Carotid body chemoreceptors: physiology, pathology, and implications for health and disease.

The carotid body (CB) is the main peripheral chemoreceptor for arterial respiratory gases O2 and CO2 and pH, eliciting reflex ventilatory, cardiovascular, and humoral responses to maintain homeostasis. This review examines the fundamental biology underlying CB chemoreceptor function, its contribution to integrated physiological responses, and its role in maintaining health and potentiating disease. Emphasis is placed on 1) transduction mechanisms in chemoreceptor (type I) cells, highlighting the role played by the hypoxic inhibition of O2-dependent K+ channels and mitochondrial oxidative metabolism, and their modification by intracellular molecules and other ion channels; 2) synaptic mechanisms linking type I cells and petrosal nerve terminals, focusing on the role played by the main proposed transmitters and modulatory gases, and the participation of glial cells in regulation of the chemosensory process; 3) integrated reflex responses to CB activation, emphasizing that the responses differ dramatically depending on the nature of the physiological, pathological, or environmental challenges, and the interactions of the chemoreceptor reflex with other reflexes in optimizing oxygen delivery to the tissues; and 4) the contribution of enhanced CB chemosensory discharge to autonomic and cardiorespiratory pathophysiology in obstructive sleep apnea, congestive heart failure, resistant hypertension, and metabolic diseases and how modulation of enhanced CB reactivity in disease conditions may attenuate pathophysiology.

Carotid body contribution to the physio-pathological consequences of intermittent hypoxia: role of nitro-oxidative stress and inflammation.

Obstructive sleep apnoea (OSA), characterized by chronic intermittent hypoxia (CIH), is considered to be an independent risk for hypertension. The pathological cardiorespiratory consequences of OSA have been attributed to systemic oxidative stress, inflammation and sympathetic overflow induced by CIH, but an emerging body of evidence indicates that a nitro-oxidative and pro-inflammatory milieu within the carotid body (CB) is involved in the potentiation of CB chemosensory responses to hypoxia, which contribute to enhance the sympathetic activity. Accordingly, autonomic and cardiovascular alterations induced by CIH are critically dependent on an abnormally heightened CB chemosensory input to the nucleus of tractus solitarius (NTS), where second-order neurons project onto the rostral ventrolateral medulla (RVLM), activating pre-sympathetic neurons that control pre-ganglionic sympathetic neurons. CIH produces oxidative stress and neuroinflammation in the NTS and RVLM, which may contribute to the long-term irreversibility of the CIH-induced alterations. This brief review is mainly focused on the contribution of nitro-oxidative stress and pro-inflammatory molecules on the hyperactivation of the hypoxic chemoreflex pathway including the CB and the brainstem centres, and whether the persistence of autonomic and cardiorespiratory alterations may depend on the glial-related neuroinflammation induced by the enhanced CB chemosensory afferent input.

Carotid Body Inflammation: Role in Hypoxia and in the Anti-inflammatory Reflex.

Emergent evidence indicates that the carotid body (CB) chemoreceptor may sense systemic inflammatory molecules and is an afferent arm of the anti-inflammatory reflex. Moreover, a proinflammatory milieu within the CB is involved in the enhanced CB chemosensory responsiveness to oxygen following sustained and intermittent hypoxia. In this review, we focus on the physiopathological participation of CBs in inflammatory diseases, such as sepsis and intermittent hypoxia.

Hyperhidrosis in sleep disorders - A narrative review of mechanisms and clinical significance.

Hyperhidrosis is characterized by excessive sweating beyond thermoregulatory needs that affects patients' quality of life. It results from an excessive stimulation of eccrine sweat glands in the skin by the sympathetic nervous system. Hyperhidrosis may be primary or secondary to an underlying cause. Nocturnal hyperhidrosis is associated with different sleep disorders, such as obstructive sleep apnea, insomnia, restless legs syndrome/periodic limb movement during sleep and narcolepsy. The major cause of the hyperhidrosis is sympathetic overactivity and, in the case of narcolepsy type 1, orexin deficiency may also contribute. In this narrative review, we will provide an outline of the possible mechanisms underlying sudomotor dysfunction and the resulting nocturnal hyperhidrosis in these different sleep disorders and explore its clinical relevance.

Chemogenetic inhibition of NTS astrocytes normalizes cardiac autonomic control and ameliorate hypertension during chronic intermittent hypoxia.

BACKGROUND: Obstructive sleep apnea (OSA) is characterized by recurrent episodes of chronic intermittent hypoxia (CIH), which has been linked to the development of sympathoexcitation and hypertension. Furthermore, it has been shown that CIH induced inflammation and neuronal hyperactivation in the nucleus of the solitary tract (NTS), a key brainstem region involved in sympathetic and cardiovascular regulation. Since several studies have proposed that NTS astrocytes may mediate neuroinflammation, we aimed to determine the potential contribution of NTS-astrocytes on the pathogenesis of CIH-induced hypertension. RESULTS: Twenty-one days of CIH induced autonomic imbalance and hypertension in rats. Notably, acute chemogenetic inhibition (CNO) of medullary NTS astrocytes using Designer Receptors Exclusively Activated by Designers Drugs (DREADD) restored normal cardiac variability (LF/HF: 1.1 ± 0.2 vs. 2.4 ± 0.2 vs. 1.4 ± 0.3, Sham vs. CIH vs. CIH + CNO, respectively) and markedly reduced arterial blood pressure in rats exposed to CIH (MABP: 82.7 ± 1.2 vs. 104.8 ± 4.4 vs. 89.6 ± 0.9 mmHg, Sham vs. CIH vs. CIH + CNO, respectively). In addition, the potentiated sympathoexcitation elicit by acute hypoxic chemoreflex activation in rats exposed to CIH was also completely abolished by chemogenetic inhibition of NTS astrocytes using DREADDs. CONCLUSION: Our results support a role for NTS astrocytes in the maintenance of heightened sympathetic drive and hypertension during chronic exposure to intermittent hypoxia mimicking OSA.

The Beneficial Effect of the Blockade of Stim-Activated TRPC-ORAI Channels on Vascular Remodeling and Pulmonary Hypertension Induced by Intermittent Hypoxia Is Independent of Oxidative Stress.

Obstructive sleep apnea (OSA), a sleep breathing disorder featured by chronic intermittent hypoxia (CIH), is associated with pulmonary hypertension (PH). Rats exposed to CIH develop systemic and lung oxidative stress, pulmonary vascular remodeling, and PH and overexpress Stim-activated TRPC-ORAI channels (STOC) in the lung. Previously, we demonstrated that 2-aminoethyl-diphenylborinate (2-APB)-treatment, a STOC-blocker, prevents PH and the overexpression of STOC induced by CIH. However, 2-APB did not prevent systemic and pulmonary oxidative stress. Accordingly, we hypothesize that the contribution of STOC in the development of PH induced by CIH is independent of oxidative stress. We measured the correlation between right ventricular systolic pressure (RVSP) and lung malondialdehyde (MDA) with the gene expression of STOC and morphological parameters in the lung from control, CIH-treated, and 2-APB-treated rats. We found correlations between RVSP and increased medial layer and STOC pulmonary levels. 2-APB-treated rats showed a correlation between RVSP and the medial layer thickness, α-actin-ir, and STOC, whereas RVSP did not correlate with MDA levels in CIH and 2-APB-treated rats. CIH rats showed correlations between lung MDA levels and the gene expression of TRPC1 and TRPC4. These results suggest that STOC channels play a key role in developing CIH-induced PH that is independent from lung oxidative stress.

Chronic hypoxia changes gene expression profile of primary rat carotid body cells: consequences on the expression of NOS isoforms and ET-1 receptors.

Sustained chronic hypoxia (CH) produces morphological and functional changes in the carotid body (CB). Nitric oxide (NO) and endothelin-1 (ET-1) play a major role as modulators of the CB oxygen chemosensory process. To characterize the effects of CH related to normoxia (Nx) on gene expression, particularly on ET-1 and NO pathways, primary cultures of rat CB cells were exposed to 7 days of CH. Total RNA was extracted, and cDNA-32P was synthesized and hybridized with 1,185 genes printed on a nylon membrane Atlas cDNA Expression Array. Out of 324 differentially expressed genes, 184 genes were upregulated, while 140 genes were downregulated. The cluster annotation and protein network analyses showed that both NO and ET-1 signaling pathways were significantly enriched and key elements of each pathway were differentially expressed. Thus, we assessed the effect of CH at the protein level of nitric oxide synthase (NOS) isoforms and ET-1 receptors. CH induced an increase in the expression of endothelial NOS, inducible NOS, and ETB. During CH, the administration of SNAP, a NO donor, upregulated ETB. Treatment with Tezosentan (ET-1 receptor blocker) during CH upregulated all three NOS isoforms, while the NOS blocker L-NAME induced upregulation of iNOS and ETB and downregulated the protein levels of ETA. These results show that CH for 7 days changed the cultured cell CB gene expression profile, the NO and ET-1 signaling pathways were highly enriched, and these two signaling pathways interfered with the protein expression of each other.

Potential Contribution of Carotid Body-Induced Sympathetic and Renin-Angiotensin System Overflow to Pulmonary Hypertension in Intermittent Hypoxia.

PURPOSE OF REVIEW: Obstructive sleep apnea (OSA), featured by chronic intermittent hypoxia (CIH), is an independent risk for systemic hypertension (HTN) and is associated with pulmonary hypertension (PH). The precise mechanisms underlying pulmonary vascular remodeling and PH in OSA are not fully understood. However, it has been suggested that lung tissue hypoxia, oxidative stress, and pro-inflammatory mediators following CIH exposure may contribute to PH. RECENT FINDINGS: New evidences obtained in preclinical OSA models support that an enhanced carotid body (CB) chemosensory reactiveness to oxygen elicits sympathetic and renin-angiotensin system (RAS) overflow, which contributes to HTN. Moreover, the ablation of the CBs abolished the sympathetic hyperactivity and HTN in rodents exposed to CIH. Accordingly, it is plausible that the enhanced CB chemosensory reactivity may contribute to the pulmonary vascular remodeling and PH through the overactivation of the sympathetic-RAS axis. This hypothesis is supported by the facts that (i) CB stimulation increases pulmonary arterial pressure, (ii) denervation of sympathetic fibers in pulmonary arteries reduces pulmonary remodeling and pulmonary arterial hypertension (PAH) in humans, and (iii) administration of angiotensin-converting enzyme (ACE) or blockers of Ang II type 1 receptor (ATR1) ameliorates pulmonary remodeling and PH in animal models. In this review, we will discuss the supporting evidence for a plausible contribution of the CB-induced sympathetic-RAS axis overflow on pulmonary vascular remodeling and PH induced by CIH, the main characteristic of OSA.

Translating carotid body function into clinical medicine.

The carotid body (CB) is considered the main O2 chemoreceptor, which contributes to cardiorespiratory homeostasis and ventilatory acclimatization. In clinical medicine, the most common pathologies associated with the CB are tumours. However, a growing body of evidence supports the novel idea that an enhanced CB chemosensory discharge contributes to the autonomic dysfunction and pathological consequences in obstructive sleep apnoea (OSA), hypertension, systolic heart failure (HF) and cardiometabolic diseases. Heightened CB chemosensory reactivity elicited by oxidative stress has been involved in sympathetic hyperactivity, cardiorespiratory instability, hypertension and insulin resistance. CB ablation, which reduces sympathetic hyperactivity, decreases hypertension in animal models of OSA and hypertension, eliminates breathing instability and improves animal survival in HF, and restores insulin tolerance in cardiometabolic models. Thus, data obtained from preclinical studies highlight the importance of the CB in the progression of sympathetic-related diseases, supporting the idea that appeasing the enhanced CB chemosensory drive may be useful in improving cardiovascular, respiratory and endocrine alterations. Accordingly, CB ablation has been proposed and used as a treatment for moderating resistant hypertension and HF-induced sympathetic hyperactivity in humans. First-in-human studies have shown that CB ablation reduces sympathetic overactivity, transiently reduces severe hypertension and improves quality of life in HF patients. Thus, CB ablation would be a useful therapy to reverse sympathetic overactivation in HF and severe hypertension, but caution is required before it is widely used due to the crucial physiological function played by the CB. Further studies in preclinical models are required to assess side-effects of CB ablation.

Carotid Body Ablation: a New Target to Address Central Autonomic Dysfunction.

PURPOSE OF REVIEW: An abnormal heightened carotid body (CB) chemoreflex, which produces autonomic dysfunction and sympathetic overactivation, is the common hallmark of obstructive sleep apnea (OSA), resistant hypertension, systolic heart failure (HF), and cardiometabolic diseases. Accordingly, it has been proposed that the elimination of the CB chemosensory input to the brainstem may reduce the autonomic and cardiorespiratory alterations in sympathetic-associated diseases in humans. RECENT FINDINGS: A growing body of evidence obtained in preclinical animal models support that an enhanced CB discharge produces sympathetic hyperactivity, baroreflex sensitivity and heart rate variability impairment, breathing instability, hypertension, and insulin resistance. The elimination CB chemosensory input reduces the sympathetic hyperactivity, the elevated arterial blood pressure in OSA and hypertensive models, abolishes breathing instability and improves animal survival in HF models, and restores insulin tolerance in metabolic models. These results highlight the role played by the enhanced CB drive in the progression of sympathetic-related diseases and support the proposal that the surgical ablation of the CB is useful to restore the autonomic balance and normal cardiorespiratory function in humans. Accordingly, the CB ablation has been used in pilot human studies as a therapeutic treatment for resistant hypertension and HF-induced sympathetic hyperactivity. In this review, I will discuss the supporting evidence for a crucial contribution of the CB in the central autonomic dysfunction and the pros and cons of the CB ablation as a therapy to revert autonomic overactivation. The CB ablation could be a useful method to reverse the enhanced chemoreflex in HF and severe hypertension, but caution is required before extensive use of bilateral CB ablation, which abolished ventilatory responses to hypoxia and may impair baroreceptor function.

Effects of vagotomy on cardiovascular and heart rate variability alterations following chronic normobaric hypoxia in adult rabbits.

BACKGROUND: chronic hypoxia increases basal ventilation and pulmonary vascular resistance, with variable changes in arterial blood pressure and heart rate, but it's impact on heart rate variability and autonomic regulation have been less well examined. We studied changes in arterial blood pressure, heart rate and heart rate variability (HRV) in rabbits subjected to chronic normobaric hypoxia (CNH; PB ~ 719 mmHg; FIO2 ~ 9.2%) for 14 days and assess the effect of autonomic control by acute bilateral vagal denervation. RESULTS: exposure to CNH stalled animal weight gain and increased the hematocrit, without affecting heart rate or arterial blood pressure. Nevertheless, Poincaré plots of the electrocardiographic R-R intervals showed a reduced distribution parallel to the line of identity, which interpreted as reduced long-term HRV. In the frequency domain, CNH reduced the very-low- (< 0.2 Hz) and high-frequency components (> 0.8 Hz) of the R-R spectrograms and produced a prominent component in the low-frequency component (0.2-0.5 Hz) of the power spectrum. In control and CNH exposed rabbits, bilateral vagotomy had no apparent effect on the short- and long-term HRV in the Poincaré plots. However, bilateral vagotomy differentially affected higher-frequency components (> 0.8 Hz); reducing it in control animals without modifying it in CNH-exposed rabbits. CONCLUSIONS: These results suggest that CNH exposure shifts the autonomic balance of heart rate towards a sympathetic predominance without modifying resting heart rate or arterial blood pressure.

Proinflammatory Cytokines in the Nucleus of the Solitary Tract of Hypertensive Rats Exposed to Chronic Intermittent Hypoxia.

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which is considered the main factor for developing hypertension. Sympathetic overflow, oxidative stress and inflammation have been associated with the CIH-induced hypertension. In rats exposed to CIH mimicking OSA, intermittent hypoxia enhanced carotid body (CB) chemosensory discharge, leading to an increase in arterial blood pressure in 3-5 days. In addition, CIH increases the CB levels of proinflammatory cytokines IL-1ß, IL-6 and TNF-α in the CB. Proinflammatory molecules have been also involved in neurogenic hypertension acting on brain cardiovascular centers, like the nucleus of the solitary tract (NTS), which is the primary site for afferent CB inputs. Accordingly, we aim to study if proinflammatory cytokines in the NTS may play a role in the hypertension induced by CIH. Male Sprague-Dawley rats 250 g were exposed to CIH (5% O2, 12 times/h, 8 h/day) for 7-28 days. Brains were removed and processed to measure IL-1ß, IL-6 and TNF-α in the NTS using qPCR and immunofluorescence. The mRNA levels were significantly augmented in the NTS of rats exposed during 21 days to CIH compared with control animals. In addition, a significant increase of IL-1ß, IL-6 and TNF-α immunofluorescence was found in the NTS at day 28 of CIH exposure compared with control rats. Present results suggest that proinflammatory cytokines in the NTS may contribute to the maintenance of hypertension in CIH-exposed animals.

Acute Effects of Systemic Erythropoietin Injections on Carotid Body Chemosensory Activity Following Hypoxic and Hypercapnic Stimulation.

The carotid body (CB) chemoreceptors sense changes in arterial blood gases. Upon stimulation CB chemoreceptors cells release one or more transmitters to excite sensory nerve fibers of the carotid sinus nerve. While several neurotransmitters have been described to contribute to the CB chemosensory process less is known about modulatory molecules. Recent data suggest that erythropoietin (Epo) is involved in the control of ventilation, and it has been shown that Epo receptor is constitutively expressed in the CB chemoreceptors, suggesting a possible role for Epo in regulation of CB function. Therefore, in the present study we aimed to determine whether exogenous applications of Epo modulate the hypoxic and hypercapnic CB chemosensory responses. Carotid sinus nerve discharge was recorded in-situ from anesthetized adult male and female Sprague Dawley rats (350 g, n = 8) before and after systemic administration of Epo (2000 UI/kg). CB-chemosensitivity to hypoxia and hypercapnia was calculated by exposing the rat to FiO2 5-15% and FiCO2 10% gas mixtures, respectively. During baseline recordings at normoxia, we found no effects of Epo on CB activity both in male and female rats. In addition, Epo had no effect on maximal CB response to hypoxia in both male and female rats. Epo injections enhanced the maximum CB chemosensory response to hypercapnia in female rats (before vs. after Epo, 72.5 ± 7.1 Hz vs. 108.3 ± 6.9 Hz, p < 0.05). In contrast, Epo had no effect on maximum CB chemosensory response to hypercapnia in male rats but significantly increased the response recovery times (time required to return to baseline discharge following hypercapnic stimulus) from 2.1 ± 0.1 s to 8.2 ± 2.3 s (p < 0.05). Taken together, our results suggest that Epo has some modulatory effect on the CB chemosensory response to hypercapnia.

Topical Application of Connexin43 Hemichannel Blocker Reduces Carotid Body-Mediated Chemoreflex Drive in Rats.

The carotid body (CB) is the main arterial chemoreceptor involved in oxygen sensing. Upon hypoxic stimulation, CB chemoreceptor cells release neurotransmitters, which increase the frequency of action potentials in sensory nerve fibers of the carotid sinus nerve. The identity of the molecular entity responsible for oxygen sensing is still a matter of debate; however several ion channels have been shown to be involved in this process. Connexin-based ion channels are expressed in the CB; however a definitive role for these channels in mediating CB oxygen sensitivity has not been established. To address the role of these channels, we studied the effect of blockers of connexin-based ion channels on oxygen sensitivity of the CB. A connexin43 (Cx43) hemichannel blocking agent (CHBa) was applied topically to the CB and the CB-mediated hypoxic ventilatory response (FiO2 21, 15, 10 and 5%) was measured in adult male Sprague-Dawley rats (~250 g). In normoxic conditions, CHBa had no effect on tidal volume or respiratory rate, however Cx43 hemichannels inhibition by CHBa significantly impaired the CB-mediated chemoreflex response to hypoxia. CHBa reduced both the gain of the hypoxic ventilatory response (HVR) and the maximum HVR by ~25% and ~50%, respectively. Our results suggest that connexin43 hemichannels contribute to the CB chemoreflex response to hypoxia in rats. Our results suggest that CB connexin43 hemichannels may be pharmacological targets in disease conditions characterized by CB hyperactivity.

Role of Carotid Body in Intermittent Hypoxia-Related Hypertension.

Obstructive sleep apnea (OSA), a common breathing disorder, is recognized as an independent risk factor for systemic hypertension. Among the alterations induced by OSA, the chronic intermittent hypoxia (CIH) is considered the main factor for the hypertension. Exposure of rodents to CIH is the gold-standard method to study the mechanisms involved in the cardiovascular alterations induced by OSA. Although it is well known that CIH produces hypertension, the underlying mechanisms are not totally elucidated. It is likely that the CIH-induced systemic oxidative stress and inflammation may elicit endothelial dysfunction and increase the arterial blood pressure. In addition, OSA patients and animals exposed to CIH show sympathetic hyperactivity and potentiated cardiorespiratory responses to acute hypoxia, suggesting that CIH enhances the peripheral hypoxic chemoreflex. Recent experimental evidences support the proposal that CIH selectively enhances carotid body (CB) chemosensory reactivity to oxygen, which in turn increases sympathetic outflow leading to neurogenic hypertension. In this review, we will discuss the supporting evidence for a critical role of the CB in the generation and maintenance of the hypertension induced by CIH, also, the contribution of oxidative stress to enhance CB chemosensory drive and the activation of sympathetic-related centers in the brain.

Carotid body chemoreceptors, sympathetic neural activation, and cardiometabolic disease.

The carotid body (CB) is the main peripheral chemoreceptor that senses the arterial PO2, PCO2 and pH. In response to hypoxemia, hypercapnia and acidosis, carotid chemosensory discharge elicits reflex respiratory, autonomic and cardiovascular adjustments. The classical construct considers the CB as the main peripheral oxygen sensor, triggering reflex physiological responses to acute hypoxemia and facilitating the ventilatory acclimation to chronic hypoxemia at high altitude. However, a growing body of experimental evidence supports the novel concept that an abnormally enhanced CB chemosensory input to the brainstem contributes to overactivation of the sympathetic nervous system, and consequent pathology. Indeed, the CB has been implicated in several diseases associated with increases in central sympathetic outflow. These include hypertension, heart failure, sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome. Indeed, ablation of the CB has been proposed for the treatment of severe and resistant hypertension in humans. In this review, we will analyze and discuss new evidence supporting an important role for the CB chemoreceptor in the progression of autonomic and cardiorespiratory alterations induced by heart failure, obstructive sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome.

Inflammation and oxidative stress during intermittent hypoxia: the impact on chemoreception.

NEW FINDINGS: What is the topic of this review? This article describes the contribution of oxidative stress and pro-inflammatory cytokines to the enhanced carotid body chemosensory responsiveness to the hypoxia and systemic hypertension induced by chronic intermittent hypoxia. What advances does it highlight? Chronic intermittent hypoxia enhances the carotid body chemosensory discharge during normoxia and hypoxia, leading to sympathetic overactivity and hypertension. New evidence suggests that chronic intermittent hypoxia increases pro-inflammatory cytokines. Here, we discuss the role of inflammation in the alterations of the carotid chemoreceptor function as well as the cardiorespiratory alterations following chronic intermittent hypoxia. Chronic intermittent hypoxia (CIH), the main characteristic of obstructive sleep apnoea, enhances carotid body (CB) chemosensory discharges during normoxia and hypoxia and elicits hypertension. These alterations are attributed to oxidative stress, because antioxidants prevent the enhanced CB chemosensory discharges and the hypertension. In this report, we discuss new evidence supporting the suggestion that oxidative stress-induced upregulation of pro-inflammatory cytokines (i.e. tumour necrosis factor-α and interleukin-1ß) in the CB is involved in the chemosensory potentiation and the hypertension following CIH. Anti-inflammatory treatment with ibuprofen prevents the increased tumour necrosis factor-α and interleukin-1ß levels in the CB and the hypertension, but does not reduce the enhanced chemosensory hypoxic response and the local oxidative stress in the CB. In contrast, antioxidant treatment with ascorbic acid prevents the increase in cytokine concentrations and CB oxidative stress, the chemosensory potentiation and the hypertension. Thus, the enhanced CB chemosensory responses to hypoxia depend critically on the oxidative stress, but not on the increased tumour necrosis factor-α and interleukin-1ß in the CB. We discuss a possible role for pro-inflammatory cytokines in development of the hypertension produced by CIH, acting on cardiorespiratory centres located in the CNS.

Antioxidant and anti hyperglycemic role of wine grape powder in rats fed with a high fructose diet.

BACKGROUND: Metabolic syndrome is a growing worldwide health problem. We evaluated the effects of wine grape powder (WGP), rich in antioxidants and fiber, in a rat model of metabolic syndrome induced by a high fructose diet. We tested whether WGP supplementation may prevent glucose intolerance and decrease oxidative stress in rats fed with a high fructose diet. METHODS: Male Sprague-Dawley rats weighing 180 g were divided into four groups according to their feeding protocols. Rats were fed with control diet (C), control plus 20 % WGP (C + WGP), 50 % high fructose (HF) or 50 % fructose plus 20 % WGP (HF + WGP) for 16 weeks. Blood glucose, insulin and triglycerides, weight, and arterial blood pressure were measured. Homeostasis model assessment (HOMA) index was calculated using insulin and glucose values. A glucose tolerance test was performed 2 days before the end of the experiment. As an index of oxidative stress, thiobarbituric acid reactive substances (TBARS) level was measured in plasma and kidney, and superoxide dismutase was measured in the kidney. RESULTS: Thiobarbituric acid reactive substances in plasma and renal tissue were significantly higher when compared to the control group. In addition, the area under the curve of the glucose tolerance test was higher in HF fed animals. Furthermore, fasting blood glucose, plasma insulin levels, and the HOMA index, were also increased. WGP supplementation prevented these alterations in rats fed with the HF diet. We did not find any significant difference in body weight or systolic blood pressure in any of the groups. CONCLUSIONS: Our results show that WGP supplementation prevented hyperglycemia, insulin resistance and reduced oxidative stress in rats fed with HF diet. We propose that WGP may be used as a supplement in human food as well.

Crucial Role of the Carotid Body Chemoreceptors on the Development of High Arterial Blood Pressure During Chronic Intermittent Hypoxia.

Exposure to chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, produces autonomic and cardiorespirartory alterations, and leads to systemic hypertension. These alterations are associated with enhanced carotid body (CB) chemosensory and ventilatory hypoxic reflexes and a decrease baroreflex (BRS) efficiency. The aim of this study was to determine the therapeutic effect of CB ablation on the elevated arterial blood pressure, the reduced BRS and the potentiated ventilatory response induced by CIH in conscious rats. Arterial blood pressure (BP) was continuous measured by telemetry in male Sprague-Dawley rats exposed to CIH (5 % O(2), 12 times/h, and 8 h/day). After 21 days of CIH, the CBs were selectively cryodestroyed, and rats were kept one more week in CIH. Ventilatory responses to hypoxia were assessed by whole body plethysmography and spontaneous BRS measured by the sequence method. Exposure to CIH produces hypertension, increased the chemoreflex ventilatory hypoxic responses, and decreased BRS. The ablation of the CBs normalized the elevated BP, and the altered ventilatory response and BRS. Present results suggest that the CB play a crucial role in the development of high arterial pressure and autonomic alterations induced by CIH.

Baroreflex and chemoreflex interaction in high-altitude exposure: possible role on exercise performance.

The hypoxic chemoreflex and the arterial baroreflex are implicated in the ventilatory response to exercise. It is well known that long-term exercise training increases parasympathetic and decreases sympathetic tone, both processes influenced by the arterial baroreflex and hypoxic chemoreflex function. Hypobaric hypoxia (i.e., high altitude [HA]) markedly reduces exercise capacity associated with autonomic reflexes. Indeed, a reduced exercise capacity has been found, paralleled by a baroreflex-related parasympathetic withdrawal and a pronounced chemoreflex potentiation. Additionally, it is well known that the baroreflex and chemoreflex interact, and during activation by hypoxia, the chemoreflex is predominant over the baroreflex. Thus, the baroreflex function impairment may likely facilitate the exercise deterioration through the reduction of parasympathetic tone following acute HA exposure, secondary to the chemoreflex activation. Therefore, the main goal of this review is to describe the main physiological mechanisms controlling baro- and chemoreflex function and their role in exercise capacity during HA exposure.