Murine Carotid Body Responses to Hypoxia: In vivo Carotid Sinus Nerve Recordings in the DBA/2J and A/J Strains.

AbstractRecent research supports that over-activation of the carotid body plays a key role in metabolic diseases like type 2 diabetes. Supressing carotid body signalling through carotid sinus nerve (CSN) modulation may offer a therapeutic approach for treating such diseases. Here we anatomically and histologically characterised the CSN in the farm pig as a recommended path to translational medicine. We developed an acute in vivo porcine model to assess the application of kilohertz frequency alternating current (KHFAC) to the CSN of evoked chemo-afferent CSN responses. Our results demonstrate the feasibility of this approach in an acute setting, as KHFAC modulation was able to successfully, yet variably, block evoked chemo-afferent responses. The observed variability in blocking response is believed to reflect the complex and diverse anatomy of the porcine CSN, which closely resembles human anatomy, as well as the need for optimisation of electrodes and parameters for a human-sized nerve. Overall, these results demonstrate the feasibility of neuromodulation of the CSN in an anesthetised large animal model, and represent the first steps in driving KHFAC modulation towards clinical translation. Chronic recovery disease models will be required to assess safety and efficacy of this potential therapeutic modality for application in diabetes treatment.

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Effect of Propofol on Carotid Body Chemosensitivity and Cholinergic Chemotransduction

Anesthesiology ◽

10.1097/00000542-200501000-00019 ◽

2005 ◽

Vol 102 (1) ◽

pp. 110-116 ◽

Cited By ~ 23

Author(s):

Malin M. Jonsson ◽

Sten G. E. Lindahl ◽

Lars I. Eriksson

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Carotid Body ◽

Acetylcholine Receptors ◽

Carotid Sinus ◽

Aminobutyric Acid ◽

Receptor Complex ◽

Gamma Aminobutyric Acid ◽

General Anesthetics ◽

Carotid Sinus Nerve

Background Propofol decreases the acute hypoxic ventilatory response in humans and depresses in vivo carotid body chemosensitivity. The mechanisms behind this impaired oxygen sensing and signaling are not understood. Cholinergic transmission is involved in oxygen signaling, and because general anesthetics such as propofol have affinity to neuronal nicotinic acetylcholine receptors, the authors hypothesized that propofol depresses carotid body chemosensitivity and cholinergic signaling. Methods An isolated rabbit carotid body preparation was used. Chemoreceptor activity was recorded from the whole carotid sinus nerve. The effect of propofol on carotid body chemosensitivity was tested at three different degrees of PO2 reduction. Nicotine-induced chemoreceptor response was evaluated using bolus doses of nicotine given before and after propofol 10-500 microM. The contribution of the gamma-aminobutyric acid A receptor complex was tested by addition of gamma-aminobutyric acid A receptor antagonists. Results Propofol reduced carotid body chemosensitivity; the magnitude of depression was dependent on the reduction in PO2. Furthermore, propofol caused a concentration-dependent (10-500 microM) depression of nicotine-induced chemoreceptor response, with a 50% inhibitory concentration (propofol) of 40 microM. Bicuculline in combination with propofol did not have any additional effect, whereas addition of picrotoxin gave a slightly more pronounced inhibition. Conclusions It is concluded that propofol impairs carotid body chemosensitivity, the magnitude of depression being dependent on the severity of PO2 reduction, and that propofol causes a concentration-dependent block of cholinergic chemotransduction via the carotid sinus nerve, whereas it seems unlikely that an activation of the gamma-aminobutyric acid A receptor complex is involved in this interaction.

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Autoradiographic Studies on the Effects of Chronic Unilateral Sectioning of a Carotid Sinus Nerve on 5-HT and SP Binding Sites in the Carotid Body and NTS

Chemoreceptors and Chemoreceptor Reflexes ◽

10.1007/978-1-4684-8938-5_44 ◽

1990 ◽

pp. 305-309 ◽

Cited By ~ 2

Author(s):

M. R. Dashwood ◽

D. S. McQueen ◽

M. de Burgh Daly ◽

K. M. Spyer ◽

Y. Evrard

Keyword(s):

Carotid Body ◽

Binding Sites ◽

Carotid Sinus ◽

Carotid Sinus Nerve

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The Effect of Intermittent Carotid Sinus Nerve and Carotid Body Stimulation on Respiratory Output

CHEST Journal ◽

10.1016/s0012-3692(15)32696-9 ◽

1972 ◽

Vol 61 (2) ◽

pp. 44S ◽

Cited By ~ 1

Author(s):

Frederic L. Eldridge

Keyword(s):

Carotid Body ◽

Carotid Sinus ◽

Carotid Sinus Nerve

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Central Modulation of Inspiratory and Expiratory Stimulations of the Carotid Body and Carotid Sinus Nerve

Central Interaction Between Respiratory and Cardiovascular Control Systems ◽

10.1007/978-3-642-67603-1_21 ◽

1980 ◽

pp. 180-187 ◽

Cited By ~ 1

Author(s):

F. L. Eldridge

Keyword(s):

Carotid Body ◽

Carotid Sinus ◽

Carotid Sinus Nerve

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Respiratory responses to aortic and carotid chemoreceptor activation in the dog

Journal of Applied Physiology ◽

10.1152/jappl.1991.70.6.2539 ◽

1991 ◽

Vol 70 (6) ◽

pp. 2539-2550 ◽

Cited By ~ 12

Author(s):

F. A. Hopp ◽

J. L. Seagard ◽

J. Bajic ◽

E. J. Zuperku

Keyword(s):

Electrical Stimulation ◽

Carotid Body ◽

Carotid Sinus ◽

Chemical Stimulation ◽

Respiratory Drive ◽

Carotid Sinus Nerve ◽

Nerve Activity ◽

Respiratory Reflexes ◽

Respiratory Responses ◽

Stimulation Of

Respiratory responses arising from both chemical stimulation of vascularly isolated aortic body (AB) and carotid body (CB) chemoreceptors and electrical stimulation of aortic nerve (AN) and carotid sinus nerve (CSN) afferents were compared in the anesthetized dog. Respiratory reflexes were measured as changes in inspiratory duration (TI), expiratory duration (TE), and peak averaged phrenic nerve activity (PPNG). Tonic AN and AB stimulations shortened TI and TE with no change in PPNG, while tonic CSN and CB stimulations shortened TE, increased PPNG, and transiently lengthened TI. Phasic AB and AN stimulations throughout inspiration shortened TI with no changes in PPNG or the following TE; however, similar phasic stimulations of the CB and CSN increased both TI and PPNG and decreased the following TE. Phasic AN stimulation during expiration decreased TE and the following TI with no change in PPNG. Similar stimulations of the CB and CSN decreased TE; however, the following TI and PPNG were increased. These findings differ from those found in the cat and suggest that aortic chemoreceptors affect mainly phase timing, while carotid chemoreceptors affect both timing and respiratory drive.

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Neurotransmitter mechanisms in the carotid body: absence of ACh in the carotid sinus nerve

Brain Research ◽

10.1016/0006-8993(78)90471-7 ◽

1978 ◽

Vol 140 (2) ◽

pp. 374-377 ◽

Cited By ~ 15

Author(s):

Alan M. Goldberg ◽

Andrea P. Lentz ◽

Roberts S. Fitzgerald

Keyword(s):

Carotid Body ◽

Carotid Sinus ◽

Carotid Sinus Nerve

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Vagal inhibition of respiratory-linked efferent activity in the carotid sinus nerve

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1984.247.4.r681 ◽

1984 ◽

Vol 247 (4) ◽

pp. R681-R686

Author(s):

D. R. Kostreva ◽

G. L. Palotas ◽

J. P. Kampine

Keyword(s):

Carotid Body ◽

Carotid Sinus ◽

Respiratory Rhythm ◽

Systemic Blood Pressure ◽

Carotid Sinus Nerve ◽

Nerve Activity ◽

Efferent Nerve ◽

Efferent Activity ◽

Central Origin ◽

Spontaneously Breathing

The hypothesis tested in this study was that glossopharyngeal efferent nerve activity coursing through the carotid sinus nerve has a central origin. Efferent activity in the carotid sinus nerve exhibited a respiratory rhythm in spontaneously breathing, closed-chest, mongrel dogs anesthetized with pentobarbital sodium (30 mg/kg iv). Carotid sinus nerve activity was recorded from the intact or cut central end of the carotid sinus nerve. Diaphragm electromyogram (D-EMG), carotid sinus pressure, systemic blood pressure, and electrocardiogram were also recorded. Before vagotomy, small increases in carotid sinus efferent nerve activity (CSENA) synchronous with increases in the D-EMG were observed during spontaneous inspiration. Section of the contralateral cervical vagosympathetic trunk markedly potentiated the increases in CSENA. Bilateral superior cervical ganglionectomy or nodose ganglionectomy failed to alter the increases in CSENA. Section of the ipsilateral glossopharyngeal nerve near the skull abolished the CSENA. This study demonstrates that respiratory-modulated glossopharyngeal efferents course through the carotid sinus nerve to the carotid sinus or carotid body. These efferents may be part of a central respiratory regulatory mechanism that may rapidly alter the sensitivity of the carotid sinus baroreceptors and/or carotid body receptors on a breath-to-breath basis.

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