scholarly journals Prostaglandin involvement in lung C-fiber activation by substance P in guinea pigs

2006 ◽  
Vol 100 (6) ◽  
pp. 1918-1927 ◽  
Author(s):  
Dale R. Bergren
Keyword(s):  
Substance P ◽  
Guinea Pigs ◽  
Airway Hyperresponsiveness ◽  
Prostaglandin E ◽  
C Fibers ◽  
Arterial Blood ◽  
C Fiber ◽  
Before And After ◽  
Acid Metabolites ◽  
Series Of Experiments

Airway hyperresponsiveness is a cardinal feature of asthma. Lung C-fiber activation induces central and local defense reflexes that may contribute to airway hyperresponsiveness. Initial studies show that substance P (SP) activates C fibers even though it is produced and released by these same C fibers. SP may induce release of other endogenous mediators. Bradykinin (BK) is an endogenous mediator that activates C fibers. The hypothesis was tested that SP activates C fibers via BK release. Guinea pigs were anesthetized, and C-fiber activity (FA), pulmonary insufflation pressure (PIP), heart rate, and arterial blood pressure were monitored before and after intravenous injection of capsaicin (Cap), SP, and BK. Identical agonist challenges were repeated after infusion of an antagonist cocktail of des-Arg9-[Leu8]-BK (10−3 M, B1 antagonist), and HOE-140 (10−4 M, B2 antagonist). After antagonist administration, BK increased neither PIP nor FA. Increases in neither PIP nor FA were attenuated after Cap or SP challenge. In a second series of experiments, Cap and SP were injected before and after infusion of indomethacin (1 mg/kg iv) to determine whether either agent activates C fibers through release of arachidonic acid metabolites. Indomethacin administration decreased the effect of SP challenge on FA but not PIP. The effect of Cap on FA or PIP was not altered by indomethacin. In subsequent experiments, C fibers were activated by prostaglandin E2 and F2α. Therefore, exogenously applied SP stimulates an indomethacin-sensitive pathway leading to C-fiber activation.

Substance P in the nucleus of the solitary tract augments bronchopulmonary C fiber reflex output

2000 ◽  
Vol 279 (4) ◽  
pp. R1215-R1223 ◽  
Author(s):  
T. Mutoh ◽  
A. C. Bonham ◽  
J. P. Joad
Keyword(s):  
Substance P ◽  
Solitary Tract ◽  
C Fibers ◽  
Arterial Blood ◽  
Tracheal Pressure ◽  
C Fiber ◽  
Before And After ◽  
Neurokinin 1 ◽  
Central Synapses ◽  
Nerve Discharge

Bronchopulmonary C fibers defend the lungs against injury from inhaled agents by a central nervous system reflex consisting of apnea, cough, bronchoconstriction, hypotension, and bradycardia. Glutamate is the putative neurotransmitter at the first central synapses in the nucleus of the solitary tract (NTS), but substance P, also released in the NTS, may modulate the transmission. To test the hypothesis that substance P in the NTS augments bronchopulmonary C fiber input and hence reflex output, we stimulated the C fibers with left atrial capsaicin (LA CAP) injections and compared the changes in phrenic nerve discharge, tracheal pressure (TP), arterial blood pressure (ABP), and heart rate (HR) in guinea pigs before and after substance P injections (200 μM, 25 nl) in the NTS. Substance P significantly augmented LA CAP-evoked increases in expiratory time by 10-fold and increases in TP and decreases in ABP and HR by threefold, effects prevented by neurokinin-1 (NK1) receptor antagonism. Thus substance P acting at NTS NK1 receptors can exaggerate bronchopulmonary C fiber reflex output. Because substance P synthesis in vagal airway C fibers may be enhanced in pathological conditions such as allergic asthma, the findings may help explain some of the associated respiratory symptoms including cough and bronchoconstriction.

Sidestream smoke exposure enhances rapidly adapting receptor responses to substance P in young guinea pigs

1996 ◽  
Vol 81 (4) ◽  
pp. 1715-1722 ◽  
Author(s):  
A. C. Bonham ◽  
K. S. Kott ◽  
J. P. Joad
Keyword(s):  
Substance P ◽  
Tobacco Smoke ◽  
Guinea Pigs ◽  
Airway Hyperresponsiveness ◽  
Chronic Exposure ◽  
Smoke Exposure ◽  
Sidestream Smoke ◽  
Arterial Blood ◽  
Tracheal Pressure ◽  
Neurokinin 1

Bonham, A. C., K. S. Kott, and J. P. Joad. Sidestream smoke exposure enhances rapidly adapting receptor responses to substance P in young guinea pigs. J. Appl. Physiol. 81(4): 1715–1722, 1996.—We determined the effect of sidestream tobacco smoke (SS) exposure on responses of lung rapidly adapting receptors (RARs), peak tracheal pressure (Ptr), and arterial blood pressure (ABP) to substance P in young guinea pigs. Guinea pigs were exposed to SS or filtered air from day 8 to days 41–45 of life. They were then anesthetized and given three doses of intravenous substance P (1.56–4.94 nmol/kg). SS exposure augmented substance P-evoked increases in RAR activity ( P = 0.029 by analysis of variance) but not substance P-evoked increases in peak Ptr or decreases in ABP. Neurokinin 1-receptor blockade (CP-96345, 400 nmol/kg) attenuated substance P-evoked increases in RAR activity ( P = 0.001) and ABP ( P = 0.009) but not in peak Ptr ( P = 0.06). Thus chronic exposure to SS in young guinea pigs exaggerates RAR responsiveness to substance P. The findings may help explain the increased incidence of airway hyperresponsiveness and cough in children chronically exposed to environmental tobacco smoke.

Chronic exposure to sidestream tobacco smoke augments lung C-fiber responsiveness in young guinea pigs

1999 ◽  
Vol 87 (2) ◽  
pp. 757-768 ◽  
Author(s):  
T. Mutoh ◽  
A. C. Bonham ◽  
K. S. Kott ◽  
J. P. Joad
Keyword(s):  
Tobacco Smoke ◽  
Guinea Pigs ◽  
Chronic Exposure ◽  
Dynamic Compliance ◽  
Mechanical Stimuli ◽  
C Fibers ◽  
Arterial Blood ◽  
Baseline Activity ◽  
Tracheal Pressure ◽  
C Fiber

Children chronically exposed to environmental tobacco smoke (ETS) have more coughs, wheezes, and airway obstruction, which may result in part from stimulation of lung C fibers. We examined the effect of chronic exposure to sidestream tobacco smoke (SS, a surrogate for ETS) on lung C-fiber responsiveness in guinea pigs, in which dynamic compliance (Cdyn), lung resistance, tracheal pressure, arterial blood pressure, and heart rate were also monitored. Guinea pigs were exposed to SS (1 mg/mm3 total suspended particulates) or filtered air 5 days/wk from 1 to 6 wk of age. They were then anesthetized, and lung C fibers ( n = 55), identified by a conduction velocity of <2.0 m/s, were tested for responsiveness to chemical and mechanical stimuli. SS exposure doubled C-fiber responsiveness to left atrial capsaicin ( P = 0.02) and lung hyperinflation ( P = 0.03) but had no effect on responsiveness to inhaled capsaicin or bradykinin or on baseline activity. The data indicate that chronically exposing young guinea pigs to SS enhances C-fiber sensitivity to certain stimuli and may help explain respiratory symptoms in children exposed to ETS.

Effect of the NEP inhibitor SCH32615 on airway responses to intravenous substance P in guinea pigs

1992 ◽  
Vol 73 (5) ◽  
pp. 1847-1853 ◽  
Author(s):  
S. A. Shore ◽  
M. A. Martins ◽  
J. M. Drazen
Keyword(s):  
Substance P ◽  
Guinea Pigs ◽  
Ace Inhibitor ◽  
Dynamic Compliance ◽  
Neutral Endopeptidase ◽  
Neurokinin A ◽  
Mechanically Ventilated ◽  
Arterial Blood ◽  
Airway Responses ◽  
Nep Inhibition

We examined the effects of the selective neutral endopeptidase (NEP) inhibitor SCH32615 on airway responses to rapid intravenous infusions of substance P (SP) and neurokinin A (NKA) and on recovery of administered tachykinins from arterial blood in anesthetized mechanically ventilated guinea pigs. SCH32615, in doses that cause a marked increase in the magnitude of bronchoconstriction induced by infused NKA, had little effect on the changes in pulmonary conductance (GL) or dynamic compliance induced by SP. In animals in which SCH32615 (1 mg/kg) was administered in combination with the angiotensin-converting enzyme (ACE) inhibitor captopril (5.7 mg/kg), the dose of SP required to decrease GL by 50% was fourfold less than in animals that received captopril alone (P < 0.005). SP measured in arterial blood withdrawn within 45 s of intravenous administration of this tachykinin was not different in control and SCH32615-treated animals, whereas captopril caused an approximately threefold increase in SP concentrations (P < 0.005). When SCH32615 and captopril were administered together, significantly more SP was recovered than when captopril or SCH32615 was administered alone (P < 0.0005). Our results are consistent with the hypothesis that both NEP and ACE contribute to the degradation of intravenously infused SP. ACE degradation of SP is sufficient to limit SP-induced bronchoconstriction even in the presence of specific NEP inhibition.

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.

PAMP is a novel inhibitor of the tachykinin release in the airway of guinea pigs

1997 ◽  
Vol 272 (6) ◽  
pp. L1066-L1069
Author(s):  
H. Kanazawa ◽  
H. Kamoi ◽  
T. Kawaguchi ◽  
S. Shoji ◽  
T. Fujii ◽  
...  
Keyword(s):  
Substance P ◽  
Bronchoalveolar Lavage ◽  
Guinea Pigs ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Neurokinin A ◽  
Dependent Manner ◽  
C Fiber ◽  
Dose Dependent

Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified hypotensive peptide, may play physiological roles in airway and cardiovascular controls. This study was designed to determine the mechanism responsible for the bronchoprotective effects of PAMP on capsaicin-induced bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M) significantly inhibited capsaicin-induced bronchoconstriction in a dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The concentration of immunoreactive substance P (SP) in bronchoalveolar lavage fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10 fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84 +/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for 10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction, whereas isoproterenol (10(-7) M) significantly inhibited exogenous tachykinin-induced bronchoconstriction. These findings suggest that the bronchoprotective effects of PAMP are mainly due to inhibition of the release of tachykinins at airway C-fiber endings.

Role of vagal afferents in the control of abdominal expiratory muscle activity in the dog

1991 ◽  
Vol 71 (5) ◽  
pp. 1795-1800 ◽  
Author(s):  
S. B. Hollstien ◽  
M. L. Carl ◽  
E. S. Schelegle ◽  
J. F. Green
Keyword(s):  
Muscle Activity ◽  
Vagal Afferents ◽  
Oblique Muscle ◽  
Vagus Nerves ◽  
Expiratory Muscle ◽  
C Fibers ◽  
C Fiber ◽  
Before And After ◽  
Afferent Vagal ◽  
Alpha Chloralose

We examined the contribution of afferent vagal A- and C-fibers on abdominal expiratory muscle activity (EMA). In seven spontaneously breathing supine dogs anesthetized with alpha-chloralose we recorded the electromyogram of the external oblique muscle at various vagal temperatures before and after the induction of a pneumothorax. When myelinated fibers were blocked selectively by cooling the vagus nerves to 7 degrees C, EMA decreased to 40% of control (EMA at 39 degrees C). With further cooling to 0 degrees C, removing afferent vagal C-fiber activity, EMA returned to 72% of control. On rewarming the vagus nerves to 39 degrees C, we then induced a pneumothorax (27 ml/kg) that eliminated the EMA in all the dogs studied. Cooling the vagus nerves to 7 degrees C, during the pneumothorax, produced a slight though not significant increase in EMA. However, further cooling of the vagus nerves to 0 degrees C caused the EMA to return vigorously to 116% of control. In three dogs, intravenous infusion of a constant incrementally increasing dose of capsaicin, a C-fiber stimulant, decreased EMA in proportion to the dose delivered. These results suggest that EMA is modulated by a balance between excitatory vagal A-fiber activity, most likely from slowly adapting pulmonary stretch receptors, and inhibitory C-fiber activity, most likely from lung C-fibers.

Ozone enhances excitabilities of pulmonary C fibers to chemical and mechanical stimuli in anesthetized rats

1998 ◽  
Vol 85 (4) ◽  
pp. 1509-1515 ◽  
Author(s):  
Ching-Yin Ho ◽  
Lu-Yuan Lee
Keyword(s):  
Low Dose ◽  
Acute Exposure ◽  
Right Atrial ◽  
Mechanical Stimuli ◽  
Lung Inflation ◽  
C Fibers ◽  
Arterial Blood ◽  
Baseline Activity ◽  
Tracheal Pressure ◽  
C Fiber

Acute exposure to ozone (O3) enhances pulmonary chemoreflex response to capsaicin, and an increased sensitivity of bronchopulmonary C-fiber afferent endings may be involved. The present study was aimed at determining the effect of O3 on the responses of pulmonary C fibers to chemical and mechanical stimuli. A total of 31 C fibers were studied in anesthetized, open-chest, and vagotomized rats. During control, right atrial injection of a low dose of capsaicin abruptly evoked a short and mild burst of discharge [0.77 ± 0.28 impulses (imp)/s, 2-s average]. After acute exposure to O3 (3 parts/million for 30 min), there was no significant change in arterial blood pressure, tracheal pressure, or baseline activity of C fibers. However, the stimulatory effect of the same dose of capsaicin on these fibers was markedly enhanced (6.05 ± 0.88 impulses/s; P < 0.01) and prolonged immediately after O3 exposure, and returned toward control in 54 ± 6 min. Similarly, the pulmonary C-fiber response to injection of a low dose of lactic acid was also elevated after O3 exposure. Furthermore, O3 exposure significantly potentiated the C-fiber response to constant-pressure (tracheal pressure = 30 cmH2O) lung inflation (control: 0.19 ± 0.07 imp/s; after O3: 1.12 ± 0.26 imp/s; P < 0.01). In summary, these results show that the excitabilities of pulmonary C-fiber afferents to lung inflation and injections of chemical stimulants are markedly potentiated after acute exposure to O3, suggesting a possible involvement of these afferents in the O3-induced changes in breathing pattern and chest discomfort in humans.

Enhanced lung C-fiber responsiveness in sensitized adult guinea pigs exposed to chronic tobacco smoke

2001 ◽  
Vol 91 (4) ◽  
pp. 1645-1654 ◽  
Author(s):  
Dale R. Bergren
Keyword(s):  
Tobacco Smoke ◽  
Guinea Pigs ◽  
Airway Responsiveness ◽  
Compressed Air ◽  
Sensory Receptor ◽  
Plasma Extravasation ◽  
C Fibers ◽  
C Fiber

Tobacco smoke (TS) exposure induces bronchoconstriction and increases airway secretions and plasma extravasation in certain sensitive individuals, particularly those with asthma. C-fiber activation also induces these effects. Although the mechanism by which chronic TS exposure induces airway dysfunction is not well understood, TS exposure may enhance C-fiber responsiveness. To investigate the effect of chronic TS exposure on C-fiber responsiveness to capsaicin and bradykinin, especially in atopic individuals, we exposed ovalbumin (OA)-sensitized guinea pigs to TS (5 mg/l air, 30 min/day for 7 days/wk) or to compressed air. Nonsensitized guinea pigs were also exposed to either compressed air or TS. Beginning after 120 days of exposure, C fibers and rapidly adapting receptors (RARs) were challenged with capsaicin and bradykinin. TS exposure enhanced sensory receptor and airway responsiveness to both intravenous capsaicin and bradykinin challenge. C-fiber, RAR, and airway responsiveness to capsaicin challenge was greatest in OA-sensitized guinea pigs exposed to TS. OA alone induced capsaicin hyperresponsiveness at 5 μg. Airway responsiveness to bradykinin was also greatest in OA-sensitized guinea pigs exposed to TS. OA alone enhanced C-fiber responsiveness to bradykinin at 5 and 10 μg. C-fiber activation by either agonist appeared direct, whereas RAR activation appeared indirect. Therefore, a mechanism of airway hyperirritability induced by the combination of OA sensitization and chronic TS exposure may include hyperirritability of lung C fibers.

Alveolar hypercapnia augments pulmonary C-fiber responses to chemical stimulants: role of hydrogen ion

2002 ◽  
Vol 93 (1) ◽  
pp. 181-188 ◽  
Author(s):  
Qihai Gu ◽  
Lu-Yuan Lee
Keyword(s):  
Hydrogen Ion ◽  
Right Atrial ◽  
Mechanical Stimuli ◽  
Hydrogen Ions ◽  
Lung Inflation ◽  
C Fibers ◽  
Arterial Blood ◽  
Blood Ph ◽  
C Fiber

To determine whether the excitabilities of pulmonary C fibers to chemical and mechanical stimuli are altered by CO2-induced acidosis, single-unit pulmonary C-fiber activity was recorded in anesthetized, open-chest rats. Transient alveolar hypercapnia (HPC) was induced by administering CO2-enriched gas mixture (15% CO2, balance air) via the respirator inlet for 30 s, which rapidly lowered the arterial blood pH from a baseline of 7.40 ± 0.01 to 7.17 ± 0.02. Alveolar HPC markedly increased the responses of these C-fiber afferents to several chemical stimulants. For example, the C-fiber response to right atrial injection of the same dose of capsaicin (0.25–1.0 μg/kg) was significantly increased from 3.07 ± 0.70 impulses/s at control to 8.48 ± 1.52 impulses/s during HPC ( n = 27; P < 0.05), and this enhanced response returned to control within ∼10 min after termination of HPC. Similarly, alveolar HPC also induced significant increases in the C-fiber responses to right atrial injections of phenylbiguanide (4–8 μg/kg) and adenosine (0.2 mg/kg). In contrast, HPC did not change the response of pulmonary C fibers to lung inflation. Furthermore, the peak response of these C fibers to capsaicin during HPC was greatly attenuated when the HPC-induced acidosis was buffered by infusion of bicarbonate (1.36–1.82 mmol · kg−1 · min−1 for 35 s). In conclusion, alveolar HPC augments the responses of these afferents to various chemical stimulants, and this potentiating effect of CO2 is mediated through the action of hydrogen ions on the C-fiber sensory terminals.

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