Anandamide modulates carotid sinus nerve afferent activity via TRPV1 receptors increasing responses to heat

2012 ◽  
Vol 112 (1) ◽  
pp. 212-224 ◽  
Author(s):  
Arijit Roy ◽  
Sravan Mandadi ◽  
Marie-Noelle Fiamma ◽  
Ekaterina Rodikova ◽  
Erin V. Ferguson ◽  
...  
Keyword(s):  
Carotid Body ◽  
Carotid Sinus ◽  
Ex Vivo ◽  
Null Mouse ◽  
Temperature Sensitive ◽  
Carotid Sinus Nerve ◽  
Afferent Activity ◽  
Mild Hyperthermia ◽  
Carotid Bodies ◽  
Trpv1 Receptors

Abnormal respiratory chemosensitivity is implicated in recurrent apnea syndromes, with the peripheral chemoreceptors, the carotid bodies, playing a particularly important role. Previous work suggests that supraphysiological concentrations of the endocannabinoid endovanilloid and TASK channel blocker anandamide (ANA) excite carotid bodies, but the mechanism(s) and physiological significance are unknown. Given that carotid body output is temperature-sensitive, we hypothesized that ANA stimulates carotid body chemosensory afferents via temperature-sensitive vanilloid (TRPV1) receptors. To test this hypothesis, we used the dual-perfused in situ rat preparation to confirm that independent perfusion of carotid arteries with supraphysiological concentrations of ANA strongly excites carotid sinus nerve afferents and that this activity is sufficient to increase phrenic activity. Next, using ex vivo carotid body preparations, we demonstrate that these effects are mediated by TRPV1 receptors, not CB1 receptors or TASK channels: in CB1-null mouse preparations, ANA increased afferent activity across all levels of Po2, whereas in TRPV1-null mouse preparations, the stimulatory effect of ANA was absent. In rat ex vivo preparations, ANA's stimulatory effects were mimicked by olvanil, a nonpungent TRPV1 agonist, and suppressed by the TRPV1 antagonist AMG-9810. The specific CB1 agonist oleamide had no effect. Physiological levels of ANA had no effect alone but increased sensitivity to mild hyperthermia. AMG-9810 blocked ANA's effect on the temperature response. Immunolabeling and RT-PCR demonstrated that TRPV1 receptors are not expressed in carotid body glomus cells but reside in petrosal sensory afferents. Together, these results suggest that ANA plays a physiological role in augmenting afferent responses to mild hyperthermia by activating TRPV1 receptors on petrosal afferents.

Dopamine, sensory discharge, and stimulus interaction with CO2 and O2 in cat carotid body

1998 ◽  
Vol 85 (5) ◽  
pp. 1719-1726 ◽  
Author(s):  
D. G. Buerk ◽  
S. Osanai ◽  
A. Mokashi ◽  
S. Lahiri
Keyword(s):  
Carotid Body ◽  
Carotid Sinus ◽  
Body Tissue ◽  
Initial Increase ◽  
Carotid Sinus Nerve ◽  
Bicarbonate Buffer ◽  
Flow Interruption ◽  
Carotid Bodies ◽  
Proportional Relationship ◽  
Baseline Values

It is hypothesized that carotid body chemosensory activity is coupled to neurosecretion. The purpose of this study was to examine whether there was a correspondence between carotid body tissue dopamine (DA) levels and neuronal discharge (ND) measured from the carotid sinus nerve of perfused cat carotid bodies and to characterize interaction between CO2 and O2 in these responses. ND and tissue DA were measured after changing from normoxic, normocapnic control bicarbonate buffer ([Formula: see text]>120 Torr, [Formula: see text] 25–30 Torr, pH ∼ 7.4) to normoxic hypercapnia ([Formula: see text] 55–57 Torr, pH 7.1–7.2) or to hypoxic solutions ([Formula: see text] 30–35 Torr) with normocapnia ([Formula: see text] 25–30 Torr, pH ∼ 7.4) or hypocapnia ([Formula: see text]10–15 Torr, pH 7.6–7.8). Similar temporal changes for ND and tissue DA were found for all of the stimuli, although there was a much different proportional relationship for normoxic hypercapnia. Both ND and DA increased above baseline values during flow interruption and normocapnic hypoxia, and both decreased below baseline values during hypoxic hypocapnia. In contrast, normoxic hypercapnia caused an initial increase in ND, from a baseline of 175 ± 12 (SE) to a peak of 593 ± 20 impulses/s within 4.6 ± 0.9 s, followed by adaptation, whereas ND declined to 423 ± 20 impulses/s after 1 min. Tissue DA initially increased from a baseline of 17.9 ± 1.2 μM to a peak of 23.2 ± 1.2 μM within 3.0 ± 0.7 s, then declined to 2.6 ± 1.0 μM. The substantial decrease in tissue DA during normoxic hypercapnia was not consistent with the parallel changes in DA with ND that were observed for hypoxic stimuli.

Respiratory responses to aortic and carotid chemoreceptor activation in the dog

1991 ◽  
Vol 70 (6) ◽  
pp. 2539-2550 ◽  
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.

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

1978 ◽  
Vol 140 (2) ◽  
pp. 374-377 ◽  
Author(s):  
Alan M. Goldberg ◽  
Andrea P. Lentz ◽  
Roberts S. Fitzgerald
Keyword(s):  
Carotid Body ◽  
Carotid Sinus ◽  
Carotid Sinus Nerve

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

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.

Carbonic anhydrase in the carotid body and the carotid sinus nerve

1985 ◽  
Vol 82 (6) ◽  
pp. 577-580 ◽  
Author(s):  
R. Rigual ◽  
C. I�iguez ◽  
J. Carreres ◽  
C. Gonzalez
Keyword(s):  
Carbonic Anhydrase ◽  
Carotid Body ◽  
Carotid Sinus ◽  
Carotid Sinus Nerve

Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory activity

2004 ◽  
Vol 96 (3) ◽  
pp. 1236-1242 ◽  
Author(s):  
Ying-Jie Peng ◽  
Nanduri R. Prabhakar
Keyword(s):  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Ex Vivo ◽  
Previous Treatment ◽  
Male Rats ◽  
Sensory Response ◽  
Chronic Intermittent Hypoxia ◽  
Radical Scavenger ◽  
Sprague Dawley ◽  
Carotid Bodies

Reflexes arising from the carotid bodies may play an important role in cardiorespiratory changes evoked by chronic intermittent hypoxia (CIH). In the present study, we examined whether CIH affects the hypoxic sensing ability of the carotid bodies and, if so, by what mechanisms. Experiments were performed on adult male rats (Sprague-Dawley, 250–300 g) exposed to two paradigms of CIH for 10 days: 1) multiple exposures to short durations of intermittent hypoxia per day (SDIH; 15sof5%O2 + 5 min of 21% O2, 9 episodes/h, 8 h/day) and 2) single exposure to longer durations of intermittent hypoxia per day [LDIH; 4 h of hypobaric hypoxia (0.4 atm/day) + 20 h of normoxia]. Carotid body sensory response to graded isocapnic hypoxia was examined in both groups of animals under anesthetized conditions. Hypoxic sensory response was significantly enhanced in SDIH but not in LDIH animals. Similar enhancement in hypoxic sensory response was also elicited in ex vivo carotid bodies from SDIH animals, suggesting that the effects were not secondary to cardiovascular changes. SDIH, however, had no significant effect on the hypercapnic sensory response. The effects of SDIH on the hypoxic sensory response completely reversed after SDIH animals were placed in a normoxic environment for an additional 10 days. Previous treatment with systemic administration of [Formula: see text] radical scavenger prevented SDIH-induced augmentation of the hypoxic sensory response. These results demonstrate that SDIH but not LDIH results in selective augmentation of the hypoxic response of the carotid body and [Formula: see text] radicals play an important role in SDIH-induced sensitization of the carotid body.

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