Effect of N-methyl-D-aspartate applied to the ventral surface of the medulla on the trachea

1987 ◽  
Vol 63 (3) ◽  
pp. 1268-1274 ◽  
Author(s):  
M. A. Haxhiu ◽  
E. C. Deal ◽  
M. P. Norcia ◽  
E. van Lunteren ◽  
N. S. Cherniack
Keyword(s):  
Respiratory Activity ◽  
Excitatory Amino Acid ◽  
Ventral Surface ◽  
Intermediate Area ◽  
Cholinergic Antagonist ◽  
Tracheal Pressure ◽  
Area Increase ◽  
Specific Antagonist ◽  
Methyl Nitrate ◽  
Atropine Methyl Nitrate

Structures located near the ventral surface of the medulla (VMS) affect both cardiovascular tone and respiratory activity. In addition cooling the intermediate area of the VMS blocks the increases in parasympathetic activity and tracheal tone resulting from ventilation with hypercapnic or hypoxic gas mixtures, or due to stimulation of mechanoreceptors within the lung. Since cooling the surface of the VMS may affect fibers of passage as well as cell bodies, we performed studies in which pledgets containing N-methyl-D-aspartic acid (NMDA), a synthetic excitatory amino acid, were applied to intermediate area of the VMS. The studies were performed in chloralose-anesthetized, artificially ventilated cats. Application of pledgets containing NMDA (10(-7) mol at 10(-3) M) caused increases in tracheal pressure and the onset of phasic phrenic activity, but application of 10(-8) mol at 10(-4) M of NMDA could produce tracheal constriction without the appearance of phasic phrenic activity. Applying to the entire VMS either 2-amino-5-phosphonovalerate (2-APV, 10(-6) M), a specific antagonist to NMDA, or lidocaine (2%), a local anesthetic, 60 s before the application of pledgets containing NMDA, prevented the increase in tracheal tone and phasic phrenic activity. Intravenous administration of atropine methyl nitrate 0.5 mg/kg, a cholinergic antagonist, blocked tracheal responses to local application of pledgets containing NMDA but did not affect the increase in phasic phrenic nerve activity. These findings suggest that when stimulated, neurons near the surface of the VMS in the vicinity of the intermediate area increase the activity of parasympathetic fibers to the airway.

Influence of the ventral surface of the medulla on tracheal responses to CO2

1986 ◽  
Vol 61 (3) ◽  
pp. 1091-1097 ◽  
Author(s):  
E. C. Deal ◽  
M. A. Haxhiu ◽  
M. P. Norcia ◽  
J. Mitra ◽  
N. S. Cherniack
Keyword(s):  
Motor Activity ◽  
Phrenic Nerve ◽  
Ventral Surface ◽  
Intermediate Area ◽  
Tracheal Pressure ◽  
Cervical Trachea ◽  
Airway Responses ◽  
Airway Tone ◽  
Pressure Changes ◽  
Nerve Discharge

These studies investigated the role of the intermediate area of the ventral surface of the medulla (VMS) in the tracheal constriction produced by hypercapnia. Experiments were performed in chloralose-anesthetized, paralyzed, and artificially ventilated cats. Airway responses were assessed from pressure changes in a bypassed segment of the rostral cervical trachea. Hyperoxic hypercapnia increased tracheal pressure and phrenic nerve activity. Intravenous atropine pretreatment or vagotomy abolished the changes in tracheal pressure without affecting phrenic nerve discharge. Rapid cooling of the intermediate area reversed the tracheal constriction produced by hypercapnia. Graded cooling produced a progressive reduction in the changes in maximal tracheal pressure and phrenic nerve discharge responses caused by hypercapnia. Cooling the intermediate area to 20 degrees C significantly elevated the CO2 thresholds of both responses. These findings demonstrate that structures near the intermediate area of the VMS play a role in the neural cholinergic responses of the tracheal segment to CO2. It is possible that neurons or fibers in intermediate area influence the motor nuclei innervating the trachea. Alternatively, airway tone may be linked to respiratory motor activity so that medullary interventions that influence respiratory motor activity also alter bronchomotor tone.

Respiration during hypothermia: effect of rewarming intermediate areas of ventral medulla

1985 ◽  
Vol 59 (5) ◽  
pp. 1423-1427 ◽  
Author(s):  
J. P. Kiley ◽  
F. L. Eldridge ◽  
D. E. Millhorn
Keyword(s):  
Phrenic Nerve ◽  
Respiratory Activity ◽  
Ventral Surface ◽  
Respiratory Frequency ◽  
Independent Effect ◽  
Neural Function ◽  
Nerve Activity ◽  
Intermediate Area ◽  
Phrenic Nerve Activity ◽  
Significant Reversal

We studied respiration (phrenic nerve activity) during progressive hypothermia to as low as 30.5 degrees C in five anesthetized, paralyzed, glomectomized, and vagotomized cats. PCO2 was maintained at a constant level throughout the experiments. We confirmed the results of a previous study (J. P. Kiley, F. L. Eldridge, and D. E. Millhorn, J. Appl. Physiol. 58: 295–312, 1985) in which respiratory minute output decreased progressively with cooling and respiratory frequency decreased markedly. In addition we show that focal rewarming to normal temperature (37.5 degrees C) of the structures in the intermediate areas on the ventral surface of the medulla resulted in a significant reversal of the depressed respiratory minute activity observed with hypothermia. Respiratory frequency, however, was unaffected by intermediate area rewarming. We conclude that the decreased respiratory activity during hypothermia is due to a generalized interference with neural function. A major portion of these effects is due to cooling of the intermediate areas, but the slowing of respiratory frequency appears to be an independent effect.

Depression of cough reflex by microinjections of antitussive agents into caudal ventral respiratory group of the rabbit

2010 ◽  
Vol 109 (4) ◽  
pp. 1002-1010 ◽  
Author(s):  
Donatella Mutolo ◽  
Fulvia Bongianni ◽  
Elenia Cinelli ◽  
Tito Pantaleo
Keyword(s):  
Receptor Antagonist ◽  
Respiratory Activity ◽  
Neural Substrates ◽  
Cough Reflex ◽  
Ventral Respiratory Group ◽  
Tracheal Pressure ◽  
Site Of Action ◽  
A Site ◽  
Antitussive Agents ◽  
Antitussive Drugs

We have previously shown that the caudal nucleus tractus solitarii is a site of action of some antitussive drugs and that the caudal ventral respiratory group (cVRG) region has a crucial role in determining both the expiratory and inspiratory components of the cough motor pattern. These findings led us to suggest that the cVRG region, and possibly other neural substrates involved in cough regulation, may be sites of action of antitussive drugs. To address this issue, we investigated changes in baseline respiratory activity and cough responses to tracheobronchial mechanical stimulation following microinjections (30–50 nl) of some antitussive drugs into the cVRG of pentobarbital-anesthetized, spontaneously breathing rabbits. [d-Ala2, N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and baclofen at the lower concentrations (0.5 mM and 0.1 mM, respectively) decreased cough number, peak abdominal activity, and peak tracheal pressure and increased cough-related total cycle duration (Tt). At the higher concentrations (5 mM and 1 mM, respectively), both drugs abolished the cough reflex. DAMGO and baclofen also affected baseline respiratory activity. Both drugs reduced peak abdominal activity, while only DAMGO increased Tt, owing to increases in expiratory time. The neurokinin-1 (NK1) receptor antagonist CP-99,994 (10 mM) decreased cough number, peak abdominal activity, and peak tracheal pressure, without affecting baseline respiration. The NK2 receptor antagonist MEN 10376 (5 mM) had no effect. The results indicate that the cVRG is a site of action of some antitussive agents and support the hypothesis that several neural substrates involved in cough regulation may share this characteristic.

Breuer-Hering inflation reflex and breathing pattern in anesthetized humans and cats

1981 ◽  
Vol 51 (5) ◽  
pp. 1162-1168 ◽  
Author(s):  
H. Gautier ◽  
M. Bonora ◽  
J. H. Gaudy
Keyword(s):  
Tidal Volume ◽  
Breathing Pattern ◽  
Respiratory Activity ◽  
Human Subjects ◽  
Threshold Curve ◽  
Ventilatory Pattern ◽  
Tracheal Pressure ◽  
Switch Mechanism

In nine cats and nine human subjects anesthetized with alfaxalone, respiratory activity and tracheal pressure were recorded prior to and during occlusion of the airway at end inspiration or end expiration. Lung inflations at the end of expiration were also performed. In addition, the ventilatory pattern was analyzed during hypercapnia. The results show that occlusions at the end of inspiration or inflations provoked an apnea in both cats and humans. However, concomitant with increases in tidal volume during hypercapnia, inspiratory duration decreased in cats and did not change in human subjects. These results indicate that the Breuer-Hering reflex, which delays the onset of inspiration during inflation was equally operative in cats and humans. In contrast, the “Breuer-Hering threshold curve,” which accounts for the off-switch“ of inspiration was different in cats and humans. Thus, in summary, the Breuer-Hering inflation reflex is operative in human subjects, but it does not seem to be involved in the control of the inspiratory off-switch mechanism during increases respiratory activity resulting from hypercapnia.

Neurotransmitters in the thalamus relaying visceral input to the insular cortex in the rat

2001 ◽  
Vol 281 (5) ◽  
pp. R1665-R1674 ◽  
Author(s):  
Francesco Barnabi ◽  
David F. Cechetto
Keyword(s):  
Amino Acid ◽  
Neuronal Excitability ◽  
Excitatory Amino Acid ◽  
Insular Cortex ◽  
Nmda Antagonist ◽  
Cortical Response ◽  
Evoked Response ◽  
Adrenergic Antagonist ◽  
Before And After ◽  
Specific Antagonist

Neurotransmitters relaying ascending visceral information were examined by comparing the response of neurons in the insular cortex to vagal stimulation (0.8 Hz, 2 mA) before and after neurotransmitter antagonist injections (200 nl) in the ventroposterior parvocellular nucleus of the thalamus (VPpc). Cobalt (10 mM; presynaptic blocker) and kynurenate (100 μM; nonspecific excitatory amino acid antagonist) injections in the VPpc resulted in an attenuation (73–100 and 38–98%, respectively) of the evoked cortical response. Injections of the specific N-methyl-d-aspartate (NMDA) antagonistdl-2-amino-5-phosphonopentanoic acid (200 μM and 2 mM) did not affect the vagally evoked response, whereas the nonspecific non-NMDA antagonist l-glutamic acid diethylester (200 μM) attenuated the vagally evoked response by 66–100%. Three concentrations of thedl-α-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA)-specific antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 and 200 μM and 2 mM) attenuated the vagally evoked cortical response by 29 ± 9, 31 ± 10, and 59 ± 8%, respectively. The more selective AMPA antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (200 μM and 2 mM) inhibited the vagally evoked cortical response by 53 ± 8 and 52 ± 3%, respectively. Phentolamine (0.1 and 1.0 μM), a general α-adrenergic antagonist, and picrotoxin (0.1 and 1.0 μM), a GABAA antagonist, did not affect the vagally evoked response. Atropine, a muscarinic cholinergic antagonist, decreased the vagally evoked response by 40 ± 2% at a concentration of 0.1 μM, but a higher concentration of 1.0 μM had no effect. These results indicate that the non-NMDA excitatory amino acid receptor is necessary for the relay of visceral information in the VPpc. Muscarinic receptors may modulate visceral neuronal excitability in the VPpc, although the exact interaction between the inhibitory (m2) and excitatory (m3 or m5) muscarinic receptor types found in the thalamus is not known.

Nasal and tracheal responses to chemical and somatic afferent stimulation in anesthetized cats

1988 ◽  
Vol 65 (2) ◽  
pp. 870-877 ◽  
Author(s):  
K. P. Strohl ◽  
M. P. Norcia ◽  
A. D. Wolin ◽  
M. A. Haxhiu ◽  
E. van Lunteren ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Stimulation ◽  
Nasal Resistance ◽  
Constant Flow ◽  
Afferent Stimulation ◽  
Intermediate Area ◽  
Tracheal Pressure ◽  
Ventral Medullary Surface ◽  
Nasal Pressure ◽  
Sciatic Nerve Stimulation

Respiratory chemical and reflex interventions have been shown to affect nasal resistance or tracheal tone, respectively. In the present study, nasal caliber (assessed from pressure at a constant flow) and tracheal tone (assessed from pressure in a fluid-filled balloon within an isolated tracheal segment) were monitored simultaneously in anesthetized, paralyzed, artificially ventilated (inspired O2 fraction = 100%) cats. We examined the effect of CO2 inhalation and sciatic nerve stimulation as well as the application of nicotine (6 X 10(-4) mol/l) or lidocaine (2% solution) to the intermediate area of the ventral medullary surface (VMS). CO2 and VMS nicotine resulted in a significant increase in tracheal pressure [147 +/- 73 and 91 +/- 86% (SD), respectively]; and a significant reduction in nasal pressure (-35 +/- 10 and -20 +/- 13%, respectively). In contrast, sciatic nerve stimulation resulted in a significant fall in both tracheal (-50 +/- 36%) and nasal pressure (-21 +/- 13%). Application of 2 or 4% lidocaine to the VMS reduced tracheal pressure but did not significantly affect nasal pressure. After VMS lidocaine, nasal and tracheal responses to CO2, sciatic nerve stimulation, or VMS nicotine, when present, were negligible. These results suggest a role for the VMS in the regulation and coordination of nasal and tracheal caliber responses.

Atropine methyl nitrate inhibits sham feeding in the rat

1978 ◽  
Vol 8 (4) ◽  
pp. 405-407 ◽  
Author(s):  
D. Lorenz ◽  
P. Nardi ◽  
G.P. Smith
Keyword(s):  
Sham Feeding ◽  
Methyl Nitrate ◽  
Atropine Methyl Nitrate

Central effects of somatostatin and atrial natriuretic peptide on tracheal tone

1993 ◽  
Vol 75 (6) ◽  
pp. 2353-2359 ◽  
Author(s):  
M. A. Haxhiu ◽  
E. C. Deal ◽  
E. Van Lunteren ◽  
N. S. Cherniack
Keyword(s):  
Smooth Muscle ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Direct Action ◽  
Ventral Surface ◽  
Arterial Blood ◽  
Inhibitory Pathways ◽  
Tracheal Pressure ◽  
Chemosensitive Areas ◽  
Atrial Natriuretic

The effects of somatostatin and atrial natriuretic peptide applied topically to the ventral surface of the medulla (VMS) on tracheal tone and phrenic nerve activity (Phr) were studied in chloralose-anesthetized and paralyzed cats artificially ventilated with 7% CO2 in O2. Surface application of drugs to the chemosensitive areas of the VMS significantly decreased tracheal tension measured by changes in pressure in a balloon placed in a bypassed segment of the trachea (Ptseg). Application of somatostatin (9 cats) caused a mean decrease in Ptseg from 17.3 +/- 1.8 (SE) to 4.3 +/- 1.4 cmH2O (P < 0.01) and a reduction in Phr from 24.9 +/- 3.4 to 10.3 +/- 3.4 units (P < 0.05). Like somatostatin, application of atrial natriuretic peptide to the VMS (5 cats) produced tracheal relaxation (Ptseg decreased from 19.3 +/- 2.6 to 9.9 +/- 1.3 cmH2O, P < 0.01), but in contrast there was an insignificant reduction in Phr (from 18.5 +/- 3.6 to 16.1 +/- 3.8 units, P > 0.05). When parasympathetic activity was abolished by atropine methylnitrate and tracheal tone was restored with 5-hydroxytryptamine, somatostatin and atrial natriuretic peptide applied on the VMS had no effect on tracheal pressure, suggesting that observed changes were not caused by direct action of peptides on tracheal smooth muscle via the bloodstream or by facilitation of inhibitory pathways. Both somatostatin and atrial natriuretic peptide applications were associated with a slight but significant decrease in arterial blood pressure. These data suggest that somatostatin and atrial natriuretic peptide acting on the chemosensitive structure of the VMS may play significant roles in modulating para-sympathetic outflow to airway smooth muscle.

scholarly journals Heterogeneity of muscarinic receptor-mediated Ca2+ responses in cultured urothelial cells from rat

2008 ◽  
Vol 294 (4) ◽  
pp. F971-F981 ◽  
Author(s):  
F. Aura Kullmann ◽  
D. Artim ◽  
J. Beckel ◽  
S. Barrick ◽  
W. C. de Groat ◽  
...  
Keyword(s):  
Muscarinic Receptors ◽  
Calcium Concentration ◽  
Atp Release ◽  
Urothelial Cells ◽  
Muscarinic Agonists ◽  
Rt Pcr ◽  
Methyl Nitrate ◽  
Atropine Methyl Nitrate ◽  
And Function ◽  
Sensory Mechanisms

Muscarinic receptors (mAChRs) have been identified in the urothelium, a tissue that may be involved in bladder sensory mechanisms. This study investigates the expression and function of mAChRs using cultured urothelial cells from the rat. RT-PCR established the expression of all five mAChR subtypes. Muscarinic agonists acetylcholine (ACh; 10 μM), muscarine (Musc; 20 μM), and oxotremorine methiodide (OxoM; 0.001–20 μM) elicited transient repeatable increases in the intracellular calcium concentration ([Ca2+]i) in ∼50% of cells. These effects were blocked by the mAChR antagonist atropine methyl nitrate (10 μM). The sources of [Ca2+]i changes included influx from external milieu in 63% of cells and influx from external milieu plus release from internal stores in 27% of cells. The use of specific agonists and antagonists (10 μM M1 agonist McN-A-343; 10 μM M2, M3 antagonists AF-DX 116, 4-DAMP) revealed that M1, M2, M3 subtypes were involved in [Ca2+]i changes. The PLC inhibitor U-73122 (10 μM) abolished OxoM-elicited Ca2+ responses in the presence of the M2 antagonist AF-DX 116, suggesting that M1, M3, or M5 mediates [Ca2+]i increases via PLC pathway. ACh (0.1 μM), Musc (10 μM), oxotremorine sesquifumarate (20 μM), and McN-A-343 (1 μM) acting on M1, M2, and M3 mAChR subtypes stimulated ATP release from cultured urothelial cells. In summary, cultured urothelial cells express functional M1, M2, and M3 mAChR subtypes whose activation results in ATP release, possibly through mechanisms involving [Ca2+]i changes.

scholarly journals HCN channels contribute to serotonergic modulation of ventral surface chemosensitive neurons and respiratory activity

2015 ◽  
Vol 113 (4) ◽  
pp. 1195-1205 ◽  
Author(s):  
Virginia E. Hawkins ◽  
Joanna M. Hawryluk ◽  
Ana C. Takakura ◽  
Anastasios V. Tzingounis ◽  
Thiago S. Moreira ◽  
...  
Keyword(s):  
Respiratory Activity ◽  
Ventral Surface ◽  
Hcn Channels ◽  
Inward Current ◽  
Kcnq Channels ◽  
Channel Inhibition ◽  
And Function ◽  
Serotonergic Modulation

Chemosensitive neurons in the retrotrapezoid nucleus (RTN) provide a CO2/H+-dependent drive to breathe and function as an integration center for the respiratory network, including serotonergic raphe neurons. We recently showed that serotonergic modulation of RTN chemoreceptors involved inhibition of KCNQ channels and activation of an unknown inward current. Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels are the molecular correlate of the hyperpolarization-activated inward current ( Ih) and have a high propensity for modulation by serotonin. To investigate whether HCN channels contribute to basal activity and serotonergic modulation of RTN chemoreceptors, we characterize resting activity and the effects of serotonin on RTN chemoreceptors in vitro and on respiratory activity of anesthetized rats in the presence or absence of blockers of KCNQ (XE991) and/or HCN (ZD7288, Cs+) channels. We found in vivo that bilateral RTN injections of ZD7288 increased respiratory activity and in vitro HCN channel blockade increased activity of RTN chemoreceptors under control conditions, but this was blunted by KCNQ channel inhibition. Furthermore, in vivo unilateral RTN injection of XE991 plus ZD7288 eliminated the serotonin response, and in vitro serotonin sensitivity was eliminated by application of XE991 and ZD7288 or SQ22536 (adenylate cyclase blocker). Serotonin-mediated activation of RTN chemoreceptors was blocked by a 5-HT7-receptor blocker and mimicked by a 5-HT7-receptor agonist. In addition, serotonin caused a depolarizing shift in the voltage-dependent activation of Ih. These results suggest that HCN channels contribute to resting chemoreceptor activity and that serotonin activates RTN chemoreceptors and breathing in part by a 5-HT7 receptor-dependent mechanism and downstream activation of Ih.

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