Recent advances in understanding the physiology of hypoxic sensing by the carotid body

Prabhakar, Nanduri R.; Peng, Yingjie; Nanduri, Jayasri

doi:10.12688/f1000research.16247.1

Cited by 25 publications

(17 citation statements)

References 48 publications

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“…Wild-type and genetically-engineered mice are widely used to understand the mechanisms by which hypoxic challenges elicit carotid body-dependent and -independent ventilatory responses (He et al, 2000(He et al, , 2002(He et al, , 2003Kline and Prabhakar, 2000;Pérez-García et al, 2004;Kline et al, 2005;Pichard et al, 2015;Gao et al, 2017;Wang et al, 2017;Ortega-Sáenz et al, 2018;Peng et al, 2018;Prabhakar et al, 2018). The morphology, neurophysiology and neuropharmacology of the mouse CSC-SCG has received considerable investigation over the years (Black et al, 1972;Yokota and Yamauchi, 1974;Banks and Walter, 1975;Inoue, 1975;Lewis and Burton, 1977;Forehand, 1985;Kidd and Heath, 1988;Gibbins, 1991;Kasa et al, 1991;Little and Heath, 1994;Jobling and Gibbins, 1999;El-Fadaly and Kummer, 2003;David et al, 2010;Cadaveira-Mosquera et al, 2012;Pashai et al, 2012;Alberola-Die et al, 2013;Liu and Bean, 2014;Martinez-Pinna et al, 2018;Mitsuoka et al, 2018;Feldman-Goriachnik and Hanani, 2019;Simeone et al, 2019;Rivas-Ramírez et al, 2020).…”

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confidence: 99%

Loss of Cervical Sympathetic Chain Input to the Superior Cervical Ganglia Affects the Ventilatory Responses to Hypoxic Challenge in Freely-Moving C57BL6 Mice

et al. 2021

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The cervical sympathetic chain (CSC) innervates post-ganglionic sympathetic neurons within the ipsilateral superior cervical ganglion (SCG) of all mammalian species studied to date. The post-ganglionic neurons within the SCG project to a wide variety of structures, including the brain (parenchyma and cerebral arteries), upper airway (e.g., nasopharynx and tongue) and submandibular glands. The SCG also sends post-ganglionic fibers to the carotid body (e.g., chemosensitive glomus cells and microcirculation), however, the function of these connections are not established in the mouse. In addition, nothing is known about the functional importance of the CSC-SCG complex (including input to the carotid body) in the mouse. The objective of this study was to determine the effects of bilateral transection of the CSC on the ventilatory responses [e.g., increases in frequency of breathing (Freq), tidal volume (TV) and minute ventilation (MV)] that occur during and following exposure to a hypoxic gas challenge (10% O2 and 90% N2) in freely-moving sham-operated (SHAM) adult male C57BL6 mice, and in mice in which both CSC were transected (CSCX). Resting ventilatory parameters (19 directly recorded or calculated parameters) were similar in the SHAM and CSCX mice. There were numerous important differences in the responses of CSCX and SHAM mice to the hypoxic challenge. For example, the increases in Freq (and associated decreases in inspiratory and expiratory times, end expiratory pause, and relaxation time), and the increases in MV, expiratory drive, and expiratory flow at 50% exhaled TV (EF50) occurred more quickly in the CSCX mice than in the SHAM mice, although the overall responses were similar in both groups. Moreover, the initial and total increases in peak inspiratory flow were higher in the CSCX mice. Additionally, the overall increases in TV during the latter half of the hypoxic challenge were greater in the CSCX mice. The ventilatory responses that occurred upon return to room-air were essentially similar in the SHAM and CSCX mice. Overall, this novel data suggest that the CSC may normally provide inhibitory input to peripheral (e.g., carotid bodies) and central (e.g., brainstem) structures that are involved in the ventilatory responses to hypoxic gas challenge in C57BL6 mice.

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confidence: 99%

Loss of Cervical Sympathetic Chain Input to the Superior Cervical Ganglia Affects the Ventilatory Responses to Hypoxic Challenge in Freely-Moving C57BL6 Mice

et al. 2021

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“…HO-2 also oxidizes heme to CO and biliverdin, is constitutively expressed in all cells with the promoter responding to glucocorticoids, is a substrate for biliverdin reductase kinase activity, is an oxygen sensor, binds heme to molecules not involved in the catalytic function of the oxygenase, regulates normal cell function, and is important in cellular homeostasis. 24 25 26 27 HO-2 is mainly located in microsomal fractions with HO-1 seen in the microsomal and cytosol fraction. 28 HO-2 activity depends on phosphorylation which is dependent on different protein kinases.…”

Section: P Roduction /R Egulation Of mentioning

confidence: 99%

Cardiac function dependence on carbon monoxide

Mahan

2020

Med Gas Res

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Nitric oxide, studied to evaluate its role in cardiovascular physiology, has cardioprotective and therapeutic effects in cellular signaling, mitochondrial function, and in regulating inflammatory processes. Heme oxygenase (major role in catabolism of heme into biliverdin, carbon monoxide (CO), and iron) has similar effects as well. CO has been suggested as the molecule that is responsible for many of the above mentioned cytoprotective and therapeutic pathways as CO is a signaling molecule in the control of physiological functions. This is counterintuitive as toxic effects are related to its binding to hemoglobin. However, CO is normally produced in the body. Experimental evidence indicates that this toxic gas, CO, exerts cytoprotective properties related to cellular stress including the heart and is being assessed for its cytoprotective and cytotherapeutic properties. While survival of adult cardiomyocytes depends on oxidative phosphorylation (survival and resulting cardiac function is impaired by mitochondrial damage), mitochondrial biogenesis is modified by the heme oxygenase-1/CO system and can result in promotion of mitochondrial biogenesis by associating mitochondrial redox status to the redox-active transcription factors. It has been suggested that the heme oxygenase-1/CO system is important in differentiation of embryonic stem cells and maturation of cardiomyocytes which is thought to mitigate progression of degenerative cardiovascular diseases. Effects on other cardiac cells are being studied. Acute exposure to air pollution (and, therefore, CO) is associated with cardiovascular mortality, myocardial infarction, and heart failure, but changes in the endogenous heme oxygenase-1 system (and, thereby, CO) positively affect cardiovascular health. We will review the effect of CO on heart health and function in this article.

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“…[1][2][3][4][5] Chemosensitive glomus cells within the carotid bodies depolarize in response to decreases in blood pO 2 , increases in blood pCO 2 , and from carbonic anhydrase-catalyzed production of H + ions from increased availability of blood CO 2 . [6][7][8][9][10][11][12][13] Once depolarized, glomus cells release an array of excitatory neurotransmitters [14][15][16][17][18][19][20][21][22][23][24] that trigger action potentials in the nerve terminals of chemoafferents that travel to the nucleus tractus solitarius (NTS) via the carotid sinus nerve (CSN). 6,[8][9][10][11][12] CSN chemoafferent input to the NTS signals a series of downstream cardiorespiratory responses, such as increases in minute ventilation and blood pressure, to restore arterial blood gas homeostasis.…”

Section: Introductionmentioning

confidence: 99%

“…[59][60][61][62][63][64][65][66] Wild-type (WT) mice of various strains and genetically-engineered mice are used to investigate mechanisms by which HCC and HXC elicit ventilatory responses that are dependent and independent of the carotid bodies. 20,21,37,[67][68][69][70][71][72][73][74][75][76][77][78][79][80][81] We reported that the ventilatory responses elicited by a HXC were markedly reduced in freely moving adult male C57BL6 mice with bilateral carotid sinus nerve transections (CSNX). 37 Earlier, Izumizaki et al 51 examineded the involvement of the carotid body-CSN in breathing responses to a hyperoxic (100% O 2 )-hypercapnic (5% CO 2 ) gas challenge in urethaneanesthetized adult male C57BL-6CrSlc mice and found that the ventilatory responses were markedly reduced after bilateral CSNX.…”

Section: Introductionmentioning

confidence: 99%

Ventilatory Responses During and Following Hypercapnic Gas Challenge are Impaired in Male but Not Female Endothelial NOS Knock-out Mice

Getsy

Sundararajan

May

et al. 2021

Preprint

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The roles of endothelial nitric oxide synthase (eNOS) in the ventilatory responses during and after a hypercapnic gas challenge (HCC, 5% CO2, 21% O2, 74% N2) were assessed in freely moving female and male wild-type (WT) C57BL6 mice and eNOS knock-out (eNOS-/-) mice of C57BL6 background. HCC elicited an array of ventilatory responses that were similar in male and female WT mice, such as increases in breathing frequency (with falls in inspiratory and expiratory times), and increases in tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives. eNOS-/- male mice had smaller increases in minute ventilation, peak inspiratory flow and inspiratory drive, and smaller decreases in inspiratory time than WT males. Ventilatory responses in female eNOS-/- mice were similar to those in female WT mice. The ventilatory excitatory phase upon return to room-air was equal in male and female WT mice. However, the post-HCC increases in frequency of breathing (and decreases in inspiratory times), and increases in tidal volume, minute ventilation, inspiratory and expiratory drives, and peak inspiratory and expiratory flows in male eNOS-/- mice were smaller than in male WT mice. In contrast, the post-HCC responses in female eNOS-/- mice were equal to those of the female WT mice. These findings provide the first evidence that the loss of eNOS affects the ventilatory responses during and after HCC in male C57BL6 mice, whereas female C57BL6 mice can compensate for the loss of eNOS, at least in respect to triggering ventilatory responses to HCC.

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Recent advances in understanding the physiology of hypoxic sensing by the carotid body

Cited by 25 publications

References 48 publications

Loss of Cervical Sympathetic Chain Input to the Superior Cervical Ganglia Affects the Ventilatory Responses to Hypoxic Challenge in Freely-Moving C57BL6 Mice

Loss of Cervical Sympathetic Chain Input to the Superior Cervical Ganglia Affects the Ventilatory Responses to Hypoxic Challenge in Freely-Moving C57BL6 Mice

Cardiac function dependence on carbon monoxide

Ventilatory Responses During and Following Hypercapnic Gas Challenge are Impaired in Male but Not Female Endothelial NOS Knock-out Mice

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