The Role of Arterial Chemoreceptors in Ventilatory Acclimatization to Hypoxia

Bisgard, G. E.

doi:10.1007/978-1-4615-2572-1_10

Cited by 20 publications

(13 citation statements)

References 69 publications

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“…Hypoxia augments the activity of the efferent fibres in the carotid sinus nerve (35), but such activity is unlikely to be a cause of the progressive increase in the chemoreceptor discharge in the VAH, since it is predominately inhibitory to the carotid body (36). Other mechanisms have been considered, but the evidence has been somewhat equivocal, e.g., down-regulation of the inhibitory action of dopamine and a noradrenergic mechanism (30). The results of the present study suggest an alternative explanation based on the observed morphological changes in the carotid body.…”

Section: Discussionmentioning

confidence: 49%

“…Possible significance of morphological changes in the carotid body to acclimatization to chronic hypoxia Exposure to a steady-state chronic hypoxic environment in humans and other species leads to an increase in pulmonary ventilation which is characterised by an immediate increase followed by a time-dependent progressive rise in minute volume and a fall in alveolar and arterial PCO 2 , termed the ventilatory acclimatization to hypoxia (VAH; 29,30). Although the time course of VAH varies between species, the evidence indicates that the carotid body chemoreceptors play an important role in the genesis of VAH (29,30).…”

Section: Discussionmentioning

confidence: 99%

“…Although the time course of VAH varies between species, the evidence indicates that the carotid body chemoreceptors play an important role in the genesis of VAH (29,30). The discharge in the chemoreceptor fibres of the carotid sinus nerve increases with a time course similar to that of pulmonary ventilation (30)(31)(32), and there is a timedependent increased sensitivity of the oxygen-responsive mechanism (33).…”

Section: Discussionmentioning

confidence: 99%

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Quantitative studies of the vasculature of the carotid body in the chronically hypoxic rat

et al. 2000

Braz J Med Biol Res

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The carotid bodies of rats made chronically hypoxic by breathing 12% O 2 in a normobaric chamber (inspired PO 2 91 mmHg) were compared with those of controls. Serial 5-µm sections of the organs were examined using an interactive image analysis system. The total volume of the carotid bodies was increased by 64%. The total vascular volume rose by 103% and was likely due to an increase in size of the large vessels (>12 µm lumen diameter) because the small vessel (5-12 µm lumen diameter) volume did not increase significantly while the small vessel density tended to decrease. The extravascular volume was increased by 57%. Expressed as a percentage of the total volume of the organ, the total vascular volume did not change, but the small vessel volume was significantly decreased from 7.83 to 6.06%. The large vessel volume must therefore have been increased. The proportion occupied by the extravascular volume was virtually unchanged (84 vs 82%). In accordance with these findings, the small vessel endothelial surface area per unit carotid body volume was diminished from 95.2 to 76.5 mm -1 , while the extravascular area per small vessel was increased from 493 to 641 µm 2 or by 30%. In conclusion, the enlargement of the carotid body in chronic hypoxia is most likely due to an increase in total vascular volume, mainly involving the large vessels, and to an increase in extravascular volume. This is in contrast to our previously published findings indicating that in the spontaneous insulin-dependent diabetic rat the enlargement of the carotid body is due solely to an increase in extravascular volume. Some of these data were previously reported in abstract form

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Quantitative studies of the vasculature of the carotid body in the chronically hypoxic rat

et al. 2000

Braz J Med Biol Res

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“…15,16). In view of the fact that CSN discharge is increased on exposure to CH (2,3,31), numerous studies have focused on elucidating adaptive changes in type I cells. Indeed, these efforts demonstrated adjustments in the functional properties of type I cells, including altered membrane currents, as well as changes in the metabolism and actions of endogenous neurotransmitters and neuropeptides (19 -21, 29).…”

mentioning

confidence: 99%

Effect of chronic hypoxia on cholinergic chemotransmission in rat carotid body

Dinger²,

Fidone³

2005

Journal of Applied Physiology

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He, L., B. Dinger, and S. Fidone. Effect of chronic hypoxia on cholinergic chemotransmission in rat carotid body. J Appl Physiol 98: 614 -619, 2005; doi:10.1152/japplphysiol.00714.2004.-Current views suggest that oxygen sensing in the carotid body occurs in chemosensory type I cells, which excite synaptically apposed chemoafferent nerve terminals in the carotid sinus nerve (CSN). Prolonged exposure in a low-oxygen environment [i.e., chronic hypoxia (CH)] elicits an elevated stimulus-evoked discharge in chemoreceptor CSN fibers (i.e., increased chemosensitivity). In the present study, we evaluated cholinergic chemotransmission in the rat carotid body in an effort to test the hypothesis that CH enhances ACh-mediated synaptic activity between type I cells and chemoafferent nerve terminals. Animals were exposed in a hypobaric chamber (barometric pressure ϭ 380 Torr) for 9 -22 days before evaluation of chemoreceptor activity using an in vitro carotid body/CSN preparation. Nerve activity evoked by ACh was significantly larger (P Ͻ 0.01) after CH, suggesting increased expression of cholinergic receptors. Approximately 80% of the CSN impulse activity elicited by ACh (100-or 1,000-g bolus) in both normal and CH preparations was blocked by the specific nicotinic receptor antagonist mecamylamine (100 M). CSN activity elicited by acute hypoxia or hypercapnia in normal preparations was likewise blocked (Ն80%) in the presence of 100 M mecamylamine, but after CH the enhanced CSN activity elicited by acute hypoxia or hypercapnia was not reduced in the presence of 100 or 500 M mecamylamine. A muscarinic receptor antagonist, atropine (10 M), and a specific nicotinic receptor ␣ 7 subunit antagonist, methyllycaconatine (50 nM), blocked ϳ50% of the hypoxia-evoked activity in normal preparations but were ineffective after CH. Prolonged exposure to hypoxia appears to dramatically alter chemotransmission in the carotid body, and may induce alternative neurotransmitter mechanisms and/or electrical coupling between type I cells and chemoafferent nerve terminals.carotid sinus nerve; low-oxygen environment; acetylcholine; hypercapnia CHRONIC EXPOSURE IN A LOW-OXYGEN (O 2 ) environment [i.e., chronic hypoxia (CH)] initiates a multitude of physiological adjustments that tend to mitigate the adverse effects of hypoxia. Among the most important of these adaptive changes is increased ventilation, evident as elevated tidal volume and/or frequency of breathing. CH, lasting for hours or days, initiates a time-dependent increase in breathing known as ventilatory acclimatization to hypoxia (VAH). In rats, VAH progresses over a 4-to 5-day period, and enhanced breathing persists for at least 14 days (25). Attempts to identify the structures that mediate VAH have focused principally on the carotid chemoreflex pathway, which consists of multiple components, including 1) chemoreceptor type I (glomus) cells in the carotid body; 2) chemoafferent neurons of the petrosal ganglion (PG), which innervate the type I cells via the carotid sinus nerve (CSN); 3) a ...

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“…Residing in a low O 2 environment for periods of up to 2 weeks elicits a gradual increase in carotid chemosensitivity, an alteration which likely underlies the well documented ventilatory acclimatization to high altitude [5,6]. Moreover, continuous exposure (i.e., months to years) may eventually blunt chemosensitivity and decrease the hypoxic ventilatory response (HVR) evoked by an acute hypoxic challenge [7,8].…”

Section: Introductionmentioning

confidence: 99%

Protein Phosphorylation Signaling Mechanisms in Carotid Body Chemoreception

Wang

He²,

Chen³

et al. 1999

Biol Signals Recept

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Chemotransduction in the carotid body occurs in specialized type I cells and likely involves a complex series of regulated events which culminates in the release of neurotransmitter agents and the excitation of afferent nerve fibers. Previous studies have shown that multiple factors, including the levels of calcium and cyclic nucleotide second messengers, are important regulators of the chemoreceptor transduction cascade in type I cells. In addition, increases in electrical excitability induced in type I cells by chronic exposure to hypoxia are mimicked by agents which elevate intracellular cyclic AMP levels [Stea et al., J Neurosci 1995;15:2192–2202]. These and other findings suggest that protein kinases, and the phosphorylation of specific protein targets are important components of the hypoxic transduction machinery. Moreover, protein kinase-mediated cascades may participate in the well-known physiological adjustments which occur in the carotid body during prolonged stimulation. In the current study, our data demonstrate (1) the presence of specific protein kinases and target phosphoproteins in the carotid body, and also in the morphologically similar small intensely fluorescent cells of the superior cervical sympathetic ganglia. (2) Nitric oxide production and efferent inhibition in the chemosensory tissue is reduced in the presence of the specific tyrosine kinase inhibitor, lavendustin A. (3) Hypoxia-induced catecholamine release from type I cells is inhibited by the protein kinase A antagonist, Rp-cAMPs. And finally (4), exposure to chronic hypoxia up-regulates the expression of the tyrosine kinase, fyn, and an important growth regulatory phosphoprotein, growth associated protein-43 (GAP-43). These findings suggest that second messenger-mediated phosphorylation and dephosphorylation of specific protein targets is a mechanism capable of regulating diverse cellular functions in the carotid body during acute and chronic stimulation.

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The Role of Arterial Chemoreceptors in Ventilatory Acclimatization to Hypoxia

Cited by 20 publications

References 69 publications

Quantitative studies of the vasculature of the carotid body in the chronically hypoxic rat

Quantitative studies of the vasculature of the carotid body in the chronically hypoxic rat

Effect of chronic hypoxia on cholinergic chemotransmission in rat carotid body

Protein Phosphorylation Signaling Mechanisms in Carotid Body Chemoreception

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