Reflex regulation of airway sympathetic nerves in guinea-pigs (original) (raw)
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British Journal of Pharmacology, 1990
In the present study we have examined whether neuropeptide Y (NPY) interferes with non-adrenergic, non-cholinergic nerve-mediated contractions and relaxations in the guinea-pig airways. In these experiments we have used ring preparations of bronchi and trachea, incubated in the presence of atropine, propranolol and indomethacin (each 1 yM). 2 The contractile response to electrical stimulation of non-adrenergic, non-cholinergic nerve fibres was suppressed by NPY and NPY 13-36 in a concentration-dependent manner, these agents having similar inhibitory potencies. NPY caused a more complete inhibition than the C-terminal fragment. 3 NPY affected neither the basal tension nor the substance P-evoked contraction in the bronchi and trachea and did not interfere with nerve-mediated, non-adrenergic relaxation in the trachea. 4 On the basis of these results, it is suggested that NPY may act on the terminals of sensory neurones in the airways to prevent antidromic, excitatory neurotransmission by inhibiting transmitter release.
British Journal of Pharmacology, 1992
We examined whether the non-adrenergic, non-cholinergic (NANC) neural response can counteract changes in smooth-muscle tone with and without simultaneous sympathetic activation in guinea-pig airways. 2 Isolated airway preparations were pretreated with indomethacin (1OjM) and incubated with either atropine (1 AM) and guanethidine (10 jLM) or atropine (1 pM) alone. The response to electrical field stimulation (EFS: 1200 mA, 0.5 ms, 3 Hz for 240 s) was studied at various levels of tone prior to EFS: first without induced tone, then at a moderate tone induced by histamine (0.3 AM) and finally at a high tone induced by histamine (6 JAM). 3 The response to EFS was a contraction when the tone prior to EFS was low and a relaxation when the tone prior to EFS was high. These responses converged towards a similar level of tone, in the distal trachea and in the main bronchus, with and without guanethidine. 4 The mean (s.e.mean) level of tone towards which the responses to EFS converged was lower after incubation with atropine alone compared with incubation with atropine and guanethidine, both in the distal trachea [8 (1)% compared with 30 (6)% of maximum tone] and in the main bronchus [28 (4)% compared with 57 (2)% of maximum tone]. In separate experiments, the guanethidine-induced effect on the responses to EFS was imitated by propranolol (I JAM) but not by prazosin (0.3 JIM) and yohimbine (1 AM). 5 These findings indicate that the NANC neural response can counteract changes in airway smoothmuscle tone via a contraction or via a relaxation, depending on the tone prior to activation. This stabilizing effect on tone does not appear to depend upon adrenergic activation per se. The level of tone towards which the NANC responses converge can, however, be reduced by P-adrenoceptor activation, thus suggesting an interaction which provides protection from severe airway smooth-muscle contraction. Keywords: Guinea-pig; airway tone; in vitro; neural regulation; non-adrenergic, non-cholinergic neural responses; smoothmuscle tone; sympathetic ' Author for correspondence. In the present study, we examined the ability of contractile and relaxant NANC responses to counteract changes in smooth-muscle tone prior to NANC activation, with and without simultaneous sympathetic activation, in guinea-pig isolated airways. We also characterized the interaction between NANC and sympathetic responses. Methods Airway preparation Twenty-eight female Dunkin-Hartley guinea pigs (300-500 g) were killed by cervical dislocation and exsanguination. The thoracic contents were removed and placed in a 200 ml dissection bath filled with oxygenated (94% 02:6% CO2) Krebs-Ringer solution (mM: NaCl 118, KCI 5.9, CaC12 2.5, MgSO4 1.2, NaH2PO4 1.2, NaHCO3 25.5 and glucose 5.6) at room temperature. The intermediate (cervical) trachea, the distal (intrathoracic) trachea and the main bronchi were dissected free and two airway rings were cut transversely from each airway segment, each ring containing four to five cartilaginous rings. The airway rings were opened longitudinally along the anterior, cartilaginous part and connected to steel hooks as isolated strips. These preparations were mounted vertically in warmed (37C) and oxygenated 8 ml organ baths, which were continuously flushed with fresh Krebs-Ringer solution (0.4 ml min'). The histological evalu-'." Macmillan Press Ltd, 1992
Innervation of lower airways and neuropeptide effects on bronchial and vascular tone in the pig
Cell and Tissue Research, 1990
The occurrence and distribution of peptidecontaining nerve fibres [substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), neuropeptide Y (NPY)] and noradrenergic nerve fibres [tyrosine hydroxylase (TH)-and dopamine beta hydroxylase (DBH)-positive] in the airways of the pig were studied by means of immunohistochemistry. SP-and CGRPimmunoreactive (-IR) nerve fibres were present close to and within the lining respiratory epithelium, around blood vessels, within the tracheobronchial smooth muscle layer and around local tracheobronchial ganglion cells. The content of CGRP-and neurokinin A (NKA)like immunoreactivity (-LI) measured by radioimmunoassay (RIA) was twice as high in the trachea compared to that in the peripheral bronchi. SP was a more potent constrictor agent than NKA on pig bronchi in vitro. CGRP had a relaxant effect on precontracted pig bronchi. On blood vessels CGRP exerted a relaxant effect that was more pronounced on pulmonary arteries than on bronchial arteries. VIP/PHI-IR fibres were seen in association with exocrine glands and in the tracheobronchial smooth muscle layer. VIP-positive nerve fibres were abundant around blood vessels in the trachea but sparse or absent around blood vessels in the peripheral bronchi. This histological finding was supported by RIA; it was shown that the content of peptides displaying VIP-like immunoreactivity (-LI) was 18 times higher in the trachea compared to peripheral bronchi. VIP was equally potent as CGRP in relaxing precontracted pig bronchi in vitro. Both bronchial and pulmonary arteries were relaxed by VIP. NPY was colocalized with VIP in tracheal periglandular nerve fibres and in nerve fibres within the tracheobronchial smooth muscle layer. NPY was also present in noradrenergic (DBH-positive) vascular nerve fibres. The content of NPY was much higher (15-fold) in the trachea compared to small bronchi. NPY caused a contraction of both pulmonary and bronchial Send offprint requests to: Dr. Claes-Roland Martling, Department of Anaesthesia, Karolinska Hospital, Box 60500, S-10401 Stockholm, Sweden arteries. The bronchial smooth muscle contraction to field stimulation in vitro was purely cholinergic. A noncholinergic relaxatory effect following field stimulation was observed after bronchial precontraction. Capsaicin had no effect on pig bronchi in vitro.
Physiological Reports, 2018
The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1-sensitive pulmonary spinal sensory fibers by agonist application to the visceral pleura of the lung and by administration into the primary bronchus in anesthetized, bilaterally vagotomized, adult Sprague-Dawley rats. Application of bradykinin (BK) to the visceral pleura of the lung produced an increase in mean arterial pressure (MAP), heart rate (HR), and RSNA. This response was significantly greater when BK was applied to the ventral surface of the left lung compared to the dorsal surface. Conversely, topical application of capsaicin (Cap) onto the visceral pleura of the lung, produced a biphasic reflex change in MAP, coupled with increases in HR and RSNA which was very similar to the hemodynamic response to epicardial application of Cap. This reflex was also evoked in animals with intact pulmonary vagal innervation and when BK was applied to the distal airways of the lung via the left primary bronchus. In order to further confirm the origin of this reflex, epidural application of a selective afferent neurotoxin (resiniferatoxin, RTX) was used to chronically ablate thoracic TRPV1-expressing afferent soma at the level of T1-T4 dorsal root ganglia pleura. This treatment abolished all sympatho-excitatory responses to both cardiac and pulmonary application of BK and Cap in vagotomized rats 9-10 weeks post-RTX. These data suggest the presence of an excitatory pulmonary chemosensitive sympathetic afferent reflex. This finding may have important clinical implications in pulmonary conditions inducing sensory nerve activation such as pulmonary inflammation and inhalation of chemical stimuli.
Nonadrenergic, noncholinergic airway inhibitory nerves
The European Respiratory Journal, 1992
Nonadrenergic, noncholinerglc (NANC) nerves, whlc:b cause relaxa· tion of airway smooth muscle, have been described In several species Including man. Stimulation of efferent vagus nerves during cholinergic and adrenergic blockade Induces a pronounced bronchodllatlon In the cat. In more recent stud· les In man, capsaicin Inhalation or mechanical Irritation of the larynx, under conditions of cholinergic and adrenergic blockade, have been shown to cause a transient bronchodilator response.
Journal of Applied Physiology, 2015
Acute inhalation of airborne pollutants alters cardiovascular function and evidence suggests that pollutant-induced activation of airway sensory nerves via the gating of ion channels is critical to these systemic responses. Here, we have investigated the effect of capsaicin [transient receptor potential (TRP) vanilloid 1 (TRPV1) agonist], AITC [TRP ankyrin 1 (TRPA1) agonist], and ATP (P2X2/3 agonist) on bronchopulmonary sensory activity and cardiovascular responses of conscious Sprague-Dawley (SD) rats. Single fiber recordings show that allyl isothiocyanate (AITC) and capsaicin selectively activate C fibers, whereas subpopulations of both A and C fibers are activated by stimulation of P2X2/3 receptors. Inhalation of the agonists by conscious rats caused significant bradycardia, atrioventricular (AV) block, and prolonged PR intervals, although ATP-induced responses were lesser than those evoked by AITC or capsaicin. Responses to AITC were inhibited by the TRP channel blocker rutheniu...
Reflex ventilatory effects of KCl stimulation of lung receptors with sympathetic afferents
Respiration Physiology, 1990
The purpose of this study was to determine the reflex ventilatory effects produced by lung receptors with sympathetic afferent nerves. Seven dogs were anesthetized with sodium pentobarbital, placed on a ventilator, and vagotomized. The chest was opened through a mid-sternal incision. Diaphragm EMG (D-EMG), right and left triangularis sterni EMG (TS-EMG), systemic arterial blood pressure (BP), and tracheal presst, re were recorded before and after the application of 2 M KCI to the right or left lung near the venous hilum. The reflex effects produced by KCI applied to the superior vena cava (SVC) and of mechanical distortion of the lungs were also studied. KCI applied to the right or left lung or right or left lung distortion produced significant increases in peak TS-EMG ipsilateral to the applied stimulus with no significant effects on the contralateral TS-EMG. BP, inspiratory time, expiratory time, or peak D-EMG were not significantly affected, except for a decrease in inspiratory time when KCI was applied to the left lung and a decrease in BP with distortion of the left lung. KCI applied to the SVC produced a significant reflex increase in the right TS-EMG. The primary reflex response to chemical stimulation of lung receptors with sympathetic affcrcnts was an increase in expiratory muscle activity. Additionally, mechanical stimulation may also activate these receptors. Furthermore, receptors which produce similar reflex responses are located on the SVC. That tile reflex responses produced by intrathoracic receptors with sympathetic afferents were unilateral suggests that spinal mechanisms are involved. Animal, dog; Lung receptors, with sympathetic afferents; Respiratory muscles, and sympathetic lung afferents; Sympathetic lung afferents, stimulation by KCI; Vagotomy Barry (1913) demonstrated the existence of intrathoracic receptors whose afferent nerves pass through the stellate ganglia. This work has been confirmed by a number of investigators. Insufflation with ammonia or ether (Craigie, 1922), ammonia (Cromer et al., 1933), ammonia or phosgenc (Banister etal., 1949), insufflation with sulphur dioxide or catheter movement in the trachea (Widdicombe, 1954), and inflation of a balloon in the trachea (Rao et al.,
European Respiratory Journal
In guinea-pig isolated airways, nonadrenergic, noncholinergic (NANC) neural responses converge towards a similar level of smooth muscle tone, via a contraction when the tone is low prior to stimulation, and via a relaxation when the tone is high prior to stimulation. We wanted to assess the effect of simultaneous parasympathetic activation on these converging NANC responses, with and without the addition of sympathetic activation. In guinea-pig isolated airways, the spontaneous airway tone was initially abolished by indomethacin (10 microM). In one series, adrenergic depletion by guanethidine (10 microM) was then established, with and without cholinergic blockade by atropine (1 microM). In another series, either cholinergic blockade by atropine (1 microM) or no blockade was utilized. Responses to electrical field stimulation (1,200 mA, 0.5 ms, 3 Hz for 240 s) were studied with no induced tone, at a moderate (0.3 microM) and at a near-maximum (6 microM), histamine-induced tone. The m...
Evidence for nonadrenergic inhibitory nerves in the guinea pig trachealis muscle
The American journal of physiology, 1973
Evidence for nonadrenergic inhibitory nerves in the guinea pig trachealis muscle. Am. J. Physiol. 224(5) : 1072-1080. 1973-The inhibitory innervation of the guinea pig trachealis muscle was studied by placing muscle strips in an organ bath containing Krebs solution equilibrated with 97 y. 02 and 3 To CO2 and measuring the effects of field stimulation on isometric tension in the presence of hyoscine or atropine. In strips obtained from the thoracic trachea: a) relaxations elicited by field stimulation were not sigificantly influenced by propranolol (l-6 1072