Catecholamines abolish vagal but not acetylcholine tone in the intact cat trachea

To obtain evidence in the airways that catecholamines inhibit cholinergic neurotransmission, we recorded transverse tension in the posterior wall of an upper tracheal segment in anesthetized cats and compared the inhibitory effect of stimulating cervical sympathetic nerves when segment contraction was evoked by endogenous acetylcholine (vagal tone) with the effect when contraction was evoked by exogenous acetylcholine applied directly to the mucosal surface of the tracheal segment (ACh tone). We found that sympathetic stimulation abolished all contraction evoked by vagal tone but reduced ACh tone by only one-half. In a second group of cats we compared the inhibitory effects of sympathetic stimulation and intravenous isoproterenol during vagal and ACh tone and also during tone evoked by exogenous 5-hydroxytryptamine (5-HT tone). Sympathetic stimulation or isoproterenol injection abolished all vagal and 5-HT tone but again reduced ACh tone by only one-half. Our results suggest that catecholamines released from sympathetic nerves or injected into the circulation completely inhibit vagal tone. This inhibition may be partially responsible for inducing relaxation in airway smooth muscle.     

Neural control of relaxation in cat airways smooth muscle

Functional innervation of cat airways smooth muscle was examined in isolated segments of trachea and bronchi using electrical field stimulation (EFS) techniques. Field stimulation caused contraction in tissues at resting tone and biphasic responses (contraction followed by relaxation) in tissues precontracted with 5-hydroxytryptamine (5-HT). Contractions were abolished by 10(-6) M atropine. Inhibitory responses were dependent on impulse voltage, duration, and frequency. At low voltages (less than or equal to 10 V) and pulse durations (less than or equal to 0.3 ms), EFS induced relaxations were abolished by 3 X 10(-6) M tetrodotoxin (TTX). Greater stimulus parameters elicited TTX-resistant relaxations. Pretreatment of the tissues with 10(-6) M propranolol and 10(-5) M guanethidine caused rightward shifts in relaxation frequency-response curves. These findings indicate that cat airways are innervated by excitatory cholinergic, inhibitory adrenergic, and inhibitory nonadrenergic noncholinergic (NANC) nerves. Pretreatment of the tissues with hexamethonium, cimetidine, indomethacin, or nordihydroguaiaretic acid did not affect NANC relaxation responses. It is concluded that NANC inhibitory responses in cat airway smooth muscle are mediated through intrinsic postganglionic nerve fibers and occur independently of histamine H2-receptor activation and without involvement of cyclooxygenase or lipoxygenase products of arachidonic acid metabolism.     

Influence of ventrolateral surface of medulla on reflex tracheal constriction

To assess the role of structures located superficially near the ventrolateral surface of the medulla on the reflex constriction of tracheal smooth muscle that occurs when airway and pulmonary receptors are stimulated mechanically or chemically, experiments were conducted in alpha-chloralose-anesthetized, paralyzed, and artificially ventilated cats. Pressure changes within a bypassed segment of the trachea were used as an index of alterations smooth muscle tone. The effects of focal cooling of the intermediate areas or topically applied lidocaine on the ventral surface of the medulla on the response of the trachea to mechanical and chemical stimulation of airway receptors were examined. Atropine abolished tracheal constriction induced by mechanical stimulation of the carina or aerosolized histamine, showing that the responses were mediated over vagal pathways. Moderate cooling of the intermediate area (20 degrees C) or local application of lidocaine significantly decreased the tracheal constrictive response to mechanical activation of airway receptors. Furthermore, when the trachea was constricted by histamine, cooling of the intermediate area significantly diminished the increased tracheal tone, whereas rewarming restored tracheal tone to the previous level. These findings suggest that under the conditions of the experiments the ventral surface of the medulla plays an important role in constriction of the trachea by inputs from intrapulmonary receptors and in the modulation of parasympathetic outflow to airway smooth muscle.     

Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons.

In ferrets, we investigated the presence of choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), and markers for nitric oxide synthase (NOS) in preganglionic parasympathetic neurons innervating extrathoracic trachea and intrapulmonary airways. Cholera toxin beta-subunit, a retrograde axonal transganglionic tracer, was used to identify airway-related vagal preganglionic neurons. Double-labeling immunohistochemistry and confocal microscopy were employed to characterize the chemical nature of identified airway-related vagal preganglionic neurons at a single cell level. Physiological experiments were performed to determine whether activation of the VIP and ChAT coexpressing vagal preganglionic neurons plays a role in relaxation of precontracted airway smooth muscle tone after muscarinic receptor blockade. The results showed that 1) all identified vagal preganglionic neurons innervating extrathoracic and intrapulmonary airways are acetylcholine-producing cells, 2) cholinergic neurons innervating the airways coexpress ChAT and VIP but do not contain NOS, and 3) chemical stimulation of the rostral nucleus ambiguus had no significant effect on precontracted airway smooth muscle tone after muscarinic receptor blockade. These studies indicate that vagal preganglionic neurons are cholinergic in nature and coexpress VIP but do not contain NOS; their stimulation increases cholinergic outflow, without activation of inhibitory nonadrenergic, noncholinergic ganglionic neurons, stimulation of which induces airway smooth muscle relaxation. Furthermore, these studies do not support the possibility of direct inhibitory innervation of airway smooth muscle by vagal preganglionic fibers that contain VIP.     

Interaction between histamine and vagal stimulation on tracheal smooth muscle in dogs

We examined the interaction between histamine and vagal efferent activity on airway smooth muscle reactivity in 11 anesthetized vagotomized dogs using an isolated closed segment of the intrathoracic trachea filled with Tyrode solution under an isovolumetric condition. Intratracheal pressure change was measured as an index of tracheal smooth muscle tone. The administration into the tracheal segment of histamine (0.1 or 1.0 mg/ml) in six dogs and methacholine chloride (0.001 or 0.01 mg/ml) in the other five dogs elevated intratracheal pressure by about 5 cmH2O. The electrical stimulation of the peripheral ends of both of the cut cervical vagus nerves in the presence of histamine produced significantly greater responses than the additive responses of these two stimuli applied individually (two-way analysis of variance, P less than 0.025). However, the combined effects of vagal stimulation and methacholine were not significantly different from the additive responses of these two stimuli applied individually. The average values of intratracheal pressure elevated by the combined effects of vagal stimulation and histamine were significantly higher than those obtained by the combination of vagal stimulation and methacholine (two-way analysis of variance, P less than 0.01). This suggests that histamine potentiates tracheal smooth muscle reactivity to electrical vagal stimulation, which may contribute to the hyperreactivity observed in patients with asthma.     

Functional anatomy of the vagal innervation of the cervical trachea of the dog.

The canine cervical trachea has been used for numerous studies regarding the neural control of tracheal smooth muscle. The purpose of the present study was to determine whether there is lateral dominance by either the left or right vagal innervation of the canine cervical trachea. In anesthetized dogs, pressure in the cuff of the endotracheal tube was used as an index of smooth muscle tone in the trachea. After establishment of tracheal tone, as indicated by increased cuff pressure, either the right or left vagus nerve was sectioned followed by section of the contralateral vagus. Sectioning the right vagus first resulted in total loss of tone in the cervical trachea, whereas sectioning the left vagus first produced either a partial or no decrease in tracheal tone. After bilateral section of the vagi, cuff pressure was recorded during electrical stimulation of the rostral end of the right or left vagus. At the maximum current strength used, stimulation of the left vagus produced tracheal constriction that averaged 28.5% of the response to stimulation of the right vagus (9.0 +/- 1.8 and 31.6 +/- 2.5 mmHg, respectively). In conclusion, the musculature of cervical trachea in the dog appears to be predominantly controlled by vagal efferents in the right vagus nerve.     

Reflex tracheal contraction evoked in dogs by bronchodilator prostaglandins E2 and I2

Bronchodilator prostaglandins E2 and I2 may cause airway irritation and bronchoconstriction in human subjects. These experiments were designed to test the hypothesis that this paradoxical bronchoconstriction is a vagal reflex triggered by stimulation of airway afferents. We recorded smooth muscle tension in an innervated upper tracheal segment in anesthetized dogs and injected prostaglandins into the general circulation or into a bronchial artery or administered them as aerosol to the lungs. Prostaglandins usually caused tracheal contraction, which survived vagal cooling to 5-7 degrees C but was abolished at 0 degrees C. Vagally mediated tracheal contraction was also evoked when prostacyclin was injected into the pulmonary circulation of dogs whose pulmonary and systemic circulations were independently pump perfused. Recordings of afferent vagal impulses indicated that bronchial arterial injection of prostaglandins stimulated bronchial C-fibers; aerosols of prostaglandin stimulated pulmonary and bronchial C-fibers and C-fibers in extrapulmonary airways. We postulate that in susceptible human subjects concentrations of these prostaglandins too low to have direct bronchodilator effects may cause reflex bronchoconstriction by stimulating afferent vagal C-fibers in the lower airways.     

Augmentation of parasympathetic contraction in tracheal and bronchial airways by PGF2 alpha in situ

We studied the effect of exogenous prostaglandin F2 alpha (PGF2 alpha) on airway smooth muscle contraction caused by parasympathetic stimulation in 22 mongrel dogs in situ. Voltage (0-30 V, constant 20 Hz) and frequency-response (0-25 Hz, 25 V) curves were generated by stimulating the cut ends of both cervical vagus nerves. Airway response was measured isometrically as active tension (AT) in a segment of cervical trachea and as change in airway resistance (RL) and dynamic compliance (Cdyn) in bronchial airways. One hour after 5 mg/kg iv indomethacin, a cumulative frequency-response curve was generated in nine animals by electrical stimulation of the vagus nerves at 15-s intervals. Reproducibility was demonstrated by generating a second curve 7 min later. A third frequency-response curve was generated during active contraction of the airway caused by continuous intravenous infusion of 10 micrograms X kg-1 X min-1PPGF2 alpha. Additional frequency-response studies were generated 15 and 30 min after PGF2 alpha, when airway contractile response (delta RL = +2.8 +/- 0.65 cmH2O X 1(-1) X s; delta Cdyn = -0.0259 +/- 0.007 1/cmH2O) returned to base line. Substantial augmentation of AT, RL, and Cdyn responses was demonstrated in every animal studied (P less than 0.01 for all points greater than 8 Hz) 15 min after PGF2 alpha. At 30 min, response did not differ from initial base-line control. In four animals receiving sham infusion, all frequency-response curves were identical. We demonstrate that PGF2 alpha augments the response to vagus nerve stimulation in tracheal and bronchial airways. Augmentation does not depend on PGF2 alpha-induced active tone.     

Maturation of respiratory reflex responses in the piglet

Stimulation of chemo-, irritant, and pulmonary C-fiber receptors reflexly constricts airway smooth muscle and alters ventilation in mature animals. These reflex responses of airway smooth muscle have, however, not been clearly characterized during early development. In this study we compared the maturation of reflex pathways regulating airway smooth muscle tone and ventilation in anesthetized, paralyzed, and artificially ventilated 2- to 3- and 10-wk-old piglets. Tracheal smooth muscle tension was measured from an open tracheal segment by use of a force transducer, and phrenic nerve activity was measured from a proximal cut end of the phrenic nerve. Inhalation of 7% CO2 caused a transient increase in tracheal tension in both age groups, whereas hypoxia caused no airway smooth muscle response in either group. The phrenic responses to 7% CO2 and 12% O2 were comparable in both age groups. Lung deflation and capsaicin (20 micrograms/kg iv) administration did not alter tracheal tension in the younger piglets but caused tracheal tension to increase by 87 +/- 28 and 31 +/- 10%, respectively, in the older animals (both P less than 0.05). In contrast, phrenic response to both stimuli was comparable between ages: deflation increased phrenic activity while capsaicin induced neural apnea. Laryngeal stimulation did not increase tracheal tension but induced neural apnea in both age groups. These data demonstrate that between 2 and 10 wk of life, piglets exhibit developmental changes in the reflex responses of airway smooth muscle situated in the larger airways in response to irritant and C-fiber but not chemoreceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of neutrophil depletion and repletion on PAF-induced hyperresponsiveness of canine trachea.

Platelet-activating factor (PAF) has been implicated as a mediator of airway hyperresponsiveness. PAF, infused intra-arterially into the canine cervical trachea, causes adherence of neutrophils to vascular endothelium, increases vascular permeability, and increases the responsiveness of tracheal muscle to parasympathetic stimulation. We hypothesized that the increase in airway responsiveness induced by PAF in this model depends on the presence of neutrophils. To test this hypothesis, we perfused a cervical tracheal segment with autologous blood depleted of leukocytes or with similar leukocyte-depleted blood that had been repleted with its neutrophils. Fifteen minutes after the onset of perfusion with either leukocyte-depleted or neutrophil-repleted blood, PAF infusion was begun into the tracheal arterial vasculature. The contractile response of the tracheal muscle to parasympathetic stimulation was measured before and 15 and 30 min after the onset of PAF infusion. PAF did not significantly change the response of tracheal muscle during perfusion with neutrophil-depleted blood but increased the response of tracheal muscle during perfusion with neutrophil-repleted blood. We conclude that the increase in canine tracheal muscle response induced by intra-arterial PAF depends on neutrophils.     

Release of prostaglandin-like material from isolated cat tracheal muscle by electrical and mechanical stimulation.

Release of PGE-like material has been studied on the isolated continuously-superfused cat tracheal muscle using dynamic bioassay methods. The effluent of transmural electrically-stimulated cat tracheal muscle induced a contraction when superfused over the rat stomach fundus strip. This response did not alter with atropine, methysergide, phentolamine and propranolol but was inhibited by aspirin and Sc 19220. The same myotropic activity in the effluent was found when trachea was mechanically stimulated by an additional increase in tension. The effluent from mechanically- and electrically-stimulated tracheal muscle caused a definite relaxation when superfused over a second cat tracheal muscle contracted by serotonin and pretreated with propranolol. Electrically-stimulated cat trachea itself gave a relaxant response which was blocked by propranolol but potentiated by aspirin. From these results it was concluded that both electrical and mechanical stimulation can elicit a release of PGE-like material from isolated cat tracheal muscle.     

Nicotine-induced respiratory effects of cigarette smoke in dogs

We report that nicotine is responsible for both a blood-borne stimulation of the respiratory center and a direct effect on intrathoracic airway tone in dogs. We introduced cigarette smoke into the lungs of donor dogs and injected arterial blood obtained from them into the circulation of recipient dogs to show that a blood-borne material increased breathing and airway smooth muscle tone. Smoke from cigarettes containing 2.64 mg of nicotine was effective; that from cigarettes containing 0.42 mg of nicotine was not. Nicotine, in doses comparable to the amounts absorbed from smoke, also increased breathing and tracheal smooth muscle tension when injected into the vertebral circulation of recipient dogs. Finally, blockade of nicotine receptors in the central nervous system and in the airway parasympathetic ganglia inhibited the effects of inhaled cigarette smoke and intravenous nicotine on the respiratory center and on bronchomotor tone. We conclude that nicotine absorbed from cigarette smoke is the main cause of cigarette smoke-induced bronchoconstriction. It caused central respiratory stimulation, resulting in increased breathing and airway smooth muscle tension, and had a direct effect on airway parasympathetic ganglia as well.     

Stimulation of splanchnic afferents reflexly relaxes tracheal smooth muscle in dogs

Although chemical stimulation of abdominal visceral afferents has been shown to reflexly increase cardiovascular and ventilatory function, the effect of stimulating these afferents on airway smooth muscle is unknown. Therefore, we recorded transverse smooth muscle tension from an innervated segment of trachea in chloralose-anesthetized dogs while we topically applied capsaicin (200 micrograms/ml) and bradykinin (0.01-10 micrograms/ml) to the serosal surfaces of the stomach, small intestine, and gallbladder. Application of these irritant substances to the stomach and small intestine decreased tracheal tension and increased mean arterial pressure. However, application of capsaicin and bradykinin to the gallbladder had only small effects on both of these variables. Cutting the splanchnic nerves abolished or greatly attenuated the decreases in tension and increases in mean arterial pressure, whereas cutting the vagi had no effect on them. We conclude that stimulation of splanchnic afferent endings in the stomach and small intestine reflexly relaxes tracheal smooth muscle in dogs. This effect may be one component of the constellation of autonomic responses reflexly evoked by abdominal visceral pain and inflammation.     

Stimulation frequency-dependent nonadrenergic noncholinergic airway responses of the guinea pig

We examined the inhibitory and excitatory components of the nonadrenergic noncholinergic (NANC) innervation of the guinea pig airways by in vivo and in vitro methods. Electrical stimulation of the vagus in chloralose-urethan-anesthetized guinea pigs after cholinergic and adrenergic blockade produced peripheral airway constriction (insufflation pressure) and tracheal relaxation (pouch pressure). Vagal stimulation was applied for 90 s at 5-V pulses of 2-ms duration at frequencies of 5, 15, 25, and 35 Hz in each group (n = 6). The pouch relaxation peaked at 15 Hz. The insufflation pressure was highest at 5 Hz. Field stimulations of the same frequencies were applied on tracheal spirals and lung parenchymal strips. The maximal relaxation of the trachea occurred at 15-35 Hz. The lung parenchymal strip tensions increased almost linearly as the frequency increased from 5 to 35 Hz. The results of the study indicated a frequency-dependent response for both excitatory and inhibitory components of the NANC, which operate at different frequencies for optimal responses.     

Reflex regulation of airway smooth muscle tone.

Autonomic nerves in most mammalian species mediate both contractions and relaxations of airway smooth muscle. Cholinergic-parasympathetic nerves mediate contractions, whereas adrenergic-sympathetic and/or noncholinergic parasympathetic nerves mediate relaxations. Sympathetic-adrenergic innervation of human airway smooth muscle is sparse or nonexistent based on histological analyses and plays little or no role in regulating airway caliber. Rather, in humans and in many other species, postganglionic noncholinergic parasympathetic nerves provide the only relaxant innervation of airway smooth muscle. These noncholinergic nerves are anatomically and physiologically distinct from the postganglionic cholinergic parasympathetic nerves and differentially regulated by reflexes. Although bronchopulmonary vagal afferent nerves provide the primary afferent input regulating airway autonomic nerve activity, extrapulmonary afferent nerves, both vagal and nonvagal, can also reflexively regulate autonomic tone in airway smooth muscle. Reflexes result in either an enhanced activity in one or more of the autonomic efferent pathways, or a withdrawal of baseline cholinergic tone. These parallel excitatory and inhibitory afferent and efferent pathways add complexity to autonomic control of airway caliber. Dysfunction or dysregulation of these afferent and efferent nerves likely contributes to the pathogenesis of obstructive airways diseases and may account for the pulmonary symptoms associated with extrapulmonary disorders, including gastroesophageal reflux disease, cardiovascular disease, and rhinosinusitis.     

Methacholine causes reflex bronchoconstriction

To determine whether methacholine causes vagally mediated reflexconstriction of airway smooth muscle, we administered methacholine tosheep either via the bronchial artery or as an aerosol via tracheostomyinto the lower airways. We then measured the contraction of anisolated, in situ segment of trachealis smooth muscle and determinedthe effect of vagotomy on the trachealis response. Administeringmethacholine to the subcarinal airways via the bronchial artery(0.5-10.0 µg/ml) caused dose-dependent bronchoconstriction andcontraction of the tracheal segment. At the highest methacholine concentration delivered, trachealis smooth muscle tension increased anaverage of 186% over baseline. Aerosolized methacholine (5-7 breaths of 100 mg/ml) increased trachealis tension by 58% and airwaysresistance by 183%. As the bronchial circulation in the sheep does notsupply the trachea, we postulated that the trachealis contraction wascaused by a reflex response to methacholine in the lower airways.Bilateral vagotomy essentially eliminated the trachealis response andthe airways resistance change after lower airways challenge (either viathe bronchial artery or via aerosol) with methacholine. We concludethat 1) methacholine causes asubstantial reflex contraction of airway smooth muscle and2) the assumption may not be validthat a response to methacholine in humans or experimental animalsrepresents solely the direct effect on smooth muscle.

     

Neuropeptides in guinea pig trachea: Distribution and evidence for the release of CGRP into tracheal lumen

The airways of the guinea pig are richly innervated by peptide-containing nerve fibers. Among the most abundant neuropeptides are calcitonin gene-related peptide (CGRP) and substance P (SP), which are stored in nerve fibers located predominantly within and beneath the epithelium, and vasoactive intestinal peptide (VIP), which is located in fibers running mainly among smooth muscle bundles and seromucous glands. Sensory denervation (capsaicin treatment) of adult guinea pigs caused an almost total disappearance of CGRP- and SP-containing nerve fibers, while the density of VIP-containing nerve fibers located in smooth muscle seemed to increase. In the isolated trachea, perfused luminally, CGRP was found to appear in the intraluminal fluid after exposure to capsaicin but not after electrical vagal stimulation. CGRP concentrations in the tracheal wall did not change significantly. Luminally applied CGRP did not affect smooth muscle tension, measured as intraluminal volume changes.     

Serotonergic modulation of murine fundic tone

Fundic tone is maintained through a balance of excitatory and inhibitory input to fundic smooth muscle. The aim of this study was to determine the role of serotonin (5-HT) and 5-HT receptors in modulating murine fundic tone. Muscle strips were prepared from the murine fundus. Intracellular recordings were made from circular smooth muscle cells, and the effects of 5-HT on tone and excitatory and inhibitory junction potentials evoked by electrical field stimulation (EFS) were determined. 5-HT induced a concentration-dependent contraction and smooth muscle depolarization that was tetrodotoxin resistant. The 5-HT(1B/D) receptor antagonists GR-127935 and BRL-155172 significantly inhibited 5-HT-induced contractions. The 5-HT(1B/D) agonist sumatriptan contracted murine fundic muscle. The 5-HT(1A) receptor agonist buspirone relaxed fundic smooth muscle, and the relaxation was inhibited by WAY-100135 but not by N(omega)-nitro-l-arginine or tetrodotoxin. 5-HT enhanced both the excitatory and inhibitory responses to EFS. The 5-HT(3) receptor antagonist MDL-72222 partly inhibited both the excitatory and inhibitory response elicited by EFS, whereas the 5-HT(4) receptor antagonist GR-113808 partly inhibited the EFS-evoked inhibitory response. The 5-HT reuptake inhibitor fluoxetine contracted smooth muscle strips, a contraction that was partially inhibited by GR-127935 and abolished by tetrodotoxin. In conclusion, the data suggest that 5-HT modulates murine fundic contractile activity through several different receptor subtypes. Sustained release of 5-HT maintains fundic tone through postjunctional 5-HT(1B/D) receptors. 5-HT(3) receptors modulate excitatory neural input to murine fundic smooth muscle, and both 5-HT(3) and 5-HT(4) receptors modulate inhibitory neural input to murine fundic smooth muscle.     

Inhibitory innervation to the guinea pig trachealis muscle

The inhibitory innervation of the cervical trachea was studied in situ in anesthetized male guinea pigs. We measured effects of electrical stimulation of vagal motor and sympathetic trunk nerve fibers, during atropine, on trachealis muscle tension. Effects of direct transmural stimulation of trachealis muscle were also determined. We confirmed the dual nature of the inhibitory innervation to this muscle. Vagal motor inhibitory nerves are shown to be preganglionic. Neural transmission at the level of the ganglia is characterized by filtering of high frequency action potentials. The neurotransmitter at the myoneural junction is unidentified but is not norepinephrine. Maximal relaxation accounts for about 20-40% of maximal relaxations seen with transmural stimulation of trachealis muscle in the presence of atropine. Sympathetic trunk nerve fibers are also preganglionic. Neurotransmission at the level of the ganglia is apparently 1:1 at high-action potential frequencies. Norepinephrine released presynaptically has access to smooth muscle beta- but not alpha-receptors. Maximal adrenergic relaxations account for 60-80% of total transmural stimulation relaxations. Transmural stimulation relaxations appear to be accounted for by release of neurotransmitter from sympathetic adrenergic plus vagal nonadrenergic postganglionic nerve fibers.     

In vivo recording of electrical activity of canine tracheal smooth muscle.

Electrical activity of the tracheal smooth muscle was studied using extracellular bipolar electrodes in 37 decerebrate, paralyzed, and mechanically ventilated dogs. A spontaneous oscillatory potential that consisted of a slow sinusoidal wave of 0.57 +/- 0.13 (SD) Hz mean frequency but lacked a fast spike component was recorded from 15 dogs. Lung collapse accomplished by bilateral pneumothoraxes evoked or augmented the slow potentials that were associated with an increase in tracheal muscle contraction in 26 dogs. This suggests that the inputs from the airway mechanoreceptors reflexly activate the tracheal smooth muscle cells. Bilateral vagal transection abolished both the spontaneous and the reflexly evoked slow waves and provided relaxation of the tracheal smooth muscle. Electrical stimulation of the distal nerve with a train pulse (0.5 ms, 1-30 Hz) evoked slow-wave oscillatory potentials accompanied by a contraction of the tracheal smooth muscle in all the experimental animals. Our observations in this in vivo study confirm that the electrical activity of tracheal smooth muscle consists of slow oscillatory potentials and that tracheal contraction is at least partly coupled to the slow-wave activity of the smooth muscle.