Dawley rats were randomly divided into four groups: control (CON), MS model, CIHH treatment, and MS+CIHH treatment group. The size of adipocytes in PVAT was measured by scanning electron microscopy. Serum adiponectin was measured. The microvessel recording technique was used to observe the effect of CIHH on contraction and relaxation in mesenteric artery rings. Also, the expressions of interleukin-1β, tumor necrosis factor-α, adiponectin, AdipoR1, AdipoR2, APPL1, and endothelial nitric oxide synthase (eNOS) were assayed by Western blotting. Key findings: in MS rats, adipocyte size increased, serum adiponectin decreased, contraction reaction increased while relaxation reaction decreased, the expression of pro-inflammatory cytokines was upregulated, while adiponectin was downregulated in PVAT, and the expressions of AdipoR1, AdipoR2, APPL, and phosphorylated-eNOS were downregulated in mesenteric artery. All aforementioned abnormalities of MS were ameliorated in MS+CIHH rats. We concluded that CIHH treatment improves vascular reactivity through upregulating adiponectin expression and downregulating pro-inflammatory cytokine expression of PVAT in MS rats.

Citrus tangerine pith extract alleviates hypoxia-induced ileum damage in mice by modulating intestinal microbiota.

Visitors to high altitude are susceptible to hypoxia-induced acute intestinal mucosal barrier injury and severe gastrointestinal disorders, which are life-threatening. Citrus tangerine pith extract (CTPE) is rich in pectin and flavonoids and has been proved to enhance intestinal health and improve gut dysbiosis. In this study, we aim to explore the protective effect of CTPE on ileum injury induced by intermittent hypobaric hypoxia in a mouse model. Balb/c mice were divided into blank normoxia (BN), blank hypobaric hypoxia (BH), hypobaric hypoxia plus CTPE (TH), and hypobaric hypoxia plus Rhodiola extract (RH) groups. From the 6th day of gavage, mice in BH, TH, and RH groups were transferred into a hypobaric chamber at a simulated elevation of 6000 m for 8 hours per day for 10 days. Then half the mice were tested for small intestine movement, and others were used to evaluate intestinal physical barrier function, inflammation, and gut microbiota. Results showed that CTPE reversed the increase of intestinal peristalsis, effectively attenuated impaired structural integrity of ileum, improved the mRNA and protein expression levels of tight junction proteins, and reduced serum D-LA content in mice to alleviate hypoxia-induced mucosal barrier damage. Moreover, CTPE supplementation ameliorated hypoxia-induced intestinal inflammation response by significantly downregulating the proinflammatory cytokines IL-6, TNF-α and IFN-γ. By 16S rDNA gene sequencing of gut microbiota, CTPE significantly increased the abundance of probiotic Lactobacillus, suggesting that CTPE may be used as a prebiotic to regulate ecology of intestinal microorganisms. In addition, Spearman rank correlation analysis revealed that changed gut microbiota were significantly correlated with alteration of intestinal barrier function indexes. Taken together, these results indicate that CTPE effectively alleviates hypoxia-induced intestinal injury in mice and enhances intestinal integrity and barrier function by altering intestinal microbiota composition.

The role of NMDA glutamate receptors in lung injury caused by chronic long-term intermittent hypobaric hypoxia

Chronic intermittent hypoxia (CIH), a component of sleep apnea-hypopnea syndrome, is suggested to cause damage to lung tissue, and the role of glutamate is not well studied. We used a chronic long-term intermittent hypobaric hypoxia (CLTIHH) model of rats to find out if such procedure causes lung injury and the potential effect of N-methyl-D-aspartate receptors (NMDARs) by using receptor antagonist MK-801 (dizocilpine). Thirty-two rats were placed into four groups; a control and three CLTIHH groups where rats were placed into a low-pressure chamber set to 430 mmHg for 5 h/day, 5 days/week, for 5 weeks. Only one group received MK-801 (0.3 mg/kg, ip) daily. We evaluated tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nuclear factor (NF)-kB for the inflammatory process, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), total antioxidant status (TAS), and total oxidant status (TOS) for oxidative stress, and caspase-9 levels. Blood plasma, bronchoalveolar fluid (BALF), and lung tissue extracts were evaluated. Both oxidant and inflammatory parameters were significantly increased in all the mediums of the CLTIHH groups except the group that received MK-801. Significant evidence was collected on MK-801 alleviating the effect of CLTIHH. Histological evaluations revealed lung damage and fibrotic changes in the CLTIHH groups. It was first shown that the CLTIHH procedure caused chronic lung injury, and that inflammation and oxidant stress were influential in the formation of lung injury. Secondly, NMDAR antagonist MK-801 effectively inhibited the development of lung injury and fibrosis.

Malondialdehyde and carbonyl levels in skeletal muscle tissues after intermittent hypobaric hypoxia exposures

Background: Hypobaric hypoxia is a state of decreased oxygen pressure at high altitudes that can lead to hypoxia and oxidative stress as a result. Skeletal muscle is one of the important organs that can be affected by oxidative stress and cause contractile dysfunction.
 Objective: This study aimed to evaluate the impact of intermittent hypobaric hypoxia on oxidative stress markers in rat skeletal muscle, by measuring malondialdehyde (MDA) and carbonyl levels.
 Methods: Twenty-five Wistar rats were allocated into five groups, including one control group and four hypoxic groups (I-IV). The hypoxic groups were exposed to an altitude of 25,000 feet for 5 minutes using hypobaric chamber in once (I), twice (II), three (III), and four (IV) times, with a 7-day interval period between exposures. The control group remained in normobaric conditions throughout the study. MDA levels were measured by thiobarbituric acid (TBA) test, while carbonyl levels were measured using 2,4-dinitrophenylhydrazine (DNPH) reagent.
 Results: The MDA level was significantly increased in group I compared to the control group (p=0.008). There were decreasing MDA levels in groups II, III, and IV compared to group I. The carbonyl level was significantly higher in group I than the control group (p=0.000), with an even higher level observed in group II. Although the carbonyl levels tended to decrease in groups III and IV, they still remained higher than those of the control group.
 Conclusion: Exposure to hypobaric hypoxia leads to an increase in MDA and carbonyl levels in the skeletal muscles, indicating an elevation of oxidative stress levels. However, the subsequent intermittent hypobaric hypoxia exposure resulted in a reduction in these levels, implying that skeletal muscles may adapt to hypoxic conditions.

Cardioprotective Antioxidant and Anti-Inflammatory Mechanisms Induced by Intermittent Hypobaric Hypoxia.

More than 80 million people live and work (in a chronic or intermittent form) above 2500 masl, and 35 million live in the Andean Mountains. Furthermore, in Chile, it is estimated that 100,000 people work in high-altitude shifts, where stays in the lowlands are interspersed with working visits in the highlands. Acute exposure to high altitude has been shown to induce oxidative stress in healthy human lowlanders due to increased free radical formation and decreased antioxidant capacity. However, intermittent hypoxia (IH) induces preconditioning in animal models, generating cardioprotection. Here, we aim to describe the responses of a cardiac function to four cycles of intermittent hypobaric hypoxia (IHH) in a rat model. The twelve adult Wistar rats were randomly divided into two equal groups, a four-cycle of IHH and a normobaric hypoxic control. Intermittent hypoxia was induced in a hypobaric chamber in four continuous cycles (1 cycle = 4 days of hypoxia + 4 days of normoxia), reaching a barometric pressure equivalent to 4600 m of altitude (428 Torr). At the end of the fourth cycle, cardiac structural and functional variables were also determined by echocardiography; furthermore, cardiac oxidative stress biomarkers (4-Hydroxynonenal, HNE; nitrotyrosine, NT), antioxidant enzymes, and NLRP3 inflammasome panel expression are also determined. Our results show a higher ejection and a shortening fraction of the left ventricle function by the end of the fourth cycle. Furthermore, cardiac tissue presented a decreased expression of antioxidant proteins. However, a decrease in IL-1β, TNF-αn, and oxidative stress markers is observed in IHH compared to normobaric hypoxic controls. Non-significant differences were found in protein levels of NLRP3 and caspase-1. IHH exposure determines structural and functional heart changes. These findings suggest that initial states of IHH are beneficial for cardiovascular function and protection.

Reparative effects of chronic intermittent hypobaric hypoxia pre‑treatment on intervertebral disc degeneration in rats.

Previous studies have indicated that chronic intermittent hypobaric hypoxia (CIHH) preconditioning can inhibit TNF-α and other related inflammatory cytokines and exerts protective effect on intervertebral disc degeneration disease (IDD) in rats; however, the mechanism is still unclear. The present study aimed to explore the repair mechanisms of CIHH on IDD in rats. In the experiment, 48 adult Sprague-Dawley rats were selected and randomly divided into an experimental group (CIHH-IDD), a degenerative group (IDD) and a control group (CON). The CIHH-IDD group of rats (n=16) were treated with CIHH (simulated 3000 m altitude, 5 h per day, 28 days; PO2=108.8 mmHg) before disc degeneration surgery. The IDD group of rats (n=16) underwent tail-vertebral intervertebral disc surgery to establish a model of intervertebral disc degeneration. The CON group of rats (n=16) did not receive any treatments. After surgery, the disc height index was calculated using X-ray analysis of rat tail vertebrae, the degeneration process was observed and repair was evaluated by chemically staining degenerative intervertebral disc tissue slices. The expression levels of basic fibroblast growth factor (bFGF), TGFβ1, Collagen I and Collagen II were measured in the intervertebral disc tissue using western blotting; while the expression levels of bFGF, TGFβ1 and hypoxia-inducible factor 1-α (HIF-1α) were measured in rat serum using ELISA. The results demonstrated that: i) The degree of intervertebral disc height degeneration in CIHH-IDD rats was significantly lower compared with that in IDD rats (P<0.05); ii) the expression levels of bFGF, TGFβ1 and HIF-1α were higher in CIHH-IDD rat serum compared with those in IDD rat serum (P<0.05); iii) optical microscopy revealed that the degree of disc degeneration was relatively mild in CIHH-IDD rats; and iv) the protein expression levels of bFGF, TGFβ1 and collagen II were increased in CIHH-IDD rat intervertebral disc tissues compared with those of IDD rats, while the overexpression of collagen I protein was inhibited. Overall, after CIHH pre-treatment, the expression levels of bFGF and TGFβ1 were up-regulated, which play notable roles in repairing degenerative intervertebral discs in rats.

Biomechanical and structural responses of the aorta to intermittent hypobaric hypoxia in a rat model

High altitude hypoxia is a condition experienced by diverse populations worldwide. In addition, several jobs require working shifts where workers are exposed to repetitive cycles of hypobaric hypoxia and normobaric normoxia. Currently, few is known about the biomechanical cardiovascular responses of this condition. In the present study, we investigate the cycle-dependent biomechanical effects of intermittent hypobaric hypoxia (IHH) on the thoracic aorta artery, in terms of both structure and function. To determine the vascular effects of IHH, functional, mechanical and histological approaches were carried out in the thoracic aorta artery, using uniaxial, pre-stretch, ring opening, myography, and histological tests. Three groups of rats were established: control (normobaric normoxia, NN), 4-cycles of intermittent hypoxia (short-term intermittent hypobaric hypoxia, STH), and 10-cycles of intermittent hypoxia (long-term intermittent hypobaric hypoxia, LTH). The pre-stretch and ring opening tests, aimed at quantifying residual strains of the tissues in longitudinal and circumferential directions, showed that the hypoxia condition leads to an increase in the longitudinal stretch and a marked decrease of the circumferential residual strain. The uniaxial mechanical tests were used to determine the elastic properties of the tissues, showing that a general stiffening process occurs during the early stages of the IH (STH group), specially leading to a significative increase in the high strain elastic modulus (E_{2}) and an increasing trend of low strain elastic modulus (E_{1}). In contrast, the LTH group showed a more control-like mechanical behavior. Myography test, used to assess the vasoactive function, revealed that IH induces a high sensitivity to vasoconstrictor agents as a function of hypoxic cycles. In addition, the aorta showed an increased muscle-dependent vasorelaxation on the LTH group. Histological tests, used to quantify the elastic fiber, nuclei, and geometrical properties, showed that the STH group presents a state of vascular fibrosis, with a significant increase in elastin content, and a tendency towards an increase in collagen fibers. In addition, advanced stages of IH (LTH), showed a vascular remodeling effect with a significant increase of internal and external diameters. Considering all the multidimensional vascular effects, we propose the existence of a long-term passive adaptation mechanism and vascular dysfunction as cycle-dependent effects of intermittent exposures to hypobaric hypoxia.

Dysregulation of the Nitric Oxide/Dimethylarginine Pathway in Hypoxic Pulmonary Vasoconstriction—Molecular Mechanisms and Clinical Significance

The pulmonary circulation responds to hypoxia with vasoconstriction, a mechanism that helps to adapt to short-lived hypoxic episodes. When sustained, hypoxic pulmonary vasoconstriction (HPV) may become deleterious, causing right ventricular hypertrophy and failure, and contributing to morbidity and mortality in the late stages of several chronic pulmonary diseases. Nitric oxide (NO) is an important endothelial vasodilator. Its release is regulated, amongst other mechanisms, by the presence of endogenous inhibitors like asymmetric dimethylarginine (ADMA). Evidence has accumulated in recent years that elevated ADMA may be implicated in the pathogenesis of HPV and in its clinical sequelae, like pulmonary arterial hypertension (PAH). PAH is one phenotypic trait in experimental models with disrupted ADMA metabolism. In high altitude, elevation of ADMA occurs during long-term exposure to chronic or chronic intermittent hypobaric hypoxia; ADMA is significantly associated with high altitude pulmonary hypertension. High ADMA concentration was also reported in patients with chronic obstructive lung disease, obstructive sleep apnoea syndrome, and overlap syndrome, suggesting a pathophysiological role for ADMA-mediated impairment of endothelium-dependent, NO-mediated pulmonary vasodilation in these clinically relevant conditions. Improved understanding of the molecular (dys-)regulation of pathways controlling ADMA concentration may help to dissect the pathophysiology and find novel therapeutic options for these diseases.

The effects of copper, zinc and bicarbonate in blood, kidney and liver in rats under intermittent hypobaric hypoxia

Intermittent hypobaric hypoxia is defined as to be below the normal values of partial oxygen pressure at tissue due to hypoxia periods. It can lead to increased reactive oxygen species which causes oxidative damage to DNA, lipids and proteins. The effect of antioxidant defense mechanism varies from tissue to tissue under hypoxic conditions. The aim of our study was to investigate the effects of bicarbonate, copper and zinc on antioxidant statue in blood, liver and kidney tissues under hypoxia.Forty adult male Sprague Dawley rats randomly divided into five groups (Control, Hypoxia, H+Zn, H+Cu and H+HCO3). Rats were exposed hypoxia a daily 8 h for 5 days/week until completing 3 weeks in hypoxia cabin at a simulated pressure of 400–500 mmHg. The animals of H+Zn, H+Cu and H+HCO3 experimental groups received through drinking water 30 mg/kg Zn, 7 mg/kg Cu and 3 mmol/kg NaHCO3, respectively. At the samples of blood, liver and kidney taken from rats at the end of experiment were measured the concentrations of Zn and Cu by ICP-OES device. The values of malondialdehyde (MDA) and glutathione (GSH) and the bicarbonate concentration were also obtained spectrophotometer and ABL800 devices, respectively.According to statistical evaluated, the kidney GSH values showed a significant increase in all experimental groups (p < 0.01). Increase in the plasma GSH values is also due to kidney cells. As a result of our investigation it is seen that the antioxidant response of kidney cells to hypoxia are more effective than applied dose levels of zinc, copper and bicarbonate ions at the study.

The Effect of Chronic Intermittent Hypobaric Hypoxia on Sleep Quality and Melatonin Serum Levels in Chilean Miners.

High-altitude mining is an important economic resource for Chile. These workers are exposed to chronic intermittent hypobaric hypoxia (CIHH), which reduces their sleep quality and increases the risk of accidents and long-term illnesses. Melatonin, a hormone produced by the pineal gland, is a sleep inducer that regulates the circadian cycle and may be altered in populations subjected to CIHH. This work aimed to assess the relationship between altitude, sleep quality, and plasma melatonin concentrations in miners with CIHH exposure. 288 volunteers were recruited from five altitudes (0, 1,600, 2,500, 3,500, and 4,500 m). All volunteers worked for 7 days at altitude, followed by 7 days of rest at sea level. We performed anthropometric assessments, nocturnal oximetry, sleep quality and sleepiness surveys, and serum melatonin levels upon awakening. Although oxygen saturation progressively decreased and heart rate increased at higher altitudes, subjective perception of sleep quality was not significantly different, and sleepiness increased in all groups compared to population at sea level. Similarly, melatonin levels increased at all assessed altitudes compared to the population at sea level. These data confirm that sleep disturbances associated with CIHH increase morning melatonin levels. Therefore, this hormone and could potentially serve as a biomarker of sleep quality.

Adenosine mono-phosphate-activated protein kinase-mammalian target of rapamycin signaling participates in the protective effect of chronic intermittent hypobaric hypoxia on vascular endothelium of metabolic syndrome rats.

Our previous study demonstrated that chronic intermittent hypobaric hypoxia (CIHH) protects vascular endothelium function through ameliorating autophagy in mesenteric arteries of metabolic syndrome (MS) rats. This study aimed to investigate the role of adenosine mono-phosphate-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) signaling in CIHH effect. Six-week-old male Sprague-Dawley rats were divided into control (CON), MS model, CIHH treatment (CIHH), and MS + CIHH groups. Serum pro-inflammatory cytokines were measured. The endothelium dependent relaxation (EDR), endothelial ultrastructure and autophagosomes were observed in mesenteric arteries. The expression of phosphor (p)-AMPKα, p-mTOR, autophagy-related and endoplasmic reticulum stress-related proteins, p-endothelial nitric oxide synthase, and cathepsin D were assayed. In MS rats, pro-inflammatory cytokines were increased, EDR was attenuated, and endothelial integrity was impaired. In addition, the expression level of p-AMPKα and cathepsin D was down-regulated, but the level of p-mTOR was up-regulated. While in MS + CIHH rats, all aforementioned abnormalities were ameliorated, and the beneficial effect of CIHH was cancelled by AMPKα inhibitor. In conclusion, AMPK-mTOR signaling pathway participates in the protection of CIHH on vascular endothelium of MS rats.

12/15–Lipoxygenase debilitates mitochondrial health in intermittent hypobaric hypoxia induced neuronal damage: An in vivo study

High altitude cerebral edema does not fall in routine definition of hypoxia and requires alternative therapeutic strategies. 12/15-Lipoxygenase (12/15 LOX), a key proinflammatory lipid peroxidative enzyme which site specifically inserts into cellular and subcellular membranes and plays an instrumental role in hypobaric hypoxia induced neuropathogenesis. Mitochondria, the master regulator organelles for oxygen consumption and ATP generation are sensitive to intracellular oxygen perturbations and are associated with activation of apoptosis based cell death cascades that seal the fate of the cell. The mechanistic involvement of 12/15 LOX in mitochondria mediated cell death in brain microenvironment during hypobaric hypoxia conditions can be an interesting preposition. In the present study, we have investigated underlying involvement of 12/15 LOX in hypobaric hypoxia (HH) induced disturbance in mitochondrial integrity and its relation with neuronal apoptosis. Male Balb/c mice subjected to simulated HH condition for three consecutive days showed robust increase in intra-hippocampal 12(S)HETE (12/15 LOX metabolite), which was significantly reduced following baicalein (12/15 LOX Inhibitor) treatment. The elevated level of 12(S)HETE following hypobaric hypoxia condition correlated with simultaneous increase in expression of 12/15 LOX in neurons and microglia lining the hippocampal CA3 region. Further, 12/15 LOX gets embedded onto the periphery of mitochondria following HH and a strong correlation has been observed with loss of mitochondrial integrity as evident from increased cytochrome-c in the cytosolic compartment and a subsequent upregulated activity of Caspase-3 and Caspase-9 as well as Bax/Bcl-2 expression ratio. The observed effects seen under HH were reversed upon treatment with baicalein suggesting a critical role of 12/15 LOX in HH induced mitochondrial damage Further, the hypobaric hypoxia-mediated increase in hippocampal pAKT and pmTOR protein expression were significantly ameliorated following 12/15 LOX inhibition, suggesting a mitochondrial involvement. We hereby demonstrate the contribution of 12/15 LOX in disorienting mitochondrial integrity with subsequent release of cytochrome-c in cytosol which drives the neuronal cells to intrinsic mode of cell death during hypobaric hypoxia. The protective role of baicalein by inhibition of 12/15 LOX dependent neuronal cell death and preservation of mitochondrial integrity suggests it to be a plausible therapeutic target in CNS related disorders.

Preconditioning With Intermittent Hypobaric Hypoxia Attenuates Stroke Damage and Modulates Endocytosis in Residual Neurons.

Background: Moderate hypobaric hypoxia induces cerebral ischemic tolerance. We investigated the optimal method for applying hypobaric hypoxia preconditioning at 5,000 m to ischemic brain tissue and combined it with proteomics to determine the mechanisms underlying this effect.Methods: Male SD rats were randomly grouped as S (sham, n = 20), M (middle cerebral artery occlusion [MCAO], n = 28), H2M (intermittent hypobaric hypoxia preconditioned MCAO group, 2 h/day, 10 days, n = 20), H6M (intermittent hypobaric hypoxia preconditioned MCAO group, 6 h/day, 10 days, n = 28), and HpM (persistent hypobaric hypoxia preconditioned MCAO group, 10 days, n = 28). The permanent MCAO model was established based on the Zea Longa method. Infarction was assessed with the modified neurological severity score (mNSS) and 2,3,5-triphenyl tetrazolium chloride staining. The total protein expression of the neuron-specific nuclear protein (NeuN), cysteinyl aspartate specific proteinase 3 (caspase-3), cleaved-caspase-3, and interleukin 6 (IL-6) was determined using western blotting. We assessed the peri-infarct cortex's ultrastructural changes. A label-free proteomic study and western blot verification were performed on the most effective preconditioned group.Results: The H6M group showed a lower infarct volume (p = 0.0005), lower mNSS score (p = 0.0009) than the M group. The H2M showed a lower level of IL-6 (p = 0.0213) than the M group. The caspase-3 level decreased in the H2M (p = 0.0002), H6M (p = 0.0025), and HpM groups (p = 0.0054) compared with that in the M group. Cleaved-caspase-3 expression decreased in the H2M (p = 0.0011), H6M (p < 0.0001), and HpM groups (p < 0.0001) compared with that in the M group. The neurons' ultrastructure and the blood-brain barrier in the peri-infarct tissue improved in the H2M and H6M groups. Immunofluorescence revealed increased NeuN-positive cells in the peri-infarct tissue in the H6M group (p = 0.0003, H6M vs. M). Protein expression of Chmp1a, Arpc5, and Hspa2 factors related to endocytosis were upregulated in the H6M compared with those of the M group (p < 0.05 for all) on western blot verification of label-free proteomics.Conclusions: Intermittent hypobaric hypoxia preconditioning exerts a neuroprotective effect in a rat stroke model. Persistent hypobaric hypoxia stimulation exhibited no significant neuroprotective effect. Intermittent hypoxic preconditioning for 6 h/day for 10 days upregulates key proteins in clathrin-dependent endocytosis of neurons in the cortex.

Intermittent hypobaric hypoxia and cold treatment after gastrocnemius muscle injury enhance redox balance and avoids UPS activation

Intermittent hypobaric hypoxia and cold treatment after gastrocnemius muscle injury enhance redox balance and avoids UPS activation

The Impact of Intermittent Hypobaric Hypoxia Exposures on Triacylglycerol Synthesis in Rat Liver.

In a hypoxic state, fatty acid breakdown reaction may be inhibited due to a lack of oxygen. It is likely that the fatty acids will be stored as triacylglycerol. The aim of this study was to analyse triacylglycerol synthesis in the liver after intermittent hypobaric hypoxia (HH) exposures. Samples are liver tissues from 25 male Wistar rats were divided into 5 groups: control group (normoxia), group I (once HH exposure), group II (twice HH exposures), group III (three-times HH exposures) and group IV (four-times HH exposures). The triacylglycerol level, mRNA expression of HIF-1α and PPAR-γ were measured in rat liver from each group. We demonstrated that triacylglycerol level, mRNA expression of HIF-1α and PPAR-γ is elevated in group I significantly compared to control group. In the intermittent HH groups (group II, III and IV), mRNA expression of HIF-1α and PPAR-γ tends to downregulate near to control group. However, the triacylglycerol level is still found increased in the intermittent HH exposures groups. Significant increasing of triacylglycerol level was found especially in group IV compared to control group. We conclude that intermittent HH exposures will increase the triacylglycerol level in rat liver, supported by the increasing of HIF-1α and PPAR-γ mRNA expression that act as transcription factor to promote triacylglycerol synthesis.

High altitude exposure affects male reproductive parameters: could it also affect the prostate?†.

Living at high altitudes and living with prostatic illness are two different conditions closely related to a hypoxic environment. People at high altitudes exposed to acute, chronic or intermittent hypobaric hypoxia turn on several mechanisms at the system, cellular, and molecular level to cope with oxygen atmosphere scarcity maintaining the oxygen homeostasis. This exposure affects the whole organism and function of many systems, such as cardiovascular, respiratory, and reproductive. On the other hand, malignant prostate is related to the scarcity of oxygen in the tissue microenvironment due to its low availability and high consumption due to the swift cell proliferation rates. Based on the literature, this similarity in the oxygen scarcity suggests that hypobaric hypoxia, and other common factors between these two conditions, could be involved in the aggravation of the pathological prostatic status. However, there is still a lack of evidence in the association of this disease in males at high altitudes. This review aims to examine the possible mechanisms that hypobaric hypoxia might negatively add to the pathological prostate function in males who live and work at high altitudes. More profound investigations of hypobaric hypoxia's direct action on the prostate could help understand this exposure's effect and prevent worse prostate illness impact in males at high altitudes.

Effect of Chronic Intermittent Hypobaric Hypoxia on Cardiac Function in Female Metabolic Syndrome Rats

Effect of Chronic Intermittent Hypobaric Hypoxia on Cardiac Function in Female Metabolic Syndrome Rats

Oxidative stress in the heart of rats exposed to acute intermittent hypobaric hypoxia

Oxidative stress in the heart of rats exposed to acute intermittent hypobaric hypoxia

Chronic intermittent hypobaric hypoxia attenuates ischemic limb injury by promoting angiogenesis in mice.

This study aimed to evaluate the protective effect of chronic intermittent hypobaric hypoxia (CIHH) against limb ischemic injury. C57BL/6 mice were randomly divided into three groups: limb ischemic injury group (Ischemia, induced by ligation and excision of the left femoral artery), limb ischemia following CIHH pretreatment group (CIHH+Ischemia, simulated a 5000 m altitude hypoxia, 6h per day for 28days, before induction of hind-limb ischemia), and sham group (Sham). The blood flow in the mouse models of hind-limb ischemia was examined using laser doppler imaging. The functional and morphological performance of ischemic muscle was evaluated using contraction force and hematoxylin-eosin and Masson's trichrome staining. Angiogenesis was determined by immunohistochemistry staining of the endothelial markers CD31 and CD34. The protein expressions of angiogenesis-related genes were detected using Western blot assay. Chronic ischemia resulted in reduced blood perfusion, decreased contraction tension, and morphological destruction in gastrocnemius muscle. CIHH pretreatment increased the contractile force and muscle fiber diameter and decreased necrosis and fibrosis of the ischemic muscle. Also, CIHH significantly increased the density of CD31+ and CD34+ cells and promoted the expression of angiogenesis-related molecules in ischemic muscle. These data demonstrate that CIHH has a protective effect against chronic limb ischemia by promoting angiogenesis.

Adaptation to intermittent hypoxia prevents the decrease in cerebral vascular density in rats with experimental Alzheimer’s disease

Introduction. Patients with Alzheimer’s disease (AD) have reduced cerebral vascular density (VD), which impairs blood flow to neurons and may contribute to progression of AD. Earlier we showed that prior adaptation to intermittent hypobaric hypoxia (IHH) prevented memory loss and degeneration of cortical neurons in rats with experimental AD (EAD). The aim of this study was to test if IHH might prevent EAD-induced vascular rarefaction in rats. Materials and methods. EAD was induced with bilateral injection of neurotoxic beta-amyloid peptide fragment (A) (25–35) into n. basalis magnocellularis. IHH was simulated at a 4,000 m altitude, for 4 hours a day, for 14 days. Brain blood vessels were stained by transcardiac infusion of Indian ink; brain sections were stained with 0.3 % cresyl violet by Nissle method. Vascular density was assessed in the cortex and hippocampus using the Infinity Analysis Software. Results. In the EAD rats, VD was significantly decreased in the hippocampus (13.3±0.9 vs 17.8±1.0 in field of view, FOV, p&lt;0.03) and in the cortex (17.3±1.5 vs 22.3±1.3 in FOV, p&lt;0.03). AIH increased VD in the hippocampus to 27.0±3.5 in FOV (p=0.01) and in cortex to 26.0±1.1 in FOV (p&lt;0.03). In EAD+AIH rats, VD did not differ significantly from the control rats neither in the hippocampus, nor in the cortex. AIH may stimulate angiogenesis through hypoxia inducible factor-1α-mediated expression of vascular endothelial growth factor and/or by increasing expression and activity of antioxidant enzymes. Conclusion. One of the mechanisms of AIH beneficial effect in AD-related neurodegeneration is preserving the capability for compensatory angiogenesis in brain.