Search Results (27)

Hypoxia can adversely affect multiple organ systems. This study investigated the impact of intermittent hypoxia on serotonin levels and depression-like behaviors across distinct neuroanatomical regions. Sixteen adult female Wistar albino rats were divided into two groups: control (n = 8) and hypoxia (n = 8). The hypoxia group was exposed to a simulated altitude of 3000 for 5 h daily over 14 days. Behavioral assessments included locomotor activity (open field test) and depression-like behaviors (forced swimming test). Serotonin levels were quantified via ELISA in the prefrontal cortex, striatum, thalamus, hypothalamus, hippocampus, and serum. Intermittent hypoxia did not alter locomotor activity (p > 0.05) but significantly increased depression-like behavior (p < 0.05), accompanied by a pronounced reduction in swimming behavior (p < 0.0001), a marker associated with serotonergic function. Serotonin levels were significantly reduced in the prefrontal cortex (p < 0.005) and striatum (p < 0.05), while no changes were observed in other regions or serum (p > 0.05). These findings demonstrate that intermittent hypoxia induces depression-like behaviors and region-specific serotonin depletion, particularly in the prefrontal cortex and striatum. This underscores the need to evaluate hypoxia-related brain health implications in conditions such as sleep apnea and acute mountain sickness. Full article

Hyperbaric oxygenation (HBO₂) can modify gene and protein expression, signaling pathways, and vascular function, leading to altered vasomotor responses. Adenosine receptors (ARs) may mediate these effects by modulating vasoactivity. This study investigated flow-induced dilation (FID) and hypoxia-induced dilation (HID) in the presence or absence of A1R/A2aR agonists (CCPA and CGS-21680, respectively) and antagonists (DPCPX and SCH-58261, respectively) in isolated middle cerebral arteries (MCAs) from Sprague Dawley rats of both sexes and the direct dose-dependent effects of A1R and A2aR agonists on the vascular reactivity of MCAs. Rats were exposed to either acute HBO₂ (Ac-HBO₂) or intermittent HBO₂ over four days (In-HBO₂). Ac-HBO₂ impaired vascular responses to A1R and A2aR agonists and significantly decreased FID and HID. In both Ac-HBO₂ and In-HBO₂, A1R modulation did not significantly affect FID or HID. A2aR stimulation reduced FID in the In-HBO₂ group, while A2aR antagonism had no significant effect on HID. However, the A2aR agonist’s presence enhanced HID in In-HBO₂-exposed rats. Protein expression of A1R and A2aR decreased after Ac-HBO₂, while gene expression increased following In-HBO₂. These findings suggest that ARs play a role in HBO₂-induced vasoreactivity, which possibly changes in MCA, potentially via the modulation of ARs gene and protein expression. Full article

The carotid body (CB) senses arterial PO₂, PCO₂, and pH levels, eliciting reflex responses to maintain cardiorespiratory homeostasis. Chronic intermittent hypoxia (CIH), the hallmark of obstructive sleep apnea, elicits autonomic and cardiorespiratory alterations that are attributed to an enhanced CB chemosensory responsiveness to hypoxia, which in turn activates neurons and glial cells in the nucleus of the tractus solitarius (NTS). Although the CB contribution to the CIH-induced pathological alterations is well-known, the underlying mechanisms are not fully understood. A growing body of new evidence suggests a crucial role for ROS in acute CB oxygen sensing, as well as in the potentiation of chemosensory discharge and the activation of the central chemoreflex pathway in CIH. Indeed, it has been proposed that acute hypoxia disrupts mitochondrial electron transport, increasing ROS and NADH in the chemoreceptor cells, which inhibit voltage-gated K⁺ channels, producing cell depolarization, Ca²⁺ entry, and release of excitatory transmitters. In addition, new evidence supports that the enhanced CB afferent discharge contributes to persistent CIH-induced cardiorespiratory alterations, likely triggering neuroinflammation in the NTS. Thus, in this review, we will examine the experimental evidence that supports the involvement of ROS in the acute O₂ sensing process, and their role in the enhanced CB chemosensory discharges, the glial-related inflammation in the NTS, and the cardiorespiratory alterations induced by CIH. Full article

The aim of this study was to evaluate the combined effects of L-arginine, intermittent hypoxia training (IHT), and acute stress on oxygen-dependent processes in rats, including mitochondrial oxidative phosphorylation, microsomal oxidation, and the intensity of lipoperoxidation processes. In addition, our study investigated how the modulatory effect of the NO synthase mechanism on the concentration of catecholamines (CA), such as adrenaline and noradrenaline, and their biosynthetic precursors (DOPA, dopamine) varies depending on the cholinergic (acetylcholine, Ach-acetylcholinesterase, AChE) status in rats. This study investigated the protective stress-limiting effects of L-arginine impact and IHT in the blood and liver of rats. The results showed that L-arginine promoted the maintenance of NAD-dependent oxidation in mitochondria, which was detrimental compared to succinate oxidation, and was accompanied by depletion of respiratory activity reserves under stress induced by high concentrations of CA. The interdependence of SC-dependent oxidation and the functional role of NAD-dependent substrate oxidation in the mitochondrial respiratory chain in stress conditions induced using inhibitors revealed the importance of the NO system. Administration of L-arginine during the IHT course prior to stress exposure increased the compensatory capacity of the organism. L-arginine increased the compensatory capacity of the sympathoadrenal system in stress-exposed rats. In the early stages of IHT, modulation of the CA concentration was observed with a concomitant increase in lipoperoxidation processes, and in the final stages of IHT, the CA concentrations increased, but there was also an inhibition of lipoperoxidation, which was particularly enhanced by the administration of L-arginine. The increase in blood concentrations of CA and ACh was accompanied by a decrease in AChE activity at different stages of adaptation to hypoxia induced by IHT (days 5, 10, and 14). Thus, the IHT method significantly mobilises the reserve capacity of oxygen-dependent processes through the system of CA, ACh-AChE mediated by nitric oxide. Full article

Background/Objectives: Mental disorders pose a significant public health challenge, affecting millions worldwide. Given the limitations of current therapies, many patients experience inadequate responses and adverse effects. Intermittent hypoxia (IH) has demonstrated anxiolytic, antidepressant, and neuroprotective properties in various protocols. This study investigated the effects of acute IH (13% O₂, 1 h), fluoxetine (FLX) and their combination on depression-like behavior, serum corticosterone, and inflammatory cytokine levels induced by acute restraint stress in C57BL/6 female mice. Methods: Behavioral assessments included the tail suspension test, forced swim test, and open field test. Results: The combined IH + FLX treatment exhibited a synergistic effect, reducing immobility time and increasing latency time, respectively, in the tail suspension test (46%, p = 0.0014; 73%, p = 0.0033) and forced swim test (56%, p = 0.0082; 48%, p = 0.0322) compared to the ARS group. Biochemical analysis revealed that individual and combined treatments significantly reduced most inflammatory interleukins by up to 96%. Corticosterone levels were reduced by 30% only in the IH group. Conclusions: These findings highlight the potential of a one-hour IH session, particularly when combined with fluoxetine, to alleviate depressive-like behaviors and exert anti-inflammatory effects, suggesting a promising therapeutic approach for depression. Full article

Comprehending the immune defense mechanisms of new aquaculture species, such as the Chilean meagre (Cilus gilberti), is essential for sustaining large-scale production. Two bioassays were conducted to assess the impact of acute and intermittent hypoxia on the antibacterial activity of juvenile Chilean meagre epidermal mucus against the potential pathogens Vibrio anguillarum and Vibrio ordalii. Lysozyme and peroxidase activities were also measured. In general, fish exposed to hypoxia showed a 9–30% reduction in mucus antibacterial activity at the end of hypoxic periods and after stimulation with lipopolysaccharide. However, following water reoxygenation, the activity of non-stimulated fish was comparable to that of fish in normoxic conditions, inhibiting bacterial growth by 35–52%. In the case of fish exposed to chronic hypoxia, the response against V. anguillarum increased by an additional 19.8% after 6 days of control inoculation. Lysozyme exhibited a similar pattern, while no modulation of peroxidase activity was detected post-hypoxia. These results highlight the resilience of C. gilberti to dissolved oxygen fluctuations and contribute to understanding the potential of mucus in maintaining the health of cultured fish and the development of future control strategies. Full article

Both obstructive sleep apnea (OSA) and acute lower respiratory tract infections (LRTIs) are important global health issues. The pathophysiological links between OSA and LRTIs include altered immune responses due to chronic intermittent hypoxia and sleep fragmentation, increased aspiration risk, and a high burden of comorbidities. In this narrative review, we evaluated the current evidence on the association between OSA and the incidence and outcomes of acute LRTIs in adults, specifically community-acquired pneumonia and viral pneumonia caused by influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Studies have demonstrated that OSA patients are more likely to develop bacterial pneumonia and exhibit a higher risk of invasive pneumococcal disease. The risk intensifies with the severity of OSA, influencing hospitalization rates and the need for intensive care. OSA is also associated with an increased risk of contracting influenza and suffering more severe disease, potentially necessitating hospitalization. Similarly, OSA contributes to increased COVID-19 disease severity, reflected by higher rates of hospitalization, longer hospital stays, and a higher incidence of acute respiratory failure. The effect of OSA on mortality rates from these infections is, however, somewhat ambiguous. Finally, we explored antibiotic therapy for OSA patients with LRTIs, addressing care settings, empirical regimens, risks, and pharmacokinetic considerations. Given the substantial burden of OSA and its significant interplay with acute LRTIs, enhanced screening, targeted vaccinations, and optimized management strategies for OSA patients should be prioritized. Full article

This study explores the effects of normobaric hypoxia and intermittent hypoxic training (IHT) on the physiological condition of the cardiac muscle in swimmers. Hypoxia has been reported to elicit both beneficial and adverse changes in the cardiovascular system, but its impact on the myocardium during acute exercise and altitude/hypoxic training remains less understood. We aimed to determine how a single bout of intense interval exercise and a four-week period of high-intensity endurance training under normobaric hypoxia affect cardiac marker activity in swimmers. Sixteen young male swimmers were divided into two groups: one undergoing training in hypoxia and the other in normoxia. Cardiac markers, including troponin I and T (cTnI and cTnT), heart-type fatty acid-binding protein (H-FABP), creatine kinase-MB isoenzyme (CK-MB), and myoglobin (Mb), were analyzed to assess the myocardium’s response. We found no significant differences in the physiological response of the cardiac muscle to intense physical exertion between hypoxia and normoxia. Four weeks of IHT did not alter the resting levels of cTnT, cTnI, and H-FABP, but it resulted in a noteworthy decrease in the resting concentration of CK-MB, suggesting enhanced cardiac muscle adaptation to exercise. In contrast, a reduction in resting Mb levels was observed in the control group training in normoxia. These findings suggest that IHT at moderate altitudes does not adversely affect cardiac muscle condition and may support cardiac muscle adaptation, affirming the safety and efficacy of IHT as a training method for athletes. Full article

Coordinated activation of sympathetic and respiratory nervous systems is crucial in responses to noxious stimuli such as intermittent hypoxia. Acute intermittent hypoxia (AIH) is a valuable model for studying obstructive sleep apnea (OSA) pathophysiology, and stimulation of breathing during AIH is known to elicit long-term changes in respiratory and sympathetic functions. The aim of this study was to record the renal sympathetic nerve activity (RSNA) and phrenic nerve activity (PNA) during the AIH protocol in rats exposed to monoanesthesia with sevoflurane or isoflurane. Adult male Sprague-Dawley rats (n = 24; weight: 280–360 g) were selected and randomly divided into three groups: two experimental groups (sevoflurane group, n = 6; isoflurane group, n = 6) and a control group (urethane group, n = 12). The AIH protocol was identical in all studied groups and consisted in delivering five 3 min-long hypoxic episodes (fraction of inspired oxygen, FiO₂ = 0.09), separated by 3 min recovery intervals at FiO₂ = 0.5. Volatile anesthetics, isoflurane and sevoflurane, blunted the RSNA response to AIH in comparison to urethane anesthesia. Additionally, the PNA response to acute intermittent hypoxia was preserved, indicating that the respiratory system might be more robust than the sympathetic system response during exposure to acute intermittent hypoxia. Full article

The renin–angiotensin system (RAS) and hypoxia have a complex interaction: RAS is activated under hypoxia and activated RAS aggravates hypoxia in reverse. Renin is an aspartyl protease that catalyzes the first step of RAS and tightly regulates RAS activation. Here, we outline kidney renin expression and release under hypoxia and discuss the putative mechanisms involved. It is important that renin generally increases in response to acute hypoxemic hypoxia and intermittent hypoxemic hypoxia, but not under chronic hypoxemic hypoxia. The increase in renin activity can also be observed in anemic hypoxia and carbon monoxide-induced histotoxic hypoxia. The increased renin is contributed to by juxtaglomerular cells and the recruitment of renin lineage cells. Potential mechanisms regulating hypoxic renin expression involve hypoxia-inducible factor signaling, natriuretic peptides, nitric oxide, and Notch signaling-induced renin transcription. Full article

Obstructive sleep apnoea (OSA) is a strong independent risk factor for atrial fibrillation (AF). Emerging clinical data cite adverse effects of OSA on AF induction, maintenance, disease severity, and responsiveness to treatment. Prevention using continuous positive airway pressure (CPAP) is effective in some groups but is limited by its poor compliance. Thus, an improved understanding of the underlying arrhythmogenic mechanisms will facilitate the development of novel therapies and/or better selection of those currently available to complement CPAP in alleviating the burden of AF in OSA. Arrhythmogenesis in OSA is a multifactorial process characterised by a combination of acute atrial stimulation on a background of chronic electrical, structural, and autonomic remodelling. Chronic intermittent hypoxia (CIH), a key feature of OSA, is associated with long-term adaptive changes in myocyte ion channel currents, sensitising the atria to episodic bursts of autonomic reflex activity. CIH is also a potent driver of inflammatory and hypoxic stress, leading to fibrosis, connexin downregulation, and conduction slowing. Atrial stretch is brought about by negative thoracic pressure (NTP) swings during apnoea, promoting further chronic structural remodelling, as well as acutely dysregulating calcium handling and electrical function. Here, we provide an up-to-date review of these topical mechanistic insights and their roles in arrhythmia. Full article

Patients presenting with insufficient tissue oxygenation and impaired lung function as in acute respiratory distress syndrome (ARDS) frequently require mechanical ventilation with supplemental oxygen. Despite the lung being used to experiencing the highest partial pressure of oxygen during healthy breathing, the organ is susceptible to oxygen-induced injury at supraphysiological concentrations. Hyperoxia-induced lung injury (HALI) has been regarded as a second hit to pre-existing lung injury and ventilator-induced lung injury (VILI) attributed to oxidative stress. The injured lung has a tendency to form atelectasis, a cyclic collapse and reopening of alveoli. The affected lung areas experience oxygen conditions that oscillate between hyperoxia and hypoxia rather than remaining in a constant hyperoxic state. Mechanisms of HALI have been investigated in many animal models previously. These studies provided insights into the effects of hyperoxia on the whole organism. However, cell type-specific responses have not been dissected in detail, but are necessary for a complete mechanistic understanding of ongoing pathological processes. In our study, we investigated the effects of constant and intermittent hyperoxia on the lung endothelium from a mouse by an in vitro proteomic approach. We demonstrate that these oxygen conditions have characteristic effects on the pulmonary endothelial proteome that underlie the physiological (patho)mechanisms. Full article

The Lusitanian toadfish, Halobatrachus didactylus is a marine teleost found in coastal lagoons and river estuaries, often exposed to important changes in salinity, temperature and reduced oxygen. Sedentary species, with strong site fidelity and low migratory ability along the temperature gradient such as this may be especially impacted by climate change. We aimed at establishing the tolerance limits to acute temperature and oxygen changes, and evaluate respiratory and metabolic responses in chronic control, warm and hypoxic (35% O₂) conditions. Critical temperature maximum (CTmax) was determined in 12 individuals exposed to a temperature ramp of 3 °C per hour starting at 18 °C, and was found to be 34.8 ± 0.66 °C. Critical oxygen level (PO₂crit) was determined in 8 fish at 18 °C while performing intermittent respirometry and oxygen depletion was created by nitrogen injection in the tank. PO₂crit was calculated as the inflexion point between oxyregulation and oxyconformation, which was found to be around 1.2 mgO₂/L, but fish survived down to 3% O₂, recovering from 0.2 mgO₂/L but showing increased hematocrit (Hct), red blood cell (RBC) counts and blood pH. We also quantified routine aerobic scope and daily activity patterns, finding this fish to be extremely sedentary. H. didactylus showed one of the lowest daytime basal metabolic rates (MR) found in the literature but activity increased significantly at night (over two-fold when closed inside the metabolic chambers). The effect of temperature on metabolic rate (MR) was evaluated using a temperature ramp ranging from 8 to 32 °C (1 °C/h). Acute temperature changes resulted in a steady increase in MR up to circa 29 °C, beyond which MR become increasingly variable, especially among smaller individuals. Indeed, small fish appear to show high- and low-MR groups, and were more susceptible to heat and hypoxia than larger individuals. In chronic acclimation, the MR was increased by 3- and 4-fold (hypoxia vs. normoxia) in fish at 28 °C in relation to those at 12 °C. Standard MR were not statistically different between normoxia and hypoxia at 12 °C, but maximum MR in hypoxia was only about 2/3 of that in normoxia. Fish in high temperature lost weight (mean −3.1%) and had higher metabolism, while in low temperature, weight increased (mean +9.3%) and metabolism was low, and HIS was significantly lower in high temperature groups. Fish in hypoxic conditions showed consistently high Hct but not RBC or hemoglobin (Hb). Overall this study indicates that H. didactylus is highly tolerant to hypoxia and temperature variations. It remains to be seen if other populations along the Atlantic coast show similar metrics. The measured CTmax is close to the actual maximum temperature possible to experience in Ria Formosa ponds during summer, and it would not be unexpected to find this species establishing stable populations in other regions if climate change forces it out of its actual distribution. Full article

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. Full article

Several diseases associated with high-altitude exposure affect unacclimated individuals. These diseases include acute mountain sickness (AMS), high-altitude cerebral edema (HACE), high-altitude pulmonary edema (HAPE), chronic mountain sickness (CMS), and, notably, high-altitude pulmonary hypertension (HAPH), which can eventually lead to right ventricle hypertrophy and heart failure. The development of these pathologies involves different molecules and molecular pathways that might be related to oxidative stress. Studies have shown that acute, intermittent, and chronic exposure to hypobaric hypoxia induce oxidative stress, causing alterations to molecular pathways and cellular components (lipids, proteins, and DNA). Therefore, the aim of this review is to discuss the oxidative molecules and pathways involved in the development of high-altitude diseases. In summary, all high-altitude pathologies are related to oxidative stress, as indicated by increases in the malondialdehyde (MDA) biomarker and decreases in superoxide dismutase (SOD) and glutathione peroxidase (GPx) antioxidant activity. In addition, in CMS, the levels of 8-iso-PGF2α and H₂O₂ are increased, and evidence strongly indicates an increase in Nox4 activity in HAPH. Therefore, antioxidant treatments seem to be a promising approach to mitigating high-altitude pathologies. Full article