In Vivo Demonstration of Nonadrenergic Inhibitory Innervation of the Guinea Pig Trachea

Chesrown, Sarah E.; Venugopalan, C. S.; Gold, Warren M.; Drazen, Jeffrey M.

doi:10.1172/jci109674

Cited by 91 publications

(41 citation statements)

References 9 publications

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“…8). (Foster, 1964;Burden et al 1971;O'Donnell & Saar, 1973;Coburn & Tomita, 1973;Chesrown et al 1980;Yip et al 1981;Blackman & McCaig, 1983;Smith & Satchell, 1985). The present study demonstrates that the rostral portion of the guinea-pig trachealis receives its adrenergic innervation from postganglionic fibres that emanate from the superior cervical ganglia and merge with the rostral portion of the recurrent laryngeal nerves prior to innervating the trachea.…”

Section: Effect Of Capsaicin Desensitization On Vagally Mediated Relasupporting

confidence: 55%

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Relaxant innervation of the guinea‐pig trachealis: demonstration of capsaicin‐sensitive and ‐insensitive vagal pathways.

Canning

Undem

1993

The Journal of Physiology

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SUMMARY1. The guinea-pig trachea was isolated with its extrinsic innervation intact and placed in a water-jacketed dissecting dish containing warmed, oxygenated Krebs solution. The trachea was not separated from the oesophagus. Two adjacent cartilage rings of the rostral portion of the trachea were cut open opposite the trachealis and prepared for isometric tension measurements.2. Following the addition of atropine and contraction of the trachealis with prostaglandin F2a (PGF2.), stimulation of the cervical sympathetic trunks elicited relaxations that were abolished by propranolol or hexamethonium. Stimulation of the vagus nerves caudal to the nodose ganglia also elicited relaxations. These vagally mediated relaxations were unaffected by propranolol but were abolished by hexamethonium or by cutting the recurrent laryngeal nerves. 3. After cutting the vagi caudal to the nodose ganglia, stimulation of the vagi rostral to the nodose ganglia elicited relaxations of the trachealis that were not significantly affected by either propranolol or hexamethonium but were abolished by cutting the superior laryngeal nerves. Stimulation of right vagi which had undergone supranodose vagotomy 14 days prior to experimentation was without effect on the smooth muscle of the guinea-pig trachea while the response to stimulation of the left vagus was unchanged.4. Acute capsaicin desensitization abolished relaxations of the guinea-pig trachealis elicited by stimulation of the vagal fibres carried by the superior laryngeal nerves. In contrast, capsaicin desensitization only modestly inhibited relaxations elicited by stimulation of the preganglionic parasympathetic fibres carried by the recurrent laryngeal nerves and had no effect on sympathetic nerve-induced relaxations.5. Removing the oesophagus selectively abolished relaxations elicited by stimulation of both vagal pathways of non-adrenergic relaxant innervation. Nonadrenergic relaxations of the trachealis elicited by electrical field stimulation were unaffected by removing the oesophagus. Oesophagus removal also had no effect on the parasympathetic-cholinergic contractile innervation or the sympathetic relaxant innervation of the trachealis.* To whom correspondence should be addressed. MS 1153B. J. CANVING AND B. J. UTNDEM 6. The results indicate that the guinea-pig trachealis receives non-adrenergic relaxant innervation from both parasympathetic and capsaicin-sensitive vagal pathways. The results also suggest that the neurones mediating non-adrenergic relaxations of the trachea are sensitive to oesophagus removal. The observation that oesophagus removal abolishes parasympathetic relaxations of the trachealis while having no effect on parasympathetic contractions supports the hypothesis that the guinea-pig trachealis receives excitatory and inhibitory innervation from distinct vagal parasympathetic pathways.

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Section: Effect Of Capsaicin Desensitization On Vagally Mediated Relasupporting

confidence: 55%

“…The former can be elicited by stimulation of sympathetic nerves, whereas the non-adrenergic innervation is thought to arise from the vagus nerves (Burden, Parkes & Gardiner, 1971;Chesrown, Venugopalan, Gold & Drazen, 1980;Yip, Palombini & Coburn, 1981).…”

Section: Introductionmentioning

confidence: 99%

Relaxant innervation of the guinea‐pig trachealis: demonstration of capsaicin‐sensitive and ‐insensitive vagal pathways.

Canning

Undem

1993

The Journal of Physiology

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“…Guinea pig trachea possesses an inhibitory (bronchodilator) nonadrenergic, noncholinergic innervation associated with cholinergic nerves which may be partly mediated by NO (32,33). Although our data do not allow us to assess if there are airway sources ofendogenous NO in vivo, it clearly demonstrates that NO has the capacity to relax contracted airways in vivo.…”

Section: Discussionmentioning

confidence: 67%

Bronchodilator action of inhaled nitric oxide in guinea pigs.

Dupuy

Shore²,

Drazen³

et al. 1992

J. Clin. Invest.

304

129

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The effects of inhaling nitric oxide (NO) on airway mechanics were studied in anesthetized and mechanically ventilated guinea pigs. In animals without induced bronchoconstriction, breathing 300 ppm NO decreased baseline pulmonary resistance (RL) from 0.138±0.004 (mean±SE) to 0.125±0.002 cmH2O/ml s (P < 0.05). When an intravenous infusion of methacholine (3.5-12 ,ug/kg-min) was used to increase RL from 0.143±0.008 to 0.474±0.041 cmH2O/ml. s (P < 0.05), inhalation of 5-300 ppm NO-containing gas mixtures produced a dose-related, rapid, consistent, and reversible reduction of RL and an increase of dynamic lung compliance. The onset of bronchodilation was rapid, beginning within 30 s after commencing inhalation. An inhaled NO concentration of 15.0±2.1 ppm was required to reduce RL by 50% of the induced bronchoconstriction. Inhalation of 100 ppm NO for 1 h did not produce tolerance to its bronchodilator effect nor did it induce substantial methemoglobinemia (< 2%). The bronchodilating effects of NO were additive with the effects of inhaled terbutaline, irrespective of the sequence of NO and terbutaline administration. Inhaling aerosol generated from S-nitroso-N-acetylpenicillamine also induced a rapid and profound decrease of RL from 0.453±0.022 to 0.287±0.022 cmH2O/ml s, which lasted for over 15 min in guinea pigs bronchoconstricted with methacholine. Our results indicate that low levels ofinhaled gaseous NO, or an aerosolized NO-releasing compound are potent bronchodilators in guinea pigs. (J. Clin. Invest. 1992. 90:421428.)

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“…There is evidence, in vivo that sustained stimulation of the vagus nerve in the presence of atropine and propranolol can elicit an inhibitory response (by definition non-adrenergic, non-cholinergic) in a number of species including the guinea-pig (Chesrown et al, 1980;Diamond & O'Donnell, 1980;Irvin et al, 1980). Such a response was not seen in our isolated innervated tracheal preparations.…”

Section: Discussionmentioning

confidence: 68%

Studies on an isolated innervated preparation of guinea‐pig trachea

Blackman

McCaig

1983

British J Pharmacology

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1An isolated preparation of the guinea-pig trachea with intact parasympathetic and sympathetic innervation has been devised. Responses to nerve stimulation were recorded as increases or decreases in intraluminal pressure from the fluid-filled trachea. 2 The preparation maintained a positive resting intraluminal pressure of 3-4 cmH2O. This was unaffected by atropine, hexamethonium or propranolol. 3 Brief pressor responses, which could be completely blocked by atropine or hexamethonium, were obtained by applying short trains of stimuli to the cervical segment of the right vagus. The amplitude of responses was frequency-dependent up to a maximum at 40 Hz. 4 Depressor responses, more delayed and prolonged than the pressor responses and blocked by propranolol but not by hexamethonium, were obtained by stimulation of the right cervical sympathetic trunk or stellate ganglion in 70% of preparations. Dual pressor-depressor responses were observed in the remaining 30% of preparations. The pressor component was blocked by atropine, the depressor component by propranolol. 5 In the presence of atropine and propranolol, sustained sympathetic stimulation sometimes evoked a small, delayed pressor response which was blocked by phentolamine. 6 Under the same conditions, transmural stimulation produced a depressor response evidently due to non-adrenergic, non-cholinergic nerves. 7 Spontaneous activity was observed in some preparations under normal conditions, but could always be evoked by hypoxia. Responses to sympathetic stimulation were reduced both by hypoxia and during periods of spontaneous activity. 8 The principal advantage of this preparation is that it permits both excitatory and inhibitory responses to be elicited by stimulation of vagal and sympathetic nerves separately in the isolated trachea in the absence of agonist and antagonist drugs.

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In Vivo Demonstration of Nonadrenergic Inhibitory Innervation of the Guinea Pig Trachea

Cited by 91 publications

References 9 publications

Relaxant innervation of the guinea‐pig trachealis: demonstration of capsaicin‐sensitive and ‐insensitive vagal pathways.

Relaxant innervation of the guinea‐pig trachealis: demonstration of capsaicin‐sensitive and ‐insensitive vagal pathways.

Bronchodilator action of inhaled nitric oxide in guinea pigs.

Studies on an isolated innervated preparation of guinea‐pig trachea

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