Slowly Adapting Stretch Receptors Research Articles

Airway mechanoreceptor deactivation

Airway sensors play an important role in control of breathing. Recently, it was found that pulmonary slowly adapting stretch receptors (SARs) cease after a brief excitation following sodium pump blockade by ouabain. This deactivation can be explained by overexcitation. If this is true, mechanical stimulation of the SARs should also lead to a deactivation. In this study, we recorded unit activity of the SARs in anesthetized, open-chest, and mechanically ventilated rabbits and examined their responses to lung inflation at different constant pressures. Forty-seven of 137 units had a clear deactivation during the lung inflation. The deactivation threshold varied from unit to unit. For a given unit, the higher the inflation pressure, the sooner the deactivation occurs. For example, the SARs deactivated at 3.0 +/- 0.3 and 4.8 +/- 0.4 s when the lungs were inflated to constant pressures of 30 and 20 cmH(2)O, respectively (n = 25, P < 0.0001). The units usually ceased after a brief intense discharge. In some units, their activity shifted to a lower level, indicating a pacemaker switching. Our results support the notion that SARs deactivate due to overexcitation.

Physiology of long pranayamic breathing: Neural respiratory elements may provide a mechanism that explains how slow deep breathing shifts the autonomic nervous system

Pranayamic breathing, defined as a manipulation of breath movement, has been shown to contribute to a physiologic response characterized by the presence of decreased oxygen consumption, decreased heart rate, and decreased blood pressure, as well as increased theta wave amplitude in EEG recordings, increased parasympathetic activity accompanied by the experience of alertness and reinvigoration. The mechanism of how pranayamic breathing interacts with the nervous system affecting metabolism and autonomic functions remains to be clearly understood. It is our hypothesis that voluntary slow deep breathing functionally resets the autonomic nervous system through stretch-induced inhibitory signals and hyperpolarization currents propagated through both neural and non-neural tissue which synchronizes neural elements in the heart, lungs, limbic system and cortex. During inspiration, stretching of lung tissue produces inhibitory signals by action of slowly adapting stretch receptors (SARs) and hyperpolarization current by action of fibroblasts. Both inhibitory impulses and hyperpolarization current are known to synchronize neural elements leading to the modulation of the nervous system and decreased metabolic activity indicative of the parasympathetic state. In this paper we propose pranayama's physiologic mechanism through a cellular and systems level perspective, involving both neural and non-neural elements. This theoretical description describes a common physiological mechanism underlying pranayama and elucidate the role of the respiratory and cardiovascular system on modulating the autonomic nervous system. Along with facilitating the design of clinical breathing techniques for the treatment of autonomic nervous system and other disorders, this model will also validate pranayama as a topic requiring more research.

Neuroepithelial bodies not connected to pulmonary slowly adapting stretch receptors

Neuroepithelial bodies (NEBs) are believed to be connected with one of the known types of airway receptors. The present studies determined whether NEB afferents are pulmonary slowly adapting stretch receptors (SARs). NEBs are immunoreactive with antibodies against protein gene product (PGP) 9.5 and calcitonin gene-related peptide (CGRP), whereas SARs are reactive with antibody to Na(+)/K(+)-ATPase. Using histochemical staining in combination with confocal microscopy, we compared the morphology of NEBs and SARs in the rat. Our results show that NEBs and SARs are different in location, size, and shape. Double staining of airway tissues for PGP (or CGRP) plus Na(+)/K(+)-ATPase shows that NEBs and SARs do not co-localize. In addition, we electrophysiologically recorded single-unit activity of SARs from the cervical vagus nerve, identified their receptive fields, dissected them into blocks, and then double-stained and examined the receptor structures. We found that the blocks contain the SAR, but not NEB structures. Thus, we conclude that NEBs are not connected to SARs.

Bronchopulmonary afferent nerves.

Vagal afferent nerves are the primary communication pathways between the bronchopulmonary system and the central nervous system. Input from airway afferent nerves to the CNS is integrated in the brainstem and ultimately leads to sensations and various reflex outputs. Afferent nerves innervating the airways can be classified into various distinct phenotypes. However, there is no single classification scheme that takes all features, including conduction velocity, cell body diameter, ganglionic origin, and stimuli to which they respond (modality) into account. At present, bronchopulmonary afferent nerves are typically considered to belong to one of three general categories, namely C-fibres, rapidly adapting stretch receptors (RARs), and slowly adapting stretch receptors (SARs). As our understanding of bronchopulmonary afferent nerves continues to deepen, we are likely to see more sophisticated classification schemes emerge. It is clear that the function of afferent fibres can be substantively influenced by airway inflammation and remodelling. The perturbations and perversions of afferent nerve function that occur during these states almost certainly contributes to many of the signs and symptoms of inflammatory airway disease. A more lucid characterization of bronchopulmonary afferent nerves, and a better understanding of the mechanisms by which these nerves influence pulmonary physiology during health and disease anticipates future research.

Lung vagal afferent activity in rats with bleomycin-induced lung fibrosis

Bleomycin treatment in rats results in pulmonary fibrosis that is characterized by a rapid shallow breathing pattern, a decrease in quasi-static lung compliance and a blunting of the Hering–Breuer Inflation Reflex. We examined the impulse activity of pulmonary vagal afferents in anesthetized, mechanically ventilated rats with bleomycin-induced lung fibrosis during the ventilator cycle and static lung inflations/deflations and following the injection of capsaicin into the right atrium. Bleomycin enhanced volume sensitivity of slowly adapting stretch receptors (SARs), while it blunted the sensitivity of these receptors to increasing transpulmonary pressure. Bleomycin treatment increased the inspiratory activity, while it decreased the expiratory activity of rapidly adapting stretch receptors (RARs). Pulmonary C-fiber impulse activity did not appear to be affected by bleomycin treatment. We conclude that the fibrosis-related shift in discharge profile and enhanced volume sensitivity of SARs combined with the increased inspiratory activity of RARs contributes to the observed rapid shallow breathing of bleomycin-induced lung fibrosis.

Lung congestion augments the responses of cells in the rapidly adapting receptor pathway to cigarette smoke in rabbit.

1. We examined the effects of cigarette smoke, inhaled alone and during mild pulmonary venous congestion, on the activity of fifty-three neurones in the nucleus tractus solitarii (NTS) that were excited by input from pulmonary rapidly adapting receptors (RAR). Ten neurones excited by slowly adapting stretch receptors (SAR) were also studied. 2. Extracellular recordings of RAR-activated neurones were recorded in alpha-chloralose anaesthetized rabbits. Smoke from low- and high-nicotine cigarettes was delivered through a ventilator. Mild pulmonary venous congestion was produced by inflating a balloon in the left atrium. 3. Inhalation of three breaths of smoke from low-nicotine cigarettes increased the activity of fifty-one out of fifty-three RAR-activated neurones from 5.9 +/- 1.0 to 14.4 +/- 2.1 spikes breath-1 (P < 0.05). 4. The responses of fifteen neurones were compared with smoke inhaled alone or during mild pulmonary venous congestion. Smoke alone increased unit activity from 6.8 +/- 2.3 to 12.6 +/- 3.7 spikes breath-1 (P < 0.05). Small increases in left atrial pressure (2.0 +/- 0.5 mmHg) had no effect on baseline unit activity (7.6 +/- 2.11 vs. 7.7 +/- 2.3 spikes breath-1; P > 0.05), but enhanced the responses to smoke, increasing the activity from 7.6 +/- 2.1 to 17.1 +/- 4.8 spikes breath-1 (P < 0.05). The response was greater than to smoke alone (P < 0.05). 5. Of ten SAR-activated neurones, seven failed to respond to inhaled cigarette smoke, two were excited and one was inhibited. Pulmonary venous congestion had no effect on the unit activity before and after smoke (n = 4 neurones). 6. We conclude that smoke-evoked excitation of RAR lower-order neurones is augmented by pulmonary venous congestion.

Heterogeneous activity of pulmonary vagal receptors during high-frequency oscillation ventilation.

The purpose of the study was to examine the response of vagal pulmonary slowly adapting stretch receptors (SAR) to high-frequency oscillation ventilation (HFO) in rabbits by analyzing the afferent activity recorded in vagal single-fiber preparations. The vagal afferent activity was recorded during short runs of HFO with a stroke volume of 2-3 ml/kg applied at oscillation frequencies (fosc) of 5, 10, 15, 20, and 25 Hz and each frequency at three levels of mean airway pressure (P(aw)), namely, 1, 3, and 8 cm H2O. The receptor discharge rates during HFO were compared with those during quiet spontaneous breathing as well as during static lung inflations and deflations. The majority of SAR was stimulated by HFO, however, the SAR discharge patterns during HFO were less homogeneous than during static lung inflations. The heterogeneity of SAR responses to HFO became pronounced with increasing P(aw) and fosc. From the results, we conclude that HFO elicits heterogeneous discharge patterns of SAR, but the previously reported heterogeneity of responses of rapidly adapting receptors was even greater. This heterogeneity of vagal activity is probably the result of heterogeneous mechanical conditions within the lungs during HFO and may, in turn, give rise to the various types of respiratory reflex responses to HFO.

Responses of tracheobronchial receptors to halothane, enflurance, and isoflurane in anesthetized dogs

We investigated the effects of halothane, enflurane, and isoflurane on the activity of 43 tracheo-bronchial slowly adapting stretch receptors (SARs) and 16 rapidly adapting irritant receptors (RARs) in 5 anesthetized, vagotomized, paralyzed, and artificially ventilated dogs. The 43 SARs were classified into 2 subtypes: (i) 17 low-threshold SARs with an expiratory discharge at FRC that were active throughout the respiratory cycle and (ii) high-threshold SARs active only in respiration. Ventilating the lungs with 5% of each anesthetic caused a significant increase in the inspiratory discharge of low-threshold SARs, whereas the expiratory discharge was inhibited or altogether silenced. While the activity of the majority of high-threshold SARs increased during the administration of the three volatile anesthetics, it decreased in those with a particulary high recruitment threshold. There was however, a consistent increase in the pressure threshold at which all SARs were recruited. Ventilating the lungs with 5% of each anesthetic cuased a significant decrease in activity of RARs. Our results indicate that all three halogenated anesthetics inhibit RAR at concentrations rangig from 1% to 5%.

Afferent neural pathways in cough and reflex bronchoconstriction.

Cough and bronchoconstriction are airway reflexes that protect the lung from inspired noxious agents. These two reflexes can be evoked both from the larynx and tracheobronchial tree and also from some extrarespiratory sites. Within the airways, certain sites are particularly sensitive to stimulation of cough (larynx and points of proximal airway branching), whereas bronchoconstriction can be triggered from the whole of the tracheobronchial tree. In the larynx, "irritant" receptors with myelinated afferents mediate cough and bronchoconstriction. Little seems to be known about laryngeal nonmyelinated afferents and their reflexes. In the tracheobronchial tree and lung, slowly adapting stretch receptors (SARs) and rapidly adapting stretch receptors (RARs) have opposing effects on airway tone, the former mediating bronchodilation and the latter bronchoconstriction. In cough, on the other hand, they operate concurrently, a mediatory role for RARs and a facilitatory role for SARs. C-fiber endings (bronchial and pulmonary) mediate bronchoconstriction. Inhalation of so-called "selective" C-fiber stimulants induces cough, but excitation of RARs has not been eliminated, and the possibility also exists that the cough is secondary to other lung actions mediated by these nerve endings. Although cough and bronchoconstriction may be mediated by the same type of receptor, they seem to have separate afferent neural pathways.

Effects of airway cooling on tracheal stretch receptors

We studied the effect of cold air on tracheal slowly adapting stretch receptors (SAR) in 6 anesthetized, spontaneously breathing dogs. Air at constant flow and two different temperatures was passed through an isolated segment of the extrathoracic trachea. We recorded SAR action potentials, esophageal pressure, tracheal pressure and temperature. With a reduction in tracheal temperature of ≈10 °C the steady state response of 30 SARs to a distending pressure of 1.0 kPa decreased to 75% of control (P < 0.001). At lower distending pressure the inhibitory effect of tracheal colling decreased: 87% of control at 0.5 kPa (P < 0.05, n = 8) and 96% of control at 0.2 kPa (P > 0.05, n = 8). The response of 13 tracheal SARs to sinusoidal pressure oscillations (0.15 kPa) superimposed on a bias pressure (0.5 kPa) was reduced (P < 0.01) by local cooling to the same extent at the 2 pressure extremes ( ‘peak’ value = 71% of control; ‘valley’ = 67% of control), resulting in a similar change in receptor discharge within the oscillatory cycle. The inhibitory effect of airway cooling on stretch receptors may play a role in cold-induced bronchoconstriction.

Effect of nicotine aerosol on slowly adapting receptors in the airways of the dog.

The response of slowly adapting airway stretch receptors to nicotine aerosol was studied in the paralyzed, artificially ventilated, anesthetized dog. Single-unit stretch receptor recordings were made from individual vagus nerve filaments placed on a pair of platinum hook electrodes. Administration of 2% nicotine aerosol for five consecutive breaths caused an increase in both the peak transpulmonary pressure (Ptp) and in the activity of the slowly adapting stretch receptors (SARs). The results suggest that tracheal SARs were more affected than those receptors located distal to the carina. Administration of nicotine aerosols following pretreatment with isoproterenol, a bronchodilator, failed to significantly increase Ptp and, concomitantly, the activity of SARs. Therefore, the stimulatory effect of nicotine on SARs appeared to involve primarily an indirect activation of SARs via nicotine-induced bronchoconstriction. It is suggested that the activation of SARs may be involved in the reported nicotine-dependent cigarette smoke-induced apnea.

Breathing pattern and diaphragm EMG after SO 2 in rabbit intra- or extrathoracic airways

In anesthetized rabbits under SO 2 block of slowly adapting stretch receptors (SAR) in intrathoracic airways Ti increased by 49.7 ± 6.9% and Vt by 19.5 ± 3.7% . Te decreased for small increases of Ti and vice versa. Slope of moving average of diaphragm EMG (M.A.) decreased by 16.7 ± 4.1% from 0 to 30% Ti control, and increased by 26.3 ± 8.1% from 30 to 70%. Considering that discharge from intrathoracic SAR increases during inspiration, these changes of M.A. indicate that their input facilitates inspiration at its beginning, but inhibits it later on, in line with previous conclusions based on SAR block which included 2 3 of extrathoracic trachea (ETT). Neither SO 2 nor pressures from −40 to ±40 cm H 2O in ETT changed breathing pattern or M.A.. Hence, SAR of ETT do not affect parameters studied in rabbits. When extrathoracic airways were exposed to SO 2 Ti increased by 30.5 ± 8.2%, Te by 37.9 ± 5.1% , Vt did not change. Hence, some receptors rostral to trachea, involved in respiratory control, are affected by SO 2.

Stimulation of tracheal slowly adapting stretch receptors by hypercapnia and hypoxia

We studied the response of tracheal slowly adapting stretch receptors (SARs), whose activity was recorded from the peripheral cut end of the right vagus nerve, in newborn and adult dogs during hyperoxic hypercapnia and isocapnic hypoxia. Tracheal receptors only were studied since it was possible to maintain the parasympathetic efferent supply partially intact (contralateral vagus nerve and superior laryngeal nerve). The animals were anesthetized and passively ventilated with the chest open. A stimulatory effect was found in 9 out of 20 puppies for hypercapnia and in 3 out of 10 for hypoxia. The maximum amount of stimulation ranged from 114 to 556% of the control discharge for hypercapnia and from 110 to 387% for hypoxia. In the adult dog CO 2 stimulated tracheal SARs in 11 out of 16 dogs (103–404% control) while hypoxia stimulated SARs in 9 out of 13 animals (109–268% control). The stimulatory effect was greater during expiration and for hypercapnia, decreased in intensity with time. This excitatory action was eliminated by cold block of the contralateral vagus nerve or atropine administration, suggesting that the stimulation was mediated by smooth muscle contraction. These findings support the notion that airway stretch receptors are activated not only by passive distension of the airways, but also by an active contraction of the tracheobronchial smooth muscle.

Topical anesthesia of tracheal receptors.

Two types of sensory receptors were individually identified in dogs on the exposed mucosa of the extrathoracic trachea: slowly adapting stretch receptors (SAR) and rapidly adapting receptors (RAR). Increasing concentrations of lidocaine (L), bupivacaine (B), and tetracaine (T) solutions were topically applied on the mucosa over the sensory fields of the receptors, while their neural activity in response to an appropriate stimulus was recorded. Action potentials from SARS were blocked by the anesthetic at a much higher concentration and with larger exposure times than potentials evoked from RARs (mean values: L = 51.1 mM for 7.4 min and 1.48 mM for 1.03 min, respectively; B = 9.4 mM for 9.4 min and 0.13 mM for 0.23 min; and T = 4.9 mM for 9.8 min and 0.06 mM for 2 min). The minimal blocking concentration of the topical anesthetics varied widely (L = 20 times, B = 5, and T = 5) among SARs and less (L = 3.2, B = 2, and T = 4) among RARs. These results could be explained by a different location in the mucosa of the two types of receptors and suggest the feasibility of a differential blockade by topical anesthetics.

II. Effect of CO 2 on afferent vagal endings in the canine lung

We have attempted to identify the afferent endings responsible for the pulmonary-CO 2 ventilatory reflex. We recorded afferent vagal impulses arising from the left lung in anesthetized dogs with separately ventilated lungs. When the left pulmonary artery was occluded, left lung P CO 2 fell to 3 mm Hg and slowly-adapting pulmonary stretch receptor activity increased 46%. Firing declined to its original intensity when left lung P CO 2 was raised in steps by administration of CO 2, firing decreasing most between 2 and 19 mm Hg, and least between 30 and 50 mm Hg. Irritant receptor activity also increased (from 2.8 to 7.4 impulses/sec) after pulmonary arterial occlusion, the effect being reversed by administration of CO 2. These procedures caused trivial changes in pulmonary and bronchial C-fiber activity. Effects on both slowly-adapting stretch receptors and irritant receptors appeared to result from a direct action of CO 2 on the endings themselves, rather than from mechanical changes in the lung. Changes in slowly-adapting stretch receptor activity provide an adequate explanation for the pulmonary CO 2 ventilatory reflex, the relationship between impulse frequency and lung P CO 2 suggesting that these afferents may have a role in limiting CO 2 loss under conditions causing hypocapnia, but be less effective in stimulating breathing during hypercapnia.

Reflex inhibition of the slowly adapting stretch receptors in the intact abdomen of the crayfish.

The reflex inhibition of abdominal stretch receptors in crayfish was studied by controlled passive flexion of individual abdominal joints. The results are very similar to those obtained by electrical or mechanical stimulation of individual stretch receptors in immobilized abdomens. Reflex effects from posterior to anterior abdominal segments are somewhat stronger than in the opposite direction. Flexion of one abdominal joint excites the stretch receptors of that joint and inhibits the stretch receptors in neighbouring abdominal segments. Without reflex inhibition flexion of one abdominal joint excites the stretch receptors in several abdominal segments.

On the Operation of Transfusion in Obstetric Practice: With Description of a More Convenient Transfusion-Apparatus

<b>Rationale</b>. Inhibition of slowly adapting stretch receptors (SARS) inhibits the cough reflex (CR), but it is not clear whether SARS stimulation facilitates CR and/or expiration reflex (ER). The issue is relevant to the long term understanding of chronic cough because those mechanisms that regulate cough are poorly understood. The <b>aim of the study</b> was to demonstrate whether SARS stimulation by continuous positive airway pressure (CPAP) alters CR and/or ER in the rabbit. <b>Methods</b>: 5 rabbits were anesthetized and tracheostomized. The trachea was exoposed to punctuate mechanical stimuli at control and with 4-5 hPa CPAP. 24 stimulations were aimed in each condition in each animal. CR and ER were identified from airflow and volume signals, diaphragmatic and abdominal muscle electrical activity. The reflexes were defined as a forced expiratory effort preceded (CR) or not (ER) by an augmented inspiration. Mixed responses were differentiated from the pattern of the first breath as ER/CR and CR/ER. <b>Results:</b> 241 stimulations, evenly distributed in inspiration and expiration, were obtained at control (n = 121) and on CPAP (n = 120). The overall incidence of positive responses significantly increased from 66% at control to 85% on CPAP (p = 0.0005). Incidence of ER, CR or CR/ER was not significantly altered. In contrast the mixed ER/CR response significantly increased from 14% at control to 38% on CPAP (p = 0.0005). <b>Conclusions</b>. SARS stimulation up regulates airway defensive reflexes, namely ER/CR. Thus SARS appear to sensitize preferentially those ER-facilitated coughs. It is speculated that a proper identification of airway defensive responses in patients may be relevant to a better understanding of chronic cough.