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Desmopressin and vasopressin were injected into the blood supply of the bilaterally perfused nasal mucosa of the dog. Nasal vascular resistance and, in some experiments, nasal airflow resistance and the secretory output of the lateral nasal gland were measured on both sides. Systemic arterial blood pressure was recorded. Desmopressin caused a dose-related vasodilation on the side of injection with no changes in systemic arterial blood pressure or secretion by the lateral nasal gland. Nasal airflow resistance did not change significantly. Vasopressin increased nasal vascular resistance on the side of injection with no changes in the systemic arterial blood pressure or secretion by the lateral nasal gland. Nasal airflow resistance did not change significantly. Thus desmopressin dilates the nasal vascular bed and vasopressin constricts it. The relevance of these findings to the use of the two agents applied into the nose in clinical practice is discussed.

The effect of hydrogen peroxide (H 2 O 2 ) was examined on baseline and on methacholine- and phenylephrine-stimulated smooth muscle tone, mucus volume and lysozyme outputs, and epithelial albumin transport of the ferret whole trachea in vitro. H 2 O 2 (10 μM–10 mM) had no significant effect on tracheal smooth muscle tone but produced concentration-dependent increases in mucus volume, lysozyme and albumin outputs. The potential difference (P.D.) across the trachea was not changed by H 2 O 2 . Exposure of the trachea to H 2 O 2 (1 mM) for 2 h reduced the smooth muscle contractions and lysozyme outputs due to methacholine (1 μM) and phenylephrine (10 μM). Methacholine-induced albumin output was significantly increased by H 2 O 2 but that due to phenylephrine was not significantly affected. Exposure to H 2 O 2 had no significant effect on the mucus volume output produced by methacholine or phenylephrine. Thus H 2 O 2 directly stimulates submucosal gland secretion, including secretion from serous cells, and epithelial albumin transport across the ferret trachea but has no effect on tracheal smooth muscle tone. H 2 O 2 reduces methacholine- and phenylephrine-induced smooth muscle contractions and serous cell secretion. H 2 O 2 causes hyperresponsiveness of albumin output to methacholine but not to phenylephrine.

Three groups of airway sensory nervous receptor may be involved in the pathophysiological changes in asthma and allergy. Those most active will be the C-fibre receptors, the rapidly adapting receptors, and A delta-nociceptive receptors. All are stimulated or sensitised by the inflammatory and immunological changes. The C-fibre receptors may mediate the axon reflex neurogenic inflammation-bronchoconstriction, mucus secretion and mucosal hyperaemia due to neuropeptide release-but the evidence for this process in humans, unlike rodents, is scanty. Activation of the receptors will also cause central nervous reflexes. The pathways for these reflexes in the brainstem, where their interactions, and the chemical neurotransmitters involved, are beginning to be delineated. The resulting reflexes include bronchoconstriction, mucus secretion and mucosal vasodilatation, responses that will amplify any similar changes due to neurogenic inflammation. The cough reflex depends on the interaction of the three basic reflex pathways. The reflexes show plasticity at peripheral, ganglionic and central nervous levels, and it is unlikely that results in acute experiments on healthy animals will apply quantitatively to humans with asthma.

The actions of bradykinin and the related compound lys-bradykinin have been studied on the tracheal circulation and tracheal smooth muscle of the sheep. Cranial tracheal arteries of ten anaesthetised and paralysed sheep were isolated and perfused at systemic arterial pressure; arterial inflow was measured with an electromagnetic flow probe. Tracheal smooth muscle tone was assessed by measuring the external diameter of the cranial trachea. Close arterial injection of bradykinin and lys-bradykinin (0.1 to 1000 pmoles) produced potent dose-dependent falls in tracheal vascular resistance: for bradykinin a maximum fall of -56.4% (52.3-60.5%, 95% confidence interval) and for lys-bradykinin -52.8% (46.5-59.1%). The ED50 values were 0.69 (0.51-1.32) and 1.46 (1.19-2.28) pmoles respectively. Small and inconsistent relaxation of tracheal smooth muscle was seen with the higher doses (greater than 1.9 pmoles) of both kinins. Intravenous indomethacin (5 mg.kg-1) increased the vasodilation produced by bradykinin and lys-bradykinin. Oxyhaemoglobin (4 microns at 0.35 ml.min-1) infused into the tracheal circulation almost abolished the responses to bradykinin and methacholine. The results indicate that in the sheep trachea bradykinin has little action on airway smooth muscle but is a potent dilator of the vasculature; bradykinin and lys-bradykinin are of similar potency suggesting the action may be via B2 receptors. While the vascular responses may be modulated by vasoconstrictor cyclo-oxygenase products the vasodilation is likely to be endothelium-dependent and not prostanoid-mediated.

The major pathological changes in rhinitis are vascular, with blood sinus congestion, transudation and oedema, and glandular, with mucus secretion. Both block the nose. Mediators released by antigen-antibody reactions and by inflammatory processes will disrupt nasal function in three main ways. First, mediators such as histamine, bradykinin and leukotrienes will act directly on blood vessels and submucosal glands, causing mucosal thickening and secretion. Second, the same mediators will excite terminals of sensory nervous receptors in the nose, setting up axon reflexes with release of neuropeptides from other branches of the nervous receptors. Neurokinins, such as substance P, will augment vasodilatation and transudation and may modulate the secretions from submucosal glands. Third, the same sensory receptors when stimulated will set up central nervous reflex actions. The responses include sneezing and nasal irritation (both prominent features of rhinitis) reflex nasal vasodilatation and mucus secretion, and actions on the lower airways. The relative importance of these three mechanisms is difficult to assess in man. Successful therapy may act by preventing one of the undesirable motor constituents of rhinitis, or may have a more general action in lessening inflammation or immunological responses.

The volume of an isolated trachea! segment and of the intrathoracic airways (intrathoracic portion of anatomical dead space) were measured during independent changes in ventilation minute volume and alveolar P(;O 2 and PO 2 , in order to assess the separate effects of chemoreceptor and mechanoreceptor signals upon airway calibre. The results were highly dependent upon initial airway tone, initial airway constriction favouring dilator responses and vice versa . Increasing alveolar P CO 2 caused reflex airway constriction if ventilation was held constant. The magnitude of this response was reduced if ventilation was maintained at a high level and increased if it was held at a low level. Increasing ventilation caused reflex airway dilatation even if end tidal P CO 2 was held constant. The size of the dilatation was reduced at high PcO 2 s and increased at low P CO 2 s. The interactions of the chemoreceptor and mechanoreceptor signals and of the effect of initial airway tone put a limit on airway dilatation during hyperventilation and particularly during hypercapnic hyperventilation. These mechanisms also limit the airway constriction following reductions in ventilation. They are consistent with the existence of an airway control system which adjusts airway calibre to minimise the work of breathing.

We have studied defensive reflexes in the ferret. As for the mouse, this species lacks a cough reflex on mechanical stimulation of the tracheal mucosa, and this may be related to the lack of nerves and mucus-secreting cells in the tracheal epithelia of these species. The bronchial cough reflex is similar to that of guinea pigs and rabbits, and the laryngeal reflexes are similar to those in rats

Tidal volume (V t ) and inspiratory (T i ) and expiratory (t e ) durations have been measured in cats anaesthetized with pentobarbitone and exposed to hypercapnia, asphyxia and hypoxia, before and after bilateral vagotomy, mainly using a rebreathing (non-steady state) method. The animals were first artificially ventilated to apnoea. An inverse relationship between V t and T i was always seen, the three stimuli producing identical relationships. After vagotomy none of the cats showed a constant T i with any of the three stimuli. The T e /T i relationship usually occupied two ranges before vagotomy, whereas after vagotomy T e changed little compared with T i . Sudden changes in inspired oxygen concentration changed V t more rapidly than T i , and te more rapidly than T i , both the T i /V t and the T e /T i relationships showing marked “hysteresis”. Increase in body temperature (without “panting”) shifted the T t /V t relationship towards the graphical axes, but the relationship remained hyperbolic whether the vagi were intact or not. The results are interpreted in terms of the influences of vagal lung reflexes and of body temperature on the pattern of breathing.

Minute volume/end-tidal Pco 2 relationships have been determined for anaesthetized and unanaesthetized rabbits, before and after bilateral cervical vagotomy. Vagotomy depresses and flattens the upper parts of the curves (i.e., the ventilatory response to CO 2 is reduced), whether the inspired CO 2 mixture is in air, 100% O 2 or 8–10% O 2 . The increase in frequency of breathing due to CO 2 is especially depressed. During the maximal response to CO 2 the vagotomized rabbits are able to increase ventilation in response to other stimuli. It is concluded that a lung reflex or reflexes is partly responsible for the shape of the minute volume/Pco 2 ; curve in rabbits with intact vagi.

The ventilatory response of a normal human subject to inhalation of a 7 % CO 2 , 93 % O 2 mixture was studied. Following bilateral block of the vagus and glossopharyngeal nerves with 1 % lignocaine, the ventilatory response to CO 2 was diminished and this effect was associated with failure of the respiratory rate to increase as in the control experiment. This effect was thought to be due to block of vagal afferent fibres from the lungs. It was not thought to be due to chemoreceptor block because animal experiments have shown that inhalation of a high concentration of O 2 suppresses the sensitivity of peripheral chemoreceptors to hypereapnia. The typical respiratory distress associated with rebreathing CO 2 was abolished by the nerve block.

Changes in the volume of an isolated innervated segment of trachea, minute volume, heart rate and blood pressure have been measured during stimulation of the medullary “respiratory centres” of anaesthetised dogs. Changes in ventilation were nearly always accompanied by changes in tracheal volume. The changes in tracheal volume were not solely the reflex effect of the changes in ventilation, since they occurred in paralysed animals artificially ventilated at fixed levels. Paralysis often reversed, but never eliminated, the tracheal response to stimulation at a particular site. Tracheal responses were highly dependent on the frequency of stimulation, high frequencies tending to lead to dilatation, low to constriction. This frequency-dependent effect was observed less commonly with the respiratory response and rarely with the cardiovascular response. There were no correlations between sites of stimulation and respiratory, tracheal or cardiovascular responses.

Summary The belief that tuberculosis and insanity were incompatible arose in the middle of the eighteenth century pari passu with the widespread use of the strait-waistcoat in psychiatric practice, and disappeared with its disuse in the middle of the nineteenth century. Evidence is presented that this belief may have arisen from the pneumoperitoneum-like effect of the strait-waistcoat, which may thus have constituted an unrecognised form of collapse therapy.

The effect of peripheral chemoreceptor denervation was studied during bilateral block of the vagus and glossopharyngeal nerves with 1 % lignocaine in a healthy conscious subject. This procedure resulted in almost complete abolition of the hyperventilation which occurs when breathing a hypoxic gas mixture.

Publisher Summary Most parts of the lungs and airways, but not the nose, are distensible and contain proprioceptors in their walls. However, distension and collapse will also affect afferent information from the surrounding somatic muscles of breathing, and the volume change may be initiated by the contraction of these muscles. Therefore, it is not always easy to determine the site of origin of the proprioceptive sensation: most analytical studies have depended on the nervous blockade by local anaesthesia or by disease. This chapter discusses the respiratory proprioception that can be of pressure, volume, flow, ventilation or loading, elastic or resistive loads frequently being studied. A mouthpiece or nose-clip is usually used, thus distorting an important part of the airway sensing system. Flow and pressure can certainly be detected in the nose and mouth, but there is little evidence for their detection more peripherally.

Publisher Summary This chapter discusses the modes of excitation of respiratory tract receptors. Surface-acting chemical and mechanical irritants applied to different parts of the respiratory epithelium can elicit powerful reflexes of many different patterns—sneezing, coughing, and apnoeas. These reflexes are because of stimulation of epithelial irritant receptors. The main method for studying the physiology of the receptors is by recording action potentials from single fibres from individual receptors, and by testing the conditions that set up or change this impulse traffic. All the receptors, from nose to small bronchi, have many features in common: all are mechanosensitive; nearly all are sensitive to chemical irritants; rapidly adapt to a maintained mechanical stimulus—that is, their firing frequency slows considerably or stops altogether within a few seconds; most of them have very irregular and random discharge patterns; and many of the endings show an off-response when the stimulus is removed.