scholarly journals Inhalation of electronic cigarette aerosol induces reflex bronchoconstriction by activation of vagal bronchopulmonary C-fibers

2018 ◽  
Vol 315 (4) ◽  
pp. L467-L475 ◽  
Author(s):  
M. Khosravi ◽  
R. L. Lin ◽  
L.-Y. Lee
Keyword(s):  
Airway Resistance ◽  
Critical Role ◽  
Electronic Cigarette ◽  
Sensory Nerves ◽  
Electrophysiological Recording ◽  
Reflex Mechanism ◽  
C Fibers ◽  
Airway Constriction ◽  
C Fiber ◽  
Single Puff

The electronic cigarette (e-cig) has been suggested as a safer alternative to tobacco cigarettes. However, the health effects of e-cigs on the airways have not been fully investigated. Nicotine, the primary chemical constituent of the e-cig aerosol, has been shown to stimulate vagal bronchopulmonary C-fiber sensory nerves, which upon activation can elicit vigorous pulmonary defense reflexes, including airway constriction. In this study, we investigated the bronchomotor response to e-cig inhalation challenge in anesthetized guinea pigs and the mechanisms involved in regulating these responses. Our results showed that delivery of a single puff of e-cig aerosol into the lung triggered immediately a transient bronchoconstriction that sustained for >2 min. The increase in airway resistance was almost completely abolished by a pretreatment with either intravenous injection of atropine or inhalation of aerosolized lidocaine, suggesting that the bronchoconstriction was elicited by cholinergic reflex mechanism and stimulation of airway sensory nerves was probably involved. Indeed, electrophysiological recording further confirmed that inhalation of e-cig aerosol exerted a pronounced stimulatory effect on vagal bronchopulmonary C-fibers. These effects on airway resistance and bronchopulmonary C-fiber activity were absent when the e-cig aerosol containing zero nicotine was inhaled, indicating a critical role of nicotine. Furthermore, a pretreatment with nicotinic acetylcholine receptor antagonists by inhalation completely prevented the airway constriction evoked by e-cig aerosol inhalation. In conclusion, inhalation of a single puff of e-cig aerosol caused a transient bronchoconstriction that was mediated through cholinergic reflex and triggered by a stimulatory effect of nicotine on vagal bronchopulmonary C-fiber afferents.

Pulmonary chemoreflex sensitivity is enhanced by prostaglandin E2 in anesthetized rats

1995 ◽  
Vol 79 (5) ◽  
pp. 1679-1686 ◽  
Author(s):  
L. Y. Lee ◽  
R. F. Morton
Keyword(s):  
Prostaglandin E2 ◽  
Constant Infusion ◽  
Electrophysiological Recording ◽  
Sprague Dawley ◽  
C Fibers ◽  
Sprague Dawley Rats ◽  
Organ Systems ◽  
C Fiber ◽  
Cardiovascular Depression ◽  
Chemical Irritants

Stimulation of vagal pulmonary C-fiber afferents by chemical irritants is believed to be responsible for eliciting the pulmonary chemoreflex (apnea, bradycardia, and hypotension). This study was carried out in anesthetized Sprague-Dawley rats to determine whether the pulmonary chemoreflex was altered by prostaglandin E2 (PGE2), which is one of the major inflammatory mediators in the lungs and is known to enhance the sensitivity of C-fiber afferents in several other organ systems. Capsaicin injected at a dose just above the stimulation threshold (0.25 or 0.5 microgram/kg i.v.) elicited a very mild respiratory and cardiovascular depression. In sharp contrast, during a constant infusion of PGE2 (1.5 micrograms.kg-1.min-1 i.v.), the same dose of capsaicin triggered a long apnea, with the expiratory duration reaching 843% of the baseline expiratory duration, accompanied by intense bradycardia and hypotension. Similarly, the pulmonary chemoreflex response elicited by a bolus injection of phenyl biguanide (1 or 2 micrograms/kg i.v.) was also greatly augmented by PGE2. These enhanced responses were completely abolished, by a perineural capsaicin treatment of both cervical vagi to selectively block the conduction of C fibers, suggesting the involvement of these afferents. Electrophysiological recording of pulmonary C-fiber afferent activity further supported our conclusion that the sensitivity of these sensory endings to capsaicin challenge was potentiated by PGE2.

Pulmonary chemoreflexes elicited by intravenous injection of lactic acid in anesthetized rats

1996 ◽  
Vol 81 (6) ◽  
pp. 2349-2357 ◽  
Author(s):  
Lu-Yuan Lee ◽  
Robert F. Morton ◽  
Jan M. Lundberg
Keyword(s):  
Lactic Acid ◽  
Intravenous Injection ◽  
Inhibitory Effect ◽  
Electrophysiological Recording ◽  
Vagus Nerves ◽  
C Fibers ◽  
Anesthetized Rats ◽  
C Fiber ◽  
Intense Burst ◽  
Carotid Body Chemoreceptors

Lee, Lu-Yuan, Robert F. Morton, and Jan M. Lundberg.Pulmonary chemoreflexes elicited by intravenous injection of lactic acid in anesthetized rats. J. Appl. Physiol. 81(6): 2349–2357, 1996.—Experiments were carried out to characterize the cardiorespiratory reflex responses to intravenous injection of lactic acid and to determine the involvement of vagal bronchopulmonary C-fiber afferents in eliciting these responses in anesthetized rats. Bolus injection of lactic acid (0.2 mmol/kg iv) immediately elicited apnea, bradycardia, and hypotension, which were then followed by a sustained hyperpnea. The immediate apneic and bradycardiac responses to lactic acid were completely abolished by bilateral vagotomy and were absent when the same dose of lactic acid was injected into the left ventricle. The subsequent hyperpneic response was substantially attenuated by denervation of carotid body chemoreceptors. After a perineural capsaicin treatment of both vagus nerves to block the conduction of C fibers, lactic acid no longer evoked the immediate apnea and bradycardia, whereas the hyperpneic response became more pronounced and sustained, presumably because of the removal of the inhibitory effect on breathing mediated by pulmonary C-fiber activation. Single-unit electrophysiological recording showed that intravenous injection of lactic acid consistently evoked an abrupt and intense burst of discharge from the vagal C-fiber afferent endings in the lungs. In conclusion, the cardiorespiratory depressor responses induced by lactic acid are predominantly elicited by activation of vagal pulmonary C fibers.

Neurophysiological basis for neurogenic-mediated articular cartilage anabolism alteration

2001 ◽  
Vol 280 (1) ◽  
pp. R115-R122 ◽  
Author(s):  
Elvire Gouze-Decaris ◽  
Lionel Philippe ◽  
Alain Minn ◽  
Philippe Haouzi ◽  
Pierre Gillet ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Ex Vivo ◽  
Cartilage Damage ◽  
Intrathecal Injection ◽  
Chronic Administration ◽  
C Fibers ◽  
Glutamatergic Synaptic Transmission ◽  
C Fiber ◽  
Fiber Stimulation ◽  
Neurophysiological Basis

This study was designed to investigate the pathways involved in neurogenic-mediated articular cartilage damage triggered by a nonsystemic distant subcutaneous or intra-articular inflammation. The cartilage damage was assessed 24 h after subcutaneous or intra-articular complete Freund's adjuvant (CFA) injection measuring patellar proteoglycan (PG) synthesis (ex vivo [Na2 35SO4] incorporation) in 96 Wistar rats. Unilateral subcutaneous or intra-articular injection of CFA induced significant decrease (25–29%) in PG synthesis in both patellae. Chronic administration of capsaicin (50 mg · kg−1 · day−1 during 4 days), which blunted the normal response of C fiber stimulation, prevented the bilateral significant decrease in cartilage synthesis. Similarly, intrathecal injection of MK-801 (10 nmol/day during 5 days), which blocked the glutamatergic synaptic transmission at the dorsal horn of signal originating in primary afferent C fibers, eliminated the CFA-induced PG synthesis decrease in both patellae. Chemical sympathectomy, induced by guanethidine (12.5 mg · kg−1 · day−1 during 6 wk), also prevented PG synthesis alteration. Finally, compression of the spinal cord at the T3-T5 level had a similar protective effect on the reduction of [Na2 35SO4] incorporation. It is concluded that the signal that triggers articular cartilage synthesis damage induced by a distant local inflammation 1) is transmitted through the afferent C fibers, 2) makes glutamatergic synaptic connections with the preganglionic neurons of the sympathetic system, and 3) involves spinal and supraspinal pathways.

Differential blockade of cat dorsal root C fibers by various chloride solutions

1972 ◽  
Vol 36 (5) ◽  
pp. 569-583 ◽  
Author(s):  
J. Stovall King ◽  
Don L. Jewett ◽  
Howard R. Sundberg
Keyword(s):  
Hypertonic Saline ◽  
Choline Chloride ◽  
Isotonic Saline ◽  
Chloride Ion ◽  
Content Type ◽  
Persistent Effect ◽  
C Fibers ◽  
C Fiber ◽  
Intrathecal Infusion

✓ A possible mechanism by which intrathecal infusion of partially frozen saline might relieve patients of chronic pain has been studied by applying hypertonic saline to the dorsal rootlets of cats in vitro. The supernatant of partially thawed normal saline was found to be hypertonic. Persistent block of C fibers, detected by a collision method, occurred after the rootlets had been exposed to saline from 500 to 2500 mOsm/L for 15 min followed by 15 min of isotonic saline. Few of the A fibers were blocked by this procedure, but both A and C fibers were blocked when solutions of 3500 mOsm/L were used. Differential blockage of C fibers could also be produced with hypotonic saline and with distilled water. Localized cooling, to 2°C for 25 min, had no persistent effect on C fiber conduction, and when cooling was combined with hypertonic saline there was no potentiation of the differential blockade caused by the saline. Hypertonic solutions of sucrose or sodium nitrate produced no persistent differential block; most A and C fibers recovered. However, choline chloride was as effective as sodium chloride in giving a differential blockade. It seems that chloride ion plays a major role in establishing the persistent C fiber blockade observed when dorsal rootlets are exposed to hypertonic saline.

scholarly journals Disruption of Circadian Rhythms by Ambient Light during Neurodevelopment Leads to Autistic-like Molecular and Behavioral Alterations in Adult Mice

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3314
Author(s):  
Kun Fang ◽  
Dong Liu ◽  
Salil S. Pathak ◽  
Bowen Yang ◽  
Jin Li ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Translational Control ◽  
Pyramidal Neurons ◽  
Critical Role ◽  
Mapk Signaling ◽  
Repetitive Behaviors ◽  
Behavioral Changes ◽  
Circadian Disruption ◽  
Electrophysiological Recording ◽  
Functional Changes

Although circadian rhythms are thought to be essential for maintaining body health, the effects of chronic circadian disruption during neurodevelopment remain elusive. Here, using the “Short Day” (SD) mouse model, in which an 8 h/8 h light/dark (LD) cycle was applied from embryonic day 1 to postnatal day 42, we investigated the molecular and behavioral changes after circadian disruption in mice. Adult SD mice fully entrained to the 8 h/8 h LD cycle, and the circadian oscillations of the clock proteins, PERIOD1 and PERIOD2, were disrupted in the suprachiasmatic nucleus and the hippocampus of these mice. By RNA-seq widespread changes were identified in the hippocampal transcriptome, which are functionally associated with neurodevelopment, translational control, and autism. By western blotting and immunostaining hyperactivation of the mTOR and MAPK signaling pathways and enhanced global protein synthesis were found in the hippocampi of SD mice. Electrophysiological recording uncovered enhanced excitatory, but attenuated inhibitory, synaptic transmission in the hippocampal CA1 pyramidal neurons. These functional changes at synapses were corroborated by the immature morphology of the dendritic spines in these neurons. Lastly, autistic-like animal behavioral changes, including impaired social interaction and communication, increased repetitive behaviors, and impaired novel object recognition and location memory, were found in SD mice. Together, these results demonstrate molecular, cellular, and behavioral changes in SD mice, all of which resemble autistic-like phenotypes caused by circadian rhythm disruption. The findings highlight a critical role for circadian rhythms in neurodevelopment.

scholarly journals Identification of a putative binding site critical for general anesthetic activation of TRPA1

2017 ◽  
Vol 114 (14) ◽  
pp. 3762-3767 ◽  
Author(s):  
Hoai T. Ton ◽  
Thieu X. Phan ◽  
Ara M. Abramyan ◽  
Lei Shi ◽  
Gerard P. Ahern
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Transmembrane Domain ◽  
Halogen Bond ◽  
Critical Role ◽  
Sensory Nerves ◽  
Structural Basis ◽  
General Anesthetics ◽  
General Anesthetic ◽  
Potential Binding

General anesthetics suppress CNS activity by modulating the function of membrane ion channels, in particular, by enhancing activity of GABAA receptors. In contrast, several volatile (isoflurane, desflurane) and i.v. (propofol) general anesthetics excite peripheral sensory nerves to cause pain and irritation upon administration. These noxious anesthetics activate transient receptor potential ankyrin repeat 1 (TRPA1), a major nociceptive ion channel, but the underlying mechanisms and site of action are unknown. Here we exploit the observation that pungent anesthetics activate mammalian but not Drosophila TRPA1. Analysis of chimeric Drosophila and mouse TRPA1 channels reveal a critical role for the fifth transmembrane domain (S5) in sensing anesthetics. Interestingly, we show that anesthetics share with the antagonist A-967079 a potential binding pocket lined by residues in the S5, S6, and the first pore helix; isoflurane competitively disrupts A-967079 antagonism, and introducing these mammalian TRPA1 residues into dTRPA1 recapitulates anesthetic agonism. Furthermore, molecular modeling predicts that isoflurane and propofol bind to this pocket by forming H-bond and halogen-bond interactions with Ser-876, Met-915, and Met-956. Mutagenizing Met-915 or Met-956 selectively abolishes activation by isoflurane and propofol without affecting actions of A-967079 or the agonist, menthol. Thus, our combined experimental and computational results reveal the potential binding mode of noxious general anesthetics at TRPA1. These data may provide a structural basis for designing drugs to counter the noxious and vasorelaxant properties of general anesthetics and may prove useful in understanding effects of anesthetics on related ion channels.

scholarly journals Opposing effects of bronchopulmonary C-fiber subtypes on cough in guinea pigs

2018 ◽  
Vol 314 (3) ◽  
pp. R489-R498 ◽  
Author(s):  
Yang-Ling Chou ◽  
Nanako Mori ◽  
Brendan J. Canning
Keyword(s):  
Citric Acid ◽  
Guinea Pigs ◽  
Respiratory Pattern ◽  
Tracheal Mucosa ◽  
Cough Reflex ◽  
C Fibers ◽  
Selective Agonist ◽  
Nodose Ganglia ◽  
C Fiber ◽  
Opposing Effects

We have addressed the hypothesis that the opposing effects of bronchopulmonary C-fiber activation on cough are attributable to the activation of C-fiber subtypes. Coughing was evoked in anesthetized guinea pigs by citric acid (0.001–2 M) applied topically in 100-µl aliquots to the tracheal mucosa. In control preparations, citric acid evoked 10 ± 1 coughs cumulatively. Selective activation of the pulmonary C fibers arising from the nodose ganglia with either aerosols or continuous intravenous infusion of adenosine or the 5-HT3 receptor-selective agonist 2-methyl-5-HT nearly abolished coughing evoked subsequently by topical citric acid challenge. Delivering adenosine or 2-methyl-5-HT directly to the tracheal mucosa (where few if any nodose C fibers terminate) was without effect on citric acid-evoked cough. These actions of pulmonary administration of adenosine and 2-methyl-5-HT were accompanied by an increase in respiratory rate, but it is unlikely that the change in respiratory pattern caused the decrease in coughing, as the rapidly adapting receptor stimulant histamine also produced a marked tachypnea but was without effect on cough. In awake guinea pigs, adenosine failed to evoke coughing but reduced coughing induced by the nonselective C-fiber stimulant capsaicin. We conclude that bronchopulmonary C-fiber subtypes in guinea pigs have opposing effects on cough, with airway C fibers arising from the jugular ganglia initiating and/or sensitizing the cough reflex and the intrapulmonary C fibers arising from the nodose ganglia actively inhibiting cough upon activation.

Abstract 113: Renal Phenotype of Inwardly Rectifying Potassium Channel Kcnj16 (Kir 5.1) Knockout in the Dahl Salt-Sensitive Rats

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Oleg Palygin ◽  
Vladislav Levchenko ◽  
Daria V Ilatovskaya ◽  
Jessica L Barnett ◽  
Aron M Geurts ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Basolateral Membrane ◽  
Critical Role ◽  
Electrolyte Imbalance ◽  
Electrophysiological Recording ◽  
Resting Membrane Potential ◽  
Electrolyte Balance ◽  
Renal Tubules ◽  
Basolateral Membranes ◽  
Hypokalemic Alkalosis

The inward-rectifying channels play an important role in the control of resting membrane potential and tubular homeostasis in the kidney. Kcnj16 (Kir 5.1) form a heteromeric channel with Kcnj10 (Kir 4.1) at the basolateral membranes of aldosterone-sensitive distal nephron (ASDN); mutations in the human KCNJ10 gene result in SeSAME)/EAST syndrome, a complex disorder that includes salt wasting and hypokalemic alkalosis. To illuminate the importance of Kcnj16 (Kir 5.1) in the context of a disease state in vivo, we generated a Kcnj16 knockout rat model in Dahl salt-sensitive (SS) background by using ZFN technology. ZFN against Kcnj16 caused a 18-bp in-frame deletion that occurred in the second protein transmembrane domain. IHC analysis demonstrated highly specific expression of Kcnj16 on the basolateral membranes of ASDN in the control kidneys of SS rats, which was completely abolished in Kcnj16-/- rats. The electrophysiological recording of K+ channels in the CCD basolateral membrane revealed activity of only homomeric Kcnj10 channels (21 pS channel in Kcnj16-/- rats compared to both 41 and 21 pS channels in SS rats). Thus, these data provide evidence of successful knock out of this protein and consequent degradation of the channel in renal tubules. The Kcnj16-/- knockout in SS rat induces electrolyte imbalance, epileptic seizures and result in changes in development (37% reduction in body and 54% in kidney mass). The mean arterial pressure was significantly lower in Kcnj16-/- compared to SS rats (91.3±1.8 to 104.7±5.5 mmHg) when animals were fed a low salt (0.4%) diet. Knockout of Kcnj16 resulted in hypokalemia (4.25±0.09 vs 2.08±0.12 mmol/L in serum of control vs KO rats), hypermagnesemia (0.49±0.02 vs 0.63±0.01 mmol/L in serum of control vs KO rats), and FSGS. Urea electrolyte balance was also disturbed compared to control animals. Importantly, change of the diet to high salt (4%) caused mortality of KO rats within 1-2 days. These data demonstrate critical role of Kcnj16 channels in renal salt handling and in the development of salt-sensitive hypertension.

Endogenous BK stimulates ischemically sensitive abdominal visceral C fiber afferents through kinin B2 receptors

1994 ◽  
Vol 267 (6) ◽  
pp. H2398-H2406 ◽  
Author(s):  
H. L. Pan ◽  
G. L. Stahl ◽  
S. V. Rendig ◽  
O. A. Carretero ◽  
J. C. Longhurst
Keyword(s):  
Receptor Antagonist ◽  
Impulse Activity ◽  
Discharge Rate ◽  
Visceral Afferents ◽  
C Fibers ◽  
C Fiber ◽  
Hoe 140 ◽  
B2 Receptors ◽  
The Right ◽  
Stimulation Of

Abdominal ischemia and reperfusion reflexly activate the cardiovascular system. In the present study, we evaluated the role of endogenously produced bradykinin (BK) in the stimulation of ischemically sensitive visceral afferents. Single-unit activity of abdominal visceral C fiber afferents was recorded from the right thoracic sympathetic chain of anesthetized cats during 5 min of abdominal ischemia. Abdominal ischemia increased the portal venous plasma BK level from 49 +/- 10 to 188 +/- 66 pg/ml (P < 0.05). Injection of BK (1 microgram/kg ia) into the descending aorta significantly increased impulse activity (0.88 +/- 0.16 impulses/s) of 10 C fibers, whereas a kinin B1-receptor agonist, des-Arg9-BK (1 microgram/kg), did not alter the discharge rate. Inhibition of kininase II activity with captopril (4 mg/kg i.v.) potentiated impulse activity of 14 ischemically sensitive C fibers (0.44 +/- 0.09 vs. precaptopril, 0.33 +/- 0.08 impulses/s; P < 0.05). In addition, a kinin B2-receptor antagonist (NPC-17731; 40 micrograms/kg i.v.) attenuated activity of afferents during ischemia (0.39 +/- 0.08 vs. pre-NPC-17731, 0.72 +/- 0.13 impulses/s; P < 0.05) and eliminated the response of 10 C fibers to BK. Another kinin B2-receptor antagonist, Hoe-140 (30 micrograms/kg iv), had similar inhibitory effects on six other ischemically sensitive C fibers. In 15 separate cats treated with aspirin (50 mg/kg i.v.), Hoe-140 (30 micrograms/kg i.v.) attenuated impulse activity of only 3 of 16 ischemically sensitive C fibers. These data suggest that BK produced during abdominal ischemia contributes to the stimulation of ischemically sensitive visceral C fiber afferents through kinin B2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary C-fibers reflexly increase secretion by tracheal submucosal glands in dogs

1985 ◽  
Vol 58 (3) ◽  
pp. 907-910 ◽  
Author(s):  
H. D. Schultz ◽  
A. M. Roberts ◽  
C. Bratcher ◽  
H. M. Coleridge ◽  
J. C. Coleridge ◽  
...  
Keyword(s):  
Gland Secretion ◽  
Right Atrial ◽  
Vagus Nerves ◽  
C Fibers ◽  
Airway Secretion ◽  
Submucosal Glands ◽  
C Fiber ◽  
Anesthetized Dogs ◽  
The Right ◽  
Stimulation Of

Stimulation of bronchial C-fibers evokes a reflex increase in secretion by tracheal submucosal glands, but the influence of pulmonary C-fibers on tracheal gland secretion is uncertain. In anesthetized dogs with open chests, we sprayed powdered tantalum on the exposed mucosa of a segment of the upper trachea to measure the rate of secretion by submucosal glands. Secretions from the gland ducts caused elevations (hillocks) in the tantalum layer. We counted hillocks at 10-s intervals for 60 s before and 60 s after we injected capsaicin (10–20 micrograms/kg) into the right atrium to stimulate pulmonary C-fiber endings. Right atrial injection of capsaicin increased the rate of hillock formation fourfold, but left atrial injection had no significant effect. The response was abolished by cutting the vagus nerves or cooling them to 0 degree C. We conclude that the reflex increase in tracheal submucosal gland secretion evoked by right atrial injection of capsaicin was initiated as capsaicin passed through the pulmonary vascular bed, and hence that pulmonary C-fibers, like bronchial C-fibers, reflexly increase airway secretion.

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