In vitro activation of cyclo‐oxygenase in the rabbit carotid body: effect of its blockade on [3H]catecholamine release.

Gomez-Niño, Angela; Almaraz, L.; González, C.

doi:10.1113/jphysiol.1994.sp020128

Cited by 19 publications

(10 citation statements)

References 30 publications

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“…In fact, numerous studies have demonstrated the involvement of selected prostaglandins in the development of nociceptor hyperexcitability in inflamed skin (37). It is relevant that previous studies of normal rabbit carotid body showed that acute hypoxia elicits release of PGE 2 , whereas inhibition of PGE 2 synthesis with indomethacin augmented type I cell activity as indicated by increased release of catecholamine (12,13). These findings indicate that PGE 2 promotes an inhibitory effect on type I cells in acute hypoxia.…”

Section: Discussionmentioning

confidence: 63%

Adaptation to chronic hypoxia involves immune cell invasion and increased expression of inflammatory cytokines in rat carotid body

Liu¹,

He²,

Stensaas³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

108

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Liu X, He L, Stensaas L, Dinger B, Fidone S. Adaptation to chronic hypoxia involves immune cell invasion and increased expression of inflammatory cytokines in rat carotid body. Am J Physiol Lung Cell Mol Physiol 296: L158 -L166, 2009. First published October 31, 2008 doi:10.1152/ajplung.90383.2008.-Exposure to chronic hypoxia (CH; 3-28 days at 380 Torr) induces adaptation in mammalian carotid body such that following CH an acute hypoxic challenge elicits an abnormally large increase in carotid sinus nerve impulse activity. The current study examines the hypothesis that CH initiates an immune response in the carotid body and that chemoreceptor hyperexcitability is dependent on the expression and action of inflammatory cytokines. CH resulted in a robust invasion of ED1 ϩ macrophages, which peaked on day 3 of exposure. Gene expression of proinflammatory cytokines, IL-1␤, TNF␣, and the chemokine, monocyte chemoattractant protein-1, was increased Ͼ2-fold after 1 day of hypoxia followed by a Ͼ2-fold increase in IL-6 on day 3. After 28 days of CH, IL-6 remained elevated Ͼ5-fold, whereas expression of other cytokines recovered to normal levels. Cytokine expression was not restricted to immune cells. Studies of cultured type I cells harvested following 1 day of in vivo hypoxia showed elevated transcript levels of inflammatory cytokines. In situ hybridization studies confirmed expression of IL-6 in type I cells and also showed that CH induces IL-6 expression in supporting type II cells. Concurrent treatment of CH rats with anti-inflammatory drugs (ibuprofen or dexamethasone) blocked immune cell invasion and severely reduced CH-induced cytokine expression in carotid body. Drug treatment also blocked the development of chemoreceptor hypersensitivity in CH animals. Our findings indicate that chemoreceptor adaptation involves novel neuroimmune mechanisms, which may alter the functional phenotypes of type I cells and chemoafferent neurons. dexamethasone; interleukin-1␤; interleukin-6; tumor necrosis factor-␣ THE MAMMALIAN CAROTID BODY consists of integrated units of chemoreceptor, neural, glial, and vascular cells surrounded by connective tissue, which collectively constitute a highly adaptive chemosensory organ. Stimulus transduction occurs in paracrine type I (chemoreceptor) cells, which release multiple neuroactive agents in response to hypoxia, hypercapnia, and acidosis. Primary afferent neurons in the petrosal ganglia project axons through the carotid sinus nerve (CSN) to form synaptic terminals on type I cells, whereas glial-like type II cells envelop the type I cells and terminal axon enlargements, forming lobules that are embedded in connective tissue penetrated by a microvascular network of highly permeable sinusoidal capillaries. Fibroblasts, resident macrophages, and a small number of mast cells are also present in the tissue together with postganglionic parasympathetic and sympathetic axons (24).Prolonged and continuous exposure of mammals to a low PO 2 environment (i.e., chronic hypoxia; CH) elicits adaptation in...

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Section: Discussionmentioning

confidence: 63%

Adaptation to chronic hypoxia involves immune cell invasion and increased expression of inflammatory cytokines in rat carotid body

Liu¹,

He²,

Stensaas³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

108

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“…In the periphery, both PGs are important inhibitors of sympathetic activity to the carotid body and the heart, and therefore might modulate the peripheral chemoreflex. In rabbits, PGE 2 is an important inhibitor of increased catecholamine release from carotid chemoreceptors during hypoxia [22]. In PGID mice, both PGE 2 and thromboxane are elevated several times above WT basal levels [23].…”

Section: Pathways Influencing Cardiac Premotor Neuronesmentioning

confidence: 99%

“…On the other hand, no study was able to demonstrate if PG release in the central and peripheral nervous systems modulate cardiorespiratory regulation, although receptors for both PGI 2 and PGE 2 are distributed in unique regions of the brainstem and sensory vagal afferents that are important for cardiovascular regulation [21]. It is noteworthy that PG are important modulators of carotid body catecholamine release during hypoxia [22].…”

Section: Introductionmentioning

confidence: 97%

α2-Adrenoreceptor mediated sympathoinhibition of heart rate during acute hypoxia is diminished in conscious prostacyclin synthase deficient mice

Pearson

Shirai

Yokoyama

et al. 2006

Pflugers Arch - Eur J Physiol

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Acute hypoxia increases ventilatory drive in conscious animals, resulting in tachycardia. Sustained hypoxia changes the initial chemoreflex ventilatory increase to secondary ventilatory depression, which then evokes a gradual secondary heart rate (HR) reduction. Prostacyclin (PGI(2)) release is known to potentiate alpha(2)-adrenoreceptor (alpha(2)-AR) mediated inhibition of sympathoactivation during ischaemia and hypoxia. We examined whether alpha(2)-AR mediated sympathoinhibition was responsible for limiting hypoxic heart rate increases during initial sympathoactivation, and subsequent secondary HR depression, and if PGI(2) is required for sympathoinhibition of HR. The responses of unrestrained PGI(2) synthase deficient (PGID) and wild type (WT) mice to acute hypoxia (10% O(2) for 30 min) were investigated by simultaneous telemetry, whole body plethysmography and open-flow respirometry. PGID mice exhibited potentiated .V(E) (p < 0.007) after intraperitoneal vehicle injection (n = 8), but not so HR responses compared to WT mice during sustained hypoxia. Idazoxan (alpha(2)-AR antagonist, i.p. bolus 3 mg/kg) pretreatment did not change hypoxic ventilatory response in either group, but significantly elevated hypoxic HR in WT mice only (p < 0.013). Sodium meclofenamate (cyclooxygenase inhibition, i.p. bolus 25 mg/kg) pretreatment eliminated the potentiated .V(E) of PGID and caused significant basal hypotension that led to a transient hypertensive response to hypoxia. From these results, we suggest that alpha(2)-AR activation is required for coupling HR to central inspiratory drive during acute hypoxia, and that PGI(2) is required to enhance the inhibition of sympathoactivation.

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“…Therefore, it is possible that the primary activation of chemoreceptor cells occurs by a mechanism unrelated to ROS, leading to an increase in [Ca 2þ ] i and to an increase in formation of the lipidic second messengers and ROS, both capable of modulating the ongoing chemoreceptor cell activity. The case for prostaglandin has been proved by Gomez-Niñ o et al 45,46 by showing that hypoxia increases the production of PGE 2 and that this prostaglandin inhibited, in a dose-dependent manner, the Ca 2þ currents and the release of neurotransmitters elicited by hypoxia in chemoreceptor cells. Finally, NADPH oxidase, a multienzymatic complex responsible for the oxidative burst and the genesis of ROS used by phagocytes to destroy bacteria and fungi, has been found to be a very ubiquitous enzymatic complex with several isoforms in many tissues.…”

mentioning

confidence: 96%

Role of Glutathione Redox State in Oxygen Sensing by Carotid Body Chemoreceptor Cells

González¹,

Sanz-Alfayate²,

Obeso³

et al. 2004

Oxygen Sensing

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four electrons transferred per oxidized 5-HT molecule, agreeing with the mechanism proposed for the dominant electrochemical oxidation reaction. 16 In NEB cells, the average (AE SEM) quantal charge of secretory events during hypoxia was 33.1 AE 2.4 fC [n ¼ 157 events from six cells, range 2.3-183 fC (Fig. 7)]. This value was obtained from the time integral of selected spikes with the fast-rising phase and slow decay typical of secretory events occurring at the membrane facing the amperometric electrode. Assuming that one 5-HT molecule contributes an average of four electrons, it is estimated that a single synaptic vesicle or quantum in NEB cells releases an average of 13,000 AE 971 (n ¼ 157; six cells) molecules of 5-HT. 13 High extracellular K þ (50 mM) induced a secretory response similar to that elicited by severe hypoxia. Exocytosis was stimulated in normoxic NEB cells after exposure to tetraethylammonium (20 mM) or 4-aminopyridine (2 mM). Hypoxia-induced secretion was abolished by the nonspecific Ca 2þ channel blocker, Cd 2þ (100 M). Secretion was also largely inhibited by the L-type Ca 2þ channel blocker, nifedipine (2 M), but not by the N-type Ca 2þ channel blocker, !-conotoxin GVIA (1 M). The 5-HT 3 receptor blocker, ICS 205 930, also inhibited secretion from NEB cells under hypoxia. These results suggest that hypoxia stimulates 5-HT secretion from intact NEBs via the inhibition of K þ channels and calcium entry through L-type Ca 2þ channels, as well as by positive feedback activation of 5-HT 3 autoreceptors.

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In vitro activation of cyclo‐oxygenase in the rabbit carotid body: effect of its blockade on [3H]catecholamine release.

Cited by 19 publications

References 30 publications

Adaptation to chronic hypoxia involves immune cell invasion and increased expression of inflammatory cytokines in rat carotid body

Adaptation to chronic hypoxia involves immune cell invasion and increased expression of inflammatory cytokines in rat carotid body

α2-Adrenoreceptor mediated sympathoinhibition of heart rate during acute hypoxia is diminished in conscious prostacyclin synthase deficient mice

Role of Glutathione Redox State in Oxygen Sensing by Carotid Body Chemoreceptor Cells

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