Effect of chronic hypoxia on cholinergic chemotransmission in rat carotid body

He, Long; Dinger, B.; Fidone, S.

doi:10.1152/japplphysiol.00714.2004

Cited by 42 publications

(34 citation statements)

References 33 publications

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“…Levels of arterial CO 2 and/or pH may contribute to these discrepancies between studies, since there is an important depressive effect of the hypocapnia induced by hyperventilation, particularly after chronic hypoxic exposure (1). Because our recordings are poikilocapnic, this may mask the large increase of hypoxic response from the peripheral chemoreceptors observed in rats after chronic hypoxia (18,19). Accordingly, group differences on ventilation after chronic hypoxia as reported in the present study may arise as consequences of changes affecting either the acclimatization and/or desensitization processes to chronic hypoxia.…”

Section: Methodological Considerationsmentioning

confidence: 69%

Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia

Lumbroso¹,

Joseph²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Lumbroso D, Joseph V. Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia. Am J Physiol Regul Integr Comp Physiol 297: R421-R427, 2009. First published June 3, 2009 doi:10.1152/ajpregu.00068.2009.-We tested the hypothesis that neonatal exposure to hypoxia alters acclimatization to chronic hypoxia later in life. Rat pups were exposed to normobaric hypoxia (12% O2; nHx group) in a sealed chamber, or to normoxia (21% O2; nNx group) from the day before birth to postnatal day 10. The animals were then raised in normal conditions until reaching 12 wk of age. At this age, we assessed ventilatory and hematological acclimatization to chronic hypoxia by exposing male and female nHx and nNx rats for 2 wk to 10% O2. Minute ventilation, metabolic rate, hypoxic ventilatory response, hematocrit, and hemoglobin levels were measured both before and after acclimatization. We also quantified right ventricular hypertrophy as an index of pulmonary hypertension both before and after acclimatization. There was a significant effect of neonatal hypoxia that decreases ventilatory response (relative to metabolic rate, V E/V CO2) to acute hypoxia before acclimatization in males but not in females. nHx rats had an impaired acclimatization to chronic hypoxia characterized by altered respiratory pattern and elevated hematocrit and hemoglobin levels after acclimatization, in both males and females. Right ventricular hypertrophy was present before and after acclimatization in nHx rats, indicating that neonatal hypoxia results in pulmonary hypertension in adults. We conclude that neonatal hypoxia impairs acclimatization to chronic hypoxia in adults and may be a factor contributing to the establishment of chronic mountain sickness in humans living at high altitude.hypoxic ventilatory acclimatization; neonatal hypoxia; chronic mountain sickness

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Section: Methodological Considerationsmentioning

confidence: 69%

Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia

Lumbroso¹,

Joseph²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…We have not explored its significance in acclimatization because the capacity of rat chemoreceptor cells to synthesize ACh has been questioned (Gauda et al, 2004), and He et al (2005) showed that blockers of cholinergic receptors were ineffective in inhibiting hypoxia-induced CSN activity in chronically hypoxic rats. Chronic Caffeine Intake in Normoxic Animals.…”

Section: Discussionmentioning

confidence: 99%

Chronic Caffeine Intake in Adult Rat Inhibits Carotid Body Sensitization Produced by Chronic Sustained Hypoxia but Maintains Intact Chemoreflex Output

et al. 2012

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Sustained hypoxia produces a carotid body (CB) sensitization, known as acclimatization, which leads to an increase in carotid sinus nerve (CSN) activity and ensuing hyperventilation greater than expected from the prevailing partial pressure of oxygen. Whether sustained hypoxia is physiological (high altitude) or pathological (lung disease), acclimatization has a homeostatic implication because it tends to minimize hypoxia. Caffeine, the most commonly ingested psychoactive drug and a nonselective adenosine receptor antagonist, alters CB function and ventilatory responses when administered acutely. Our aim was to investigate the effect of chronic caffeine intake on CB function and acclimatization using four groups of rats: normoxic, caffeine-treated normoxic, chronically hypoxic (12% O 2 , 15 days), and caffeine-treated chronically hypoxic rats. Caffeine was administered in drinking water (1 mg/ml). Caffeine ameliorated ventilatory responses to acute hypoxia in normoxic animals without altering the output of the CB (CSN neural activity). Caffeine-treated chronically hypoxic rats exhibited a decrease in the CSN response to acute hypoxia tests but maintained ventilation compared with chronically hypoxic animals. The findings related to CSN neural activity combined with the ventilatory responses indicate that caffeine alters central integration of the CB input to increase the gain of the chemoreflex and that caffeine abolishes CB acclimatization. The putative mechanisms involved in sensitization and its loss were investigated: expression of adenosine receptors in CB (A 2B ) was downregulated and that in petrosal ganglion (A 2A ) was up-regulated in caffeine-treated chronically hypoxic rats; both adenosine and dopamine release from CB chemoreceptor cells was increased in chronic hypoxia and in caffeine-treated chronic hypoxia groups.

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“…In a recent study we showed that a common cholinergic antagonist, mecamylamine, blocks ϳ80% of CSN activity evoked by hypoxia in normal carotid body, but even higher concentrations of this drug are ineffective following CH (18). In contrast, purinergic P2 receptor antagonists block more than 50% of the hypoxia evoked response in both normal and CH preparations (16).…”

Section: L988 Asic Expression In Chemoafferent Neuronsmentioning

confidence: 97%

Chronic hypoxia-induced acid-sensitive ion channel expression in chemoafferent neurons contributes to chemoreceptor hypersensitivity

Liu

Dinger

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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Liu X, He L, Dinger B, Fidone SJ. Chronic hypoxia-induced acid-sensitive ion channel expression in chemoafferent neurons contributes to chemoreceptor hypersensitivity. Am J Physiol Lung Cell Mol Physiol 301: L985-L992, 2011. First published September 2, 2011 doi:10.1152/ajplung.00132.2011.-Previously we demonstrated that chronic hypoxia (CH) induces an inflammatory condition characterized by immune cell invasion and increased expression of inflammatory cytokines in rat carotid body. It is well established that chronic inflammatory pain induces the expression of acid-sensitive ion channels (ASIC) in primary sensory neurons, where they contribute to hyperalgesia and allodynia. The present study examines the effect of CH on ASIC expression in petrosal ganglion (PG), which contains chemoafferent neurons that innervate oxygen-sensitive type I cells in the carotid body. Five isoforms of ASIC transcript were increased ϳ1.5-2.5-fold in PG following exposure of rats to 1, 3, or 7 days of hypobaric hypoxia (380 Torr). ASIC transcript was not increased in the sympathetic superior cervical ganglion (SCG). In the PG, CH also increased the expression of channel-interacting PDZ domain protein, a scaffolding protein known to enhance the surface expression and the low pH-induced current density mediated by ASIC3. Western immunoblot analysis showed that CH elevated ASIC3 protein in PG, but not in SCG or the (sensory) nodose ganglion. ASIC3 transcript was likewise elevated in PG neurons cultured in the presence of inflammatory cytokines. Increased ASIC expression was blocked in CH rats concurrently treated with the nonsteroidal anti-inflammatory drug ibuprofen (4 mg·kg Ϫ1 ·day Ϫ1 ). Electrophysiological recording of carotid sinus nerve (CSN) activity in vitro showed that the specific ASIC antagonist A-317567 (100 M) did not significantly alter hypoxiaevoked activity in normal preparations but blocked ϳ50% of the hypoxic response following CH. Likewise, a high concentration of ibuprofen, which is known to block ASIC1a, reduced hypoxia-evoked CSN activity by ϳ50% in CH preparations. Our findings indicate that CH induces inflammation-dependent phenotypic adjustments in chemoafferent neurons. Following CH, ASIC are important participants in chemotransmission between type I cells and chemoafferent nerve terminals, and these proton-gated channels appear to enhance chemoreceptor sensitivity.

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Effect of chronic hypoxia on cholinergic chemotransmission in rat carotid body

Cited by 42 publications

References 33 publications

Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia

Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia

Chronic Caffeine Intake in Adult Rat Inhibits Carotid Body Sensitization Produced by Chronic Sustained Hypoxia but Maintains Intact Chemoreflex Output

Chronic hypoxia-induced acid-sensitive ion channel expression in chemoafferent neurons contributes to chemoreceptor hypersensitivity

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