Nitric oxide (NO) produced within the carotid body (CB) is an inhibitory modulator of hypoxic chemoreception (Chugh et al, 1994; Wang et al., 1994, 1995; Iturriaga et al., 1998). Administration of NO donors and NO gas to the cat CB... more
Nitric oxide (NO) produced within the carotid body (CB) is an inhibitory modulator of hypoxic chemoreception (Chugh et al, 1994; Wang et al., 1994, 1995; Iturriaga et al., 1998). Administration of NO donors and NO gas to the cat CB reduces the chemosensory ...
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Chemistry, Enzyme Inhibitors, Medicine, Cats, Anoxia, and 14 moreNitric oxide, Animals, Experimental, Nitric Oxide Synthase, Carotid Body, Imidazoles, Sodium Cyanide, Nitric oxide donors, Endothelial nitric oxide synthase, Springer Ebooks, Medical and Health Sciences, In Vitro Techniques, Nitric oxide synthase type II, and NG-nitroarginine methyl ester
A major hallmark of obstructive sleep apnea is the potentiation of the carotid body (CB) chemosensory response to acute hypoxia, as result of the chronic intermittent hypoxia (CIH) exposition. Several mechanisms have been involved in this... more
A major hallmark of obstructive sleep apnea is the potentiation of the carotid body (CB) chemosensory response to acute hypoxia, as result of the chronic intermittent hypoxia (CIH) exposition. Several mechanisms have been involved in this CB chemosensory potentiation, but the primary target of CIH remains elusive. In physiological conditions, hypoxia depolarized CB chemoreceptor cells, trigger an increase of intracellular Ca(2+), and the subsequent transmitter's release. Since the depolarization is initiated by the inhibition of a TASK-like K(+) channel, we studied if CIH may increase the amplitude of the hypoxic-induced depolarization in the chemoreceptor cells, due to an enhanced inhibition of the TASK-like current.CBs obtained from adult rats exposed to CIH (5% O2, 12 times/hr for 8 hr/day) for 7 days were acute dissociated, and the membrane potential and TASK-like current were recorded from isolated chemoreceptor cells. Resting membrane properties were not modified by CIH, but the amplitude of the hypoxic-evoked depolarization increases ∼2-fold. The same result was obtained when all the voltage-dependent K(+) currents were pharmacologically blocked. Accordingly, the inhibition of the TASK-like current induced by acute hypoxia (PO(2) ∼5 torr) increased from ∼62% in control cells to ∼96% in the CIH cells.Present results show that acute hypoxic inhibition of TASK-like K(+) channel is potentiated by CIH exposure, suggesting that the enhancing effect of CIH on CB chemosensory responsiveness to hypoxia occurs at the initial step of the oxygen transduction in the CB chemoreceptor cells.
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Carotid body type-I cells respond to acute hypoxia with membrane depolarization and calcium-dependent neurotransmitter release. The inhibition of a TASK-like background potassium channels plays a key role in initiating this response.... more
Carotid body type-I cells respond to acute hypoxia with membrane depolarization and calcium-dependent neurotransmitter release. The inhibition of a TASK-like background potassium channels plays a key role in initiating this response. Chronic hypoxia enhances the carotid body chemosensory responses evoked by acute hypoxia, however the accurate mechanism by which chronic hypoxia increases carotid body reactivity is not clear. Therefore, we investigated the effects of chronic hypoxia upon TASK-like currents in isolated type-I cells. Carotid bodies were excised from anaesthetized newborn Sprague-Dawley rats and dissociated by collagenase-trypsin digestion. Isolated cells were maintained under 5% CO(2) in normoxic (21% O(2)) or hypoxic (1-2% O(2)) environment for 24 and 48 hours. Channel activity (NPo) was recorded using the cell-attached configuration of the patch-clamp technique. In normoxic and 24 hours hypoxic cultured cells, acute hypoxic stimuli decreases NPo approximately 70% with no effects on current amplitude. On the other hand, in cultured cells subjected to 48 hours of hypoxia, NPo decreases near to 90% in response to acute hypoxia. We concluded that continuous hypoxic exposure enhances the TASK-like channel activity inhibition in response to acute hypoxia. Our results provide a potential mechanism by which chronic hypoxia increases carotid body reactivity.
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It is known that oligomycin reduces the oxidative phosphorylation high-energy state or high-energy intermediates by inhibiting the formation of ATP without directly inhibiting electron transport, whereas metabolic uncouplers dissipate the... more
It is known that oligomycin reduces the oxidative phosphorylation high-energy state or high-energy intermediates by inhibiting the formation of ATP without directly inhibiting electron transport, whereas metabolic uncouplers dissipate the high-energy state without net production of ATP. The metabolic hypothesis for O2 chemoreception in the carotid body (CB) predicts that 1) oligomycin should diminish O2 consumption and attenuate O2 chemoreception and 2) uncouplers should reverse the effect of oligomycin by increasing O2 consumption without restoring O2 chemoreception. These predictions were tested by simultaneously measuring CB chemosensory discharge from the sinus nerve and the rate of tissue O2 disappearance (dPO2/dt) during interruption of perfusate flow in perfused-superfused cat CB preparations (n = 9). O2 consumption was calculated from dPO2/dt. Flow-interruption responses were measured before and after oligomycin (1-microgram bolus) and subsequently after dinitrophenol (50 microM). Chemosensory responses to bolus injections of hypercapnic Tyrode solution, cyanide, or nicotine were also tested periodically. Oligomycin diminished dPO2/dt from -2.67 +/- 0.30 to -2.02 +/- 0.19 (SE) Torr/s (P < 0.004, paired t test) and reduced the maximal sensory response from 196 +/- 43 to 124 +/- 12 impulses/s (P < 0.002, paired t test) while augmenting the initial response to CO2. Dinitrophenol reversed the metabolic depressant effect of oligomycin but further suppressed the chemosensory response. These results confirm the above predictions and strengthen the metabolic hypothesis for O2 chemoreception in the CB.
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1. Adv Exp Med Biol. 2001;499:55-60. The excitatory effect of nitric oxide on carotid body chemoreception is blocked by oligomycin. Iturriaga R, Mosqueira M. Laboratorio de Neurobiologia, Facultad de Ciencias Biológicas, P. Universidad... more
1. Adv Exp Med Biol. 2001;499:55-60. The excitatory effect of nitric oxide on carotid body chemoreception is blocked by oligomycin. Iturriaga R, Mosqueira M. Laboratorio de Neurobiologia, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago. ...
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The current model of chemoreception in the carotid body (CB) recognizes the glomus cell as the site of transduction of O2, CO2 and [H+] stimuli. In response to hypoxia or acid hypercapnia, glomus cells are expected to release a... more
The current model of chemoreception in the carotid body (CB) recognizes the glomus cell as the site of transduction of O2, CO2 and [H+] stimuli. In response to hypoxia or acid hypercapnia, glomus cells are expected to release a neurotransmitter which in turn should increase the firing rate of chemosensory discharges. Consequently, the chemosensory discharges recorded from the carotid sinus nerve could be used to monitor the cellular responses of the chemoreceptor cells.
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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... more
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. image
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The mechanism of O2 chemoreception in the carotid body (CB) is not clear. Previously, we provided evidence (Mulligan et al., 1981; Mulligan & Lahiri, 1982; Shirahata et al., 1987) that inhibitors of mitochondrial oxidative... more
The mechanism of O2 chemoreception in the carotid body (CB) is not clear. Previously, we provided evidence (Mulligan et al., 1981; Mulligan & Lahiri, 1982; Shirahata et al., 1987) that inhibitors of mitochondrial oxidative phosphorylation specifically blocked the excitatory response to hypoxia. We further demonstrated that it is the energy production rather than O2 consumption alone that is critical. More recently, Duchen and Biscoe (1992) showed similar responses of glomus cell [Ca2+]i to hypoxia. With the discovery of O2 sensitive K+ channels in glomus cells (e.g., Lopez-Barneo et al., 1988; Delpiano and Heschler, 1989), Gonzalez et al. (1992) discounted the metabolic hypothesis of O2 chemoreception. A distinction between the two hypotheses can be made by applying appropriate ratios of CO/O2 to the carotid body and measuring chemosensory and/or glomus cell responses. CO specifically prevents reaction of cytochrome oxidase (Keilin, 1970) with O2 and should manifest a hypoxia-like effect on the one hand, as shown by Joels and Neil (1962), and binding with hemoglobin-like pigment, would behave like O2 and reverse the stimulatory effect of hypoxia, as proposed by Lloyd et al. (1968). We tested these predictions using the cat carotid body perfused and superfused in vitro with cell-free physiological solution and recording the chemosensory responses.
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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... more
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-1β, 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-1β, 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-1β, 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.
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Measurements of oxygen pressures within the carotid body have been of particular importance for elucidating the mechanism(s) of oxygen chemoreception. An optical technique based on the quenching of phosphorescence by oxygen that is... more
Measurements of oxygen pressures within the carotid body have been of particular importance for elucidating the mechanism(s) of oxygen chemoreception. An optical technique based on the quenching of phosphorescence by oxygen that is capable of imaging oxygen within the microvasculature has been developed (Rumsey et al, 1988, Wilson et al, 1991). These optical measurements are non-invasive and in particular have the advantage of determining oxygen pressures throughout the entire tissue. We have previously applied this technology to the study of the isolated perfused/superfused cat carotid body and oxygen chemoreception (Rumsey et al, 1991), relying primarily on imaging of phosphorescence intensity. Although the latter is quite useful for following dynamic changes in oxygen pressures, calculation of oxygen pressure is only qualitative. In addition, the carotid body was perfused and superfuised with cell-free media (Iturriaga et al, 1991). In the present report, we describe measurements of oxygen pressure determined from images in phosphorescence lifetimes (Wilson et al, 1991) in the cat carotid body using an in vivo preparation (Lahiri and DeLaney, 1975). These determinations were compared to those obtained previously with the in vitro preparation, thereby permitting comparison of the oxygenation of this organ in the presence and absence of blood, respectively. In both cases, chemosensory discharge was recorded in order to provide measurements of the expression of oxygen chemoreception.
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Cardiology, Medicine, Cats, Biological Sciences, Heart rate variability, and 14 moreInternal Medicine, Anoxia, Blood Pressure, Chronic Disease, Animals, Male, Heart rate, American, Intermittent hypoxia, Time Factors, Baroreflex, Time varying, Blood pressure variability, and Medical and Health Sciences
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The autonomic nervous system (ANS) plays an important role in the coordination of several physiological functions including sleep/wake process. Significant changes in ANS activity occur during wake-to-sleep transition maintaining the... more
The autonomic nervous system (ANS) plays an important role in the coordination of several physiological functions including sleep/wake process. Significant changes in ANS activity occur during wake-to-sleep transition maintaining the adequate cardiorespiratory regulation and brain activity. Since sleep is a complex homeostatic function, partly regulated by the ANS, it is not surprising that sleep disruption trigger and/or evidence symptoms of ANS impairment. Indeed, several studies suggest a bidirectional relationship between impaired ANS function (i.e. enhanced sympathetic drive), and the emergence/development of sleep disorders. Furthermore, several epidemiological studies described a strong association between sympathetic-mediated diseases and the development and maintenance of sleep disorders resulting in a vicious cycle with adverse outcomes and increased mortality risk. However, which and how the sleep/wake control and ANS circuitry becomes affected during the progression of A...
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Calcium signaling is key for the contraction, differentiation, and proliferation of pulmonary arterial smooth muscle cells. Furthermore, calcium influx through store-operated channels (SOCs) is particularly important in the... more
Calcium signaling is key for the contraction, differentiation, and proliferation of pulmonary arterial smooth muscle cells. Furthermore, calcium influx through store-operated channels (SOCs) is particularly important in the vasoconstrictor response to hypoxia. Previously, we found a decrease in pulmonary hypertension and remodeling in normoxic newborn lambs partially gestated under chronic hypoxia, when treated with 2-aminoethyldiphenyl borinate (2-APB), a non-specific SOC blocker. However, the effects of 2-APB are unknown in neonates completely gestated, born, and raised under environmental hypoxia. Accordingly, we studied the effects of 2-APB-treatment on the cardiopulmonary variables in lambs under chronic hypobaric hypoxia. Experiments were done in nine newborn lambs gestated, born, and raised in high altitude (3,600 m): five animals were treated with 2-APB [intravenous (i.v.) 10 mg kg–1] for 10 days, while other four animals received vehicle. During the treatment, cardiopulmona...
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Obstructive sleep apnea (OSA), a breathing disorder characterized by episodes of chronic intermittent hypoxia (CIH) and re‐oxygenation during sleep, is an independent risk for systemic hypertension. Furtheremore, 20–60% of OSA patients... more
Obstructive sleep apnea (OSA), a breathing disorder characterized by episodes of chronic intermittent hypoxia (CIH) and re‐oxygenation during sleep, is an independent risk for systemic hypertension. Furtheremore, 20–60% of OSA patients develop moderate pulmonary hypertension. Rats exposed to CIH developed pulmonary vascular remodeling, but the mechanisms underlaying the vascular remodeling are not well known. Stim‐activated TRP‐CORAI channel (STOC), cationic calcium‐permeable channels, are overexpressed in the lung and plays a key role in the development of pulmonary vascular remodeling in animals exposed to sustained hypoxia. However, whether these channels are involved in the pulmonary vascular remodeling induced by CIH have not been addressed. We studied the time‐course of the vascular pulmonary remodeling and the changes in STOC expression, in a rodent model of OSA. Male Sprague‐Dawley rats (~200g) were exposed for 14 to 28 days to CIH (5% O2, 12 times/h, for 8h). At 14, 21 and ...
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Supplemental Digital Content is available in the text Background and objective: Chronic intermittent hypoxia (CIH), one of the main features of obstructive sleep apnea (OSA), enhances carotid body-mediated chemoreflex and induces... more
Supplemental Digital Content is available in the text Background and objective: Chronic intermittent hypoxia (CIH), one of the main features of obstructive sleep apnea (OSA), enhances carotid body-mediated chemoreflex and induces hypertension and breathing disorders. The carbamylated form of erythropoietin (cEpo) may have beneficial effects as it retains its antioxidant/anti-inflammatory and neuroprotective profile without increasing red blood cells number. However, no studies have evaluated the potential therapeutic effect of cEpo on CIH-related cardiorespiratory disorders. We aimed to determine whether cEpo normalized the CIH-enhanced carotid body ventilatory chemoreflex, the hypertension and ventilatory disorders in rats. Methods: Male Sprague–Dawley rats (250 g) were exposed to CIH (5% O2, 12/h, 8 h/day) for 28 days. cEPO (20 μg/kg, i.p) was administrated from day 21 every other day for one more week. Cardiovascular and respiratory function were assessed in freely moving animals. Results: Twenty-one days of CIH increased carotid body-mediated chemoreflex responses as evidenced by a significant increase in the hypoxic ventilatory response (FiO2 10%) and triggered irregular eupneic breathing, active expiration, and produced hypertension. cEpo treatment significantly reduced the carotid body--chemoreflex responses, normalizes breathing patterns and the hypertension in CIH. In addition, cEpo treatment effectively normalized carotid body chemosensory responses evoked by acute hypoxic stimulation in CIH rats. Conclusion: Present results strongly support beneficial cardiorespiratory therapeutic effects of cEpo during CIH exposure.
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Comparative Study, Medicine, Humans, Bicycling, Blood Pressure, and 15 moreFemale, Journal Article, Male, Heart rate, Clinical Sciences, Middle Aged, Adult, Hand, Isometric Exercise, Exercise Test, Neurosciences, Grip strength, Isometric Contraction, Pharmacology and pharmaceutical sciences, and Hand strength
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... more
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.
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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... more
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.
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: Sustained and intermittent hypoxia produce vasoconstriction, arterial remodeling, and hypertension in the lung. Stromal interaction molecule (STIM)-activated transient receptor potential channels (TRPC) and calcium release-activated... more
: Sustained and intermittent hypoxia produce vasoconstriction, arterial remodeling, and hypertension in the lung. Stromal interaction molecule (STIM)-activated transient receptor potential channels (TRPC) and calcium release-activated calcium channel protein (ORAI) channels (STOC) play key roles in the progression of pulmonary hypertension in pre-clinical models of animals subjected to sustained and intermittent hypoxia. The available evidence supports the theory that oxidative stress and hypoxic inducible factors upregulate and activate STIM-activated TRPC-ORAI Ca2+ channels, contributing to the pulmonary remodeling and hypertension induced by sustained hypoxia. However, less is known about the effects of oxidative stress and hypoxic inducible factors on the modulation of STIM-activated TRPC-ORAI channels following chronic intermittent hypoxia. In this review, we examined the emerging evidence supporting the theory that oxidative stress and hypoxic inducible factors induced by intermittent hypoxia upregulate and activate STIM-activated TRPC-ORAI Ca2+ channels. In addition, we used bioinformatics tools to search public databases for the genes involved in the upregulation of STIMactivated TRPC-ORAI Ca2+ channels and compare the differential gene expression and biological processes induced by intermittent and sustained hypoxia in lung cells.
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Obstructive sleep apnea (OSA), a sleep breathing disorder featured by chronic intermittent hypoxia (CIH), is associate with pulmonary hypertension. Rats exposed to CIH develop lung vascular remodeling and pulmonary hypertension, which... more
Obstructive sleep apnea (OSA), a sleep breathing disorder featured by chronic intermittent hypoxia (CIH), is associate with pulmonary hypertension. Rats exposed to CIH develop lung vascular remodeling and pulmonary hypertension, which paralleled the upregulation of stromal interaction molecule (STIM)-activated TRPC-ORAI Ca2+ channels (STOC) in the lung, suggesting that STOC participate in the pulmonary vascular alterations. Accordingly, to evaluate the role played by STOC in pulmonary hypertension we studied whether the STOC blocker 2-aminoethoxydiphenyl borate (2-APB) may prevent the vascular remodeling and the pulmonary hypertension induced by CIH in a rat model of OSA. We assessed the effects of 2-APB on right ventricular systolic pressure (RVSP), pulmonary vascular remodeling, α-actin and proliferation marker Ki-67 levels in pulmonary arterial smooth muscle cells (PASMC), mRNA levels of STOC subunits, and systemic and pulmonary oxidative stress (TBARS) in male Sprague-Dawley (20...
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You might find this additional info useful...This article cites 54 articles, 31 of which can be accessed free at:http://ajpregu.physiology.org/content/295/1/R28.full.html#ref-list-1 This article has been cited by 1 other HighWire hosted... more
You might find this additional info useful...This article cites 54 articles, 31 of which can be accessed free at:http://ajpregu.physiology.org/content/295/1/R28.full.html#ref-list-1 This article has been cited by 1 other HighWire hosted articles€[Abstract] [Full Text] [PDF] Eur Respir J, July, 2010; 36 (1): 143-150.R Del Rio, E A Moya and R IturriagaCarotid body and cardiorespiratory alterations in intermittent hypoxia: the oxidative linkUpdated information and services including high resolution figures, can be found at:http://ajpregu.physiology.org/content/295/1/R28.full.html and Comparative Physiology can be found at:Additional material and information about American Journal of Physiology - Regulatory, Integrativehttp://www.the-aps.org/publications/ajpreguThis infomation is current as of February 28, 2011.€
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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... more
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-1β, 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-1β, 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-1β, 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.
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We tested the hypothesis that nitric oxide (NO) produced within the carotid body is a tonic inhibitor of chemoreception and determined the contribution of neuronal and endothelial nitric oxide synthase (eNOS) isoforms to the inhibitory NO... more
We tested the hypothesis that nitric oxide (NO) produced within the carotid body is a tonic inhibitor of chemoreception and determined the contribution of neuronal and endothelial nitric oxide synthase (eNOS) isoforms to the inhibitory NO effect. Accordingly, we studied the effect of NO generated from S-nitroso- N-acetylpenicillamide (SNAP) and compared the effects of the nonselective inhibitor N ω-nitro-l-arginine methyl ester (l-NAME) and the selective nNOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole (TRIM) on chemosensory dose-response curves induced by nicotine and NaCN and responses to hypoxia (Po 2 ≈ 30 Torr). CBs excised from pentobarbitone-anesthetized cats were perfused in vitro with Tyrode at 38°C and pH 7.40, and chemosensory discharges were recorded from the carotid sinus nerve. SNAP (100 μM) reduced the responses to nicotine and NaCN. l-NAME (1 mM) enhanced the responses to nicotine and NaCN by increasing their duration, but TRIM (100 μM) only enhanced the responses...
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... We thank Prof Carlos Eyzaguirre for his comments on this manuscript, and Mrs Carolina Larrain for her help in the preparation of this ... Brain Res 113: 235-253 Zapata P, Larraín C, Iturriaga R, Alcayaga J & Eyzaguirre C... more
... We thank Prof Carlos Eyzaguirre for his comments on this manuscript, and Mrs Carolina Larrain for her help in the preparation of this ... Brain Res 113: 235-253 Zapata P, Larraín C, Iturriaga R, Alcayaga J & Eyzaguirre C (1999) Interactions between acetylcholine and dopamine ...
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Receptor-mediated hydrolysis of membrane-bound inositol phospholipids (1) and choline-containing glycerophospholipids (2) gives rise to diacylglycerol (DAG), which promotes the activity of protein kinase C, an enzyme that relays... more
Receptor-mediated hydrolysis of membrane-bound inositol phospholipids (1) and choline-containing glycerophospholipids (2) gives rise to diacylglycerol (DAG), which promotes the activity of protein kinase C, an enzyme that relays extracellular signals across the membrane to regulate many C2+ -dependent cellular functions (1). For peripheral chemoreceptors, a variety of putative neurotransmitters, administered extravascularly, generate sensory signals. Accordingly, the general assumption is that the neurotransmitters released from the glomus cells as a result of natural stimulus (by an unknown mechanism) presumably act on the receptors on the membrane of the glomus cell and/or sensory nerve endings (3). The receptor binding leads to a specific G-protein dependent activation of phospholipase (phospholipase C for phosphoinositides) and formation of DAG. DAG, in turn, increases the affinity of protein kinase C for C2+, leading to its activation and protein phosphorylation, which controls many physiological functions. Since DAG is rapidly removed, protein kinase C is active only briefly. However, the phosphorylated protein may persist for a longer period and continue to exert physiological functions.