A historical perspective of pulmonary rapidly adapting receptors.

Bronchopulmonary mechanosensors play an important role in the regulation of breathing and airway defense. Regarding the mechanosensory unit, investigators have conventionally adhered to 2 doctrines: one-sensor theory (one afferent fiber connects to a single sensor) and line-labeled theory. Accordingly, lung inflation activates 2 types of mechanosensors: slowly adapting receptors (SARs) and rapidly adapting receptors (RARs) that also respond to lung deflation to produce Hering-Breuer deflation reflex. RARs send signals to a particular brain region to stimulate breathing (labeled as excitatory line) and SARs to a different region to inhibit breathing (inhibitory line). Conventionally, RARs are believed to be mechanosensors, but are also stimulated by a variety of chemicals and mediators. They are activated during different disease conditions and evoke various respiratory responses. In the literature, RARs are the most debatable sensors in the airway. Recent physiological and morphological studies demonstrate that a mechanosensory unit consists of numerous sensors with 4 types, i.e., an afferent fiber connects to multiple homogeneous or heterogeneous sensors (multiple-sensor theory). In addition to SARs and RARs, there are deflation-activated receptors (DARs), which can adapt slowly or rapidly. Each type senses a specific force and generates a unique response. For example, RAR (or SAR) units may respond to deflation if they house DARs responsible for the Hering-Breuer deflation reflex. Multiple-sensor theory requires a conceptual shift because 4 different types of information from numerous sensors carried in an afferent pathway violates conventional theories. Data generated over last eight decades under one-sensor theory require re-interpretation. Mechanosensors and their reflex functions need re-definition. This detailed review of the RARs represents our understanding of RARs under the conventional doctrines, thus it provides a very useful background for interpretation of RAR properties and reflex function against the new proposed multiple-sensor theory.

Neonatal stress and abnormal hypercapnic ventilatory response of adult male rats: the role of central chemodetection and pulmonary stretch receptors.

Neonatal maternal separation (NMS) is a form of stress that interferes with respiratory control development. At adulthood, the hypercapnic ventilatory response (HCVR) of male NMS rats is lower than controls both during wakefulness and anesthesia. To address the mechanisms underlying the respiratory phenotype of NMS rats, we first used phrenic nerve recording in anesthetised (urethane: 1.0 g/kg+isoflurane: 0.5%), vagotomised, and artificially ventilated (hyperoxic) animals, to test the hypothesis that the central chemodetection is altered by NMS. As no difference was observed between groups, we then tested the hypothesis that NMS affects respiratory modulation by pulmonary stretch receptors (PSRs). Experiments were performed on urethane/isoflurane anesthetised, spontaneously breathing rats (with vagi intact). The role of PSR and their implication was assessed during normo- and hypercapnia (+10 mm Hg above baseline) by the induction of a positive airway pressure (Paw). The slopes of the relationships between the ventilatory variables (frequency, amplitude, and minute activity) and the different levels of Paw in each group were compared between groups. During normocapnia, the decrease in breathing frequency induced by increasing Paw was greater in control than in NMS rats, thereby revealing that NMS reduces the Hering-Breuer reflex (HBR). During hypercapnia, however, the responses of control and NMS rats were similar indicating that the stimulation of chemoreceptors by CO(2) reduced the influence of stretch receptors on ventilation. These results indicate NMS does not affect central CO(2) chemosensitivity of this preparation but that differences in PSR function and/or signal integration contribute to the effects of NMS on respiratory regulation.

Downregulation of cough by exercise and voluntary hyperpnea.

No information exists on the effects of hyperpnea on the sensory and cognitive aspects of coughing evoked by inhalation of tussigenic agents. The threshold for the cough reflex induced by inhalation of increasing concentrations of ultrasonically nebulized distilled water (fog), and the index of cough reflex sensitivity, was assessed in 12 healthy humans in control conditions, during exercise, and during voluntary isocapnic hyperventilation (VIH) to the same level as the exercise. The intensity of the urge-to-cough (UTC), a cognitive component of coughing, was also recorded throughout the trials. The log-log relationship between inhaled fog concentrations and the correspondingly evoked UTC values, an index of the perceptual magnitude of the UTC sensitivity, was also calculated. Cough appearance was always assessed audiovisually. At an exercise level of 80% of anaerobic threshold, the mean cough threshold was increased from a control value of 1.03 +/- 0.65 to 2.25 +/- 1.14 ml/min (p < 0.01), i.e., cough sensitivity was downregulated. With VIH, the mean (+/-SD) threshold increased from 1.03 +/- 0.65 to 2.42 +/- 1.16 ml/min (p < 0.01), a similar downregulation. With exercise and VIH compared with control, mean UTC values at cough threshold were not significantly changed: control, 3.83 +/- 1.11 cm; exercise, 3.12 +/- 0.82 cm; VIH, 4.08 +/- 1.67 cm. Since the slopes of the log fog concentration/log UTC value were approximately halved during exercise and VIH compared with control, the UTC sensitivity to fog was depressed (p < 0.01). The results indicate that the adjustments brought into action by exercise-induced or voluntary hyperventilation exert inhibitory influences on the sensory and cognitive components of fog-induced cough.

[Relationship of stress index with lung recruitment and gas exchange in dogs with acute respiratory distress syndrome].

OBJECTIVE: To determine the relationship of stress index with lung recruitment and gas exchange in dogs with acute respiratory distress syndrome (ARDS). METHODS: The ARDS model was induced by infusion of oleic acid intravenously in anesthetized dogs. During volume control ventilation with constant inspiratory flow, the pressure-time (P-t) curve was fitted to a power equation: P = a.time(b)+c, where coefficient b (stress index) describes the shape of the curve: b = 1, straight curve; b < 1, progressive increase in slope; and b > 1, progressive decrease in slope. Tidal volume (V(T)) was 6 ml/kg, and positive end-expiratory pressure (PEEP) was set to obtain a b value between 0.9 and 1.1 before (b = 1) and after (b = 1 after recruiting maneuver) application of a recruiting maneuver (RM). PEEP was changed to obtain 0.6 < b < 0.8 and 1.1 < b < 1.3. Experimental condition sequence was random. Recruited volume (RV) was measured by static pressure-volume curve method. Hemodynamics, pulmonary mechanics and gas exchange were observed at the same time. RESULTS: At b = 1 without RM, the PEEP was (5.0 +/- 3.0) cm H2O, the RV was (27 +/- 15) ml, and the RV increased to (166 +/- 84) ml significantly at b = 1 after RM [PEEP (10.8 +/- 2.3) cm H2O (1 cm H2O = 0.098 kPa), q = 3.18, P < 0.01]. At 1.1 < b < 1.3 after RM, the PEEP was (16.8 +/- 1.1) cm H2O and the RV was (262 +/- 57) ml, which was higher than that at b = 1 after RM (q = 2.54, P = 0.023). At 0.6 < b < 0.8 after RM, the PEEP was (5.6 +/- 2.2) cm H2O and the RV was lower than that at b = 1 after RM (q = 2.85, P = 0.013). The partial pressure of oxygen in arterial blood (PaO2) in b = 1, 0.6 < b < 0.8 and 1.1 < b < 1.3 after RM were (319 +/- 49) mm Hg (1 mm Hg = 0.133 kPa), (246 +/- 57) mm Hg and (314 +/- 27) mm Hg respectively, which was higher than the PaO2 at b = 1 without RM [(153 +/- 64) mm Hg, all q = 2.81, all P < 0.05]. The PaO2 at 0.6 < b < 0.8 was lower than that at b = 1 after RM (q = 2.81, P = 0.005), while there was no significant difference between the PaO2 at 1.1 < b < 1.3 and that at b = 1 after RM. The peak airway pressure and plateau pressure at 1.1 < b < 1.3 were higher than those at b = 1 after RM (q = 6.02, 5.72, all P < 0.05). CONCLUSION: In the b = 1 after RM, there were better PaO2 and lower airway pressure, suggesting that b = 1 after RM may be a good indicator for PEEP titration.

Maintained inspiratory activity during proportional assist ventilation in surfactant-depleted cats early after surfactant instillation: phrenic nerve and pulmonary stretch receptor activity.

BACKGROUND: Inspiratory activity is a prerequisite for successful application of patient triggered ventilation such as proportional assist ventilation (PAV). It has recently been reported that surfactant instillation increases the activity of slowly adapting pulmonary stretch receptors (PSRs) followed by a shorter inspiratory time (Sindelar et al, J Appl Physiol, 2005 [Epub ahead of print]). Changes in lung mechanics, as observed in preterm infants with respiratory distress syndrome and after surfactant treatment, might therefore influence the inspiratory activity when applying PAV early after surfactant treatment. OBJECTIVE: To investigate the regulation of breathing and ventilatory response in surfactant-depleted young cats during PAV and during continuous positive airway pressure (CPAP) early after surfactant instillation in relation to phrenic nerve activity (PNA) and the activity of PSRs. METHODS: Seven anesthetized, endotracheally intubated young cats were exposed to periods of CPAP and PAV with the same end-expiratory pressure (0.2-0.5 kPa) before and after lung lavage and after surfactant instillation. PAV was set to compensate for 75% of the lung elastic recoil. RESULTS: Tidal volume and respiratory rate were higher with lower PaCO2 and higher PaO2 during PAV than during CPAP both before and after surfactant instillation (p < 0.05; both conditions). As an indicator of breathing effort, esophageal deflection pressure and PNA were lower during PAV than during CPAP in both conditions (p < 0.02). Peak PSR activity was higher and occurred earlier during PAV than during CPAP (p < 0.01), and correlated linearly with PNA duration in all conditions studied (p < 0.001). The inspiratory time decreased as tidal volume increased when CPAP was changed to PAV, with the highest correlation observed after surfactant instillation (r = -0.769). No apneic periods could be observed. CONCLUSION: PSR activity and the control of breathing are maintained during PAV in surfactant-depleted cats early after surfactant instillation, with a higher ventilatory response and a lower breathing effort than during CPAP.

Airway sensory innervation as a target for novel therapies: an outdated concept?

Sensory nerves in the airways regulate central and local reflex events such as bronchoconstriction, airway plasma leakage, mucus secretion and cough. Sensory nerve activity can be enhanced during inflammation and, as a result, these protective reflexes become exacerbated and deleterious. The development of drugs that directly inhibit sensory nerve function has again become an attractive target for the pharmaceutical industry. In particular, the focus is on inhibition of the symptoms associated with airway inflammatory diseases such as asthma, chronic obstructive pulmonary disease and cough of any aetiology.

Responses of C fiber afferents of the rabbit airways and lungs to changes in extra-vascular fluid volume.

Effects of changes in extra-vascular fluid volume produced by pulmonary lymphatic obstruction and plasmapheresis on the activities of bronchial and pulmonary C fiber receptors and rapidly adapting receptors (RARs) were investigated in New Zealand White rabbits. In intact rabbits, pulmonary lymphatic obstruction either alone or in combination with plasmapheresis did not stimulate pulmonary C fiber receptors. Only the combined stimulus activated the bronchial C fiber receptors. Bronchial C fiber receptors were also stimulated by graded increases in left atrial pressure (+5 and +10 mmHg). In contrast, RARs were activated by lymphatic obstruction either alone or in combination with plasmapheresis. These procedures increase the extra-vascular fluid volume in the carina and bronchi but not in the lungs (alveoli). In rabbits with chronic pulmonary venous congestion secondary to mitral valve damage, bronchial C fiber receptors were not stimulated by these increments in left atrial pressure which were insufficient to increase the extra vascular fluid content of the airways. However, both pulmonary and bronchial C fiber receptors were stimulated when the left atrial pressure was raised to 25 mmHg in these animals to cause pulmonary edema.

Activation of lung vagal sensory receptors by circulatory endotoxin in rats.

Although endotoxin is known to induce various pulmonary responses that are linked to the function of lung vagal sensory receptors, its effects on these pulmonary receptors are still not clear. This study investigated the effects of circulatory endotoxin on the afferent activity of lung vagal sensory receptors in rats. We recorded afferent activity arising from vagal pulmonary C fibers (CFs), rapidly adapting receptors (RARs), tonic pulmonary stretch receptors (T-PSRs), and phasic pulmonary stretch receptors (P-PSRs) in 64 anesthetized, paralyzed, and artificially ventilated rats. Intravenous injection of endotoxin (50 mg/kg; lipopolysaccharide) stimulated 7 of the 8 CFs, 8 of the 8 RARs, and 4 of the 8 T-PSRs studied, while having no effect on the 8 P-PSRs tested. The stimulation started 3-16 min after endotoxin injection and lasted until the end of the 90-min observation period. The evoked discharge of either CFs or RARs was not in phase with the ventilatory cycle, whereas that of T-PSRs showed a respiratory modulation. Injection of a saline vehicle caused no significant change in the discharge of these receptors. Additionally, endotoxin significantly produced an increase in total lung resistance, and decreases in dynamic lung compliance and arterial blood pressure. Our results demonstrate that a majority of lung vagal sensory receptors are activated following intravenous injection of endotoxin, and support the notion that these pulmonary receptors may function as an important afferent system during endotoxemia.

PET(CO(2)) inversely affects MSNA response to orthostatic stress.

Arterial hypocapnia has been associated with orthostatic intolerance. Therefore, we tested the hypothesis that hypocapnia may be detrimental to increases in muscle sympathetic nerve activity (MSNA) and total peripheral resistance (TPR) during head-up tilt (HUT). Ventilation was increased approximately 1.5 times above baseline for each of three conditions, whereas end-tidal PCO(2) (PET(CO(2))) was clamped at normocapnic (Normo), hypercapnic (Hyper; +5 mmHg relative to Normo), and hypocapnic (Hypo; -5 mmHg relative to Normo) conditions. MSNA (microneurography), heart rate, blood pressure (BP, Finapres), and cardiac output (Q, Doppler) were measured continuously during supine rest and 45 degrees HUT. The increase in heart rate when changing from supine to HUT (P < 0.001) was not different across PET(CO(2)) conditions. MSNA burst frequency increased similarly with HUT in all conditions (P < 0.05). However, total MSNA and the increase in total amplitude relative to baseline (%DeltaMSNA) increased more when changing to HUT during Hypo compared with Hyper (P < 0.05). Both BP and Q were higher during Hyper than both Normo and Hypo (main effect; P < 0.05). Therefore, the MSNA response to HUT varied inversely with levels of PET(CO(2)). The combined data suggest that augmented cardiac output with hypercapnia sustained blood pressure during HUT leading to a diminished sympathetic response.

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.

Hypercapnia can induce arousal from sleep in the absence of altered respiratory mechanoreception.

Possible mechanisms of arousal from respiratory stimuli include changes in PO(2), PCO(2), central respiratory drive, or respiratory mechanoreceptor activity. We sought to determine whether hypercapnia alone could induce arousal from sleep in four subjects with high (>/= C3) neurologically complete spinal cord injuries while on constant positive pressure mechanical ventilation (hence, respiratory mechanoreceptor activity remained constant). Subjects were chronically hypocapnic (mean baseline PET(CO(2)) = 21 mm Hg; range, 13-30 mm Hg). On the first night, the baseline rate of spontaneous awakenings was determined by polysomnography. On night two, FI(CO(2)) was increased rapidly in stable NREM sleep. Awakenings occurred in 19 of 19 trials within 5 min, with each subject waking and complaining of shortness of breath (mean time to arousal, 115 s; range, 26-264 s). It is unlikely that these were spontaneous, as the times to awakening during hypercapnia were much higher than during baseline conditions (p < 0.05). During rapidly induced hypercapnia, PET(CO(2)) overestimates the PCO(2) at the central chemoreceptors. To determine more precisely the PET(CO(2)) arousal threshold, PET(CO(2)) was increased slowly (approximately 2 mm Hg/min); arousal occurred at a mean PET(CO(2)) of 37 mm Hg (range, 23-45 mm Hg; mean change from baseline, 15.8 mm Hg, range, 10-20 mm Hg). Hence, both rapid and slow increases in PET(CO(2)) can induce arousal in humans in the absence of changes in respiratory mechanoreceptor activity.

Afferent activity in pulmonary stretch receptors before and after lung injury.

This study was undertaken to determine the effect of a lung-injury on the activity of slowly adapting pulmonary stretch receptors. Comparisons of receptor activity were made at inhibition of inspiratory (phrenic nerve) activity. The inspiratory activity of these receptors was found to be decreased after lung-injury.

Responses of slowly and rapidly adapting receptors in the airways of rabbits to changes in the Starling forces.

1. The responses of the rapidly adapting receptors (RARs) and the slowly adapting receptors (SARs) of the airways to changes in the Starling forces regulating fluid exchange in the pulmonary extravascular space were investigated in anaesthetized rabbits. The hydrostatic pressure in the pulmonary microvasculature was raised by partial obstruction of the mitral valve (mean left atrial pressure increased by approximately 5 and 10 mmHg above the control values) and the concentration of plasma proteins was reduced by plasmapheresis (the total plasma protein concentration reduced by 18%). 2. There was a significant correlation between the action potentials generated by RARs and mean left atrial pressure (n = 12). A similar response was not observed in SARs (n = 12). 3. After plasmapheresis, there was an increase in the resting activity of the RARs (n = 5). In addition, the stimulus-response curve relating mean left atrial pressure and RAR activity was significantly shifted to the left compared to the one elicited before plasmapheresis. Plasmapheresis failed to influence the activity of SARs (n = 5). 4. Obstruction of the pulmonary lymph flow by raising the afterload in the right external jugular vein caused a significant increase in the activity of RARs (n = 6). This response was also maintained during the entire period of lymphatic obstruction. 5. The results show that manipulation of the Starling forces within the lung influences the RAR activity profoundly. It is suggested that the stimulus for the RARs may be a function of the fluid fluxes in the pulmonary extravascular space.

Lung reflexes and receptor activity in a rabbit model of pulmonary fibrosis.

Our objective was to see if activity of individual slowly and rapidly adapting pulmonary receptors was changed by pulmonary fibrosis. Diffuse interstitial lung fibrosis of several weeks' standing was induced in 8 rabbits. They displayed changes in lung mechanics and patterns of breathing, when compared to control rabbits, similar to those seen in patients who develop pulmonary fibrosis. Lung reflexes in the fibrotic rabbits were more profoundly changed than eupneic breathing in a way that could be interpreted as slowly adapting receptor activity, which was increased, being overpowered by a prepotent input from pulmonary rapidly adapting receptors. An increase in number of active rapidly adapting receptors was found in the fibrotic rabbits during direct vagal recording. We have demonstrated that pulmonary receptor activity is changed by lung fibrosis. It may be that these changes in receptor activity produce conflicting respiratory drives that could result in the sensation of dyspnea.

[Regulation of the duration of expiratory phases in decerebrate cats]. / Reguliatsiia dlitel'nosti faz vydokha u detserebrirovannykh koshek.

The changes of durations of the first (postinspiratory, TPIA) and second (TE2) stages of expiration in hypercapnic hyperpnoea before and after bilateral vagotomy and after subsequent injection of pentabarbitone, were evaluated in 10 decerebrated cats. With vagal nerves intact, the hyperpnoea was accompanied by the diminution of the TPIA with no significant changes of the TE2. Vagotomy increased the TPIA. During the hyperpnoea, the TPIA did not change significantly in vagotomized cats whereas the TE2 increased. Pentobarbitone did not affect the TPIA but increased the TE2. Under these conditions, hypercapnia was accompanied by no significant changes of either the TPIA or TE2. The leading part in the regulation of expiratory duration in decerebrated cats seems to be played by the lung mechanoreceptors whose impulses reduce both the TPIA and TE2 in hyperpnoea. The lung stretch receptors impulses inhibit the postinspiratory activity. The TPIA and TE2 regulation is performed by separate central mechanisms. Postinspiratory activity is relatively resistant to pentabarbitone, although the latter delays the start of the next inspiration and obviously suppresses active expirations.

Cardiopulmonary receptor reflex in hypertension.

Several studies have described the modifications of the arterial baroreceptor reflex in hypertension. Whether this condition alters the other major cardiovascular reflex (ie, that originating from receptors in the cardiopulmonary region) is less well known, however. Herein we describe the importance of the inhibitory control of sympathetic vasomotor and renin influences exerted by the cardiopulmonary reflex in normotensive humans as assessed by deactivating and stimulating heart and lung receptors through reductions and increases in central venous pressure respectively obtained via lower-body negative pressure and passive leg raising. Observations on this reflex obtained in experimental animal models are summarized. Finally, we report recent evidence showing that the cardiopulmonary reflex is only slightly affected by mild or moderate essential hypertension but impaired in hypertension with left ventricular hypertrophy in a fashion positively related to the degree of this cardiac structural alteration. This may further worsen the severity of hypertension. However, the impairment of the cardiopulmonary reflex is reversible with regression of hypertrophy obtained by antihypertensive treatment which is thus beneficial for cardiovascular homeostasis.

Effect of vagotomy and thoracic sympathectomy on responses of the monkey to water immersion.

Cardiopulmonary stretch receptors have been implicated as part of a reflex mechanism linking changes in blood volume to changes in renal excretion. Experiments were performed to determine whether total denervation of these receptors by combined cervical vagotomy and thoracic sympathectomy affects the renal responses of the monkey to head-out water immersion, a maneuver that translocates blood to the thorax and elicits an increase in renal salt and water excretion. Macaca fascicularis monkeys first underwent chronic bilateral thoracic sympathectomy or sham denervation performed in two stages a week apart. One to two weeks later, they were anesthetized with pentobarbital sodium, and the sympathectomized animals underwent bilateral cervical vagotomy. Control renal function did not differ between the two groups. Immersion of 90-min duration increased central venous and mean arterial pressures by similar amounts in both groups, but heart rate increased only in the sham-denervated animals. Denervation did not affect the magnitudes or delay the times of onset of the increases in urine flow, absolute and fractional sodium excretion, and osmolar and free water clearances occurring with immersion. These results demonstrate that in the anesthetized monkey cardiopulmonary receptors are not necessary for eliciting the renal responses to immersion.

Effects of hypercapnia on phrenic and stretch receptor responses to lung inflation.

To determine if hypercapnia and reflex bronchoconstriction attenuate lung inflation effects on ventilatory activity by indirect effects on intrapulmonary stretch receptors (PSR), phrenic nerve activity and single unit PSR were monitored at controlled levels of static airway pressure (Paw) and arterial PCO2 in 15 anesthetized dogs. Paw in a vascularly isolated lung was varied between 2 and 14 cm H2O at levels of PaCO2 between 35 and 85 mm Hg. PSR activity (n = 38) in fine strands dissected from an otherwise intact vagus nerve and the integrated phrenic neurogram were recorded. The response to Paw varied from one PSR to another, but was consistent in a given unit; PaCO2 had no consistent effect on individual responses. Selected PSR (n = 15) were averaged to yield a population response to Paw; the selection criteria were: phrenic activity responded briskly to Paw and measurements were made at three levels of PaCO2. Average PSR discharge increased linearly with Paw but was unaffected by PaCO2. On the other hand, phrenic burst frequency decreased as Paw increased and hypercapnia attenuated the slope of this relationship. These results suggest that effects on the relationship between PSR activity and Paw cannot account for attenuation of the relationship between phrenic frequency and Paw in hypercapnia. The effect of PaCO2 on the phrenic frequency vs Paw relationship probably arises from integrative mechanisms in the central nervous system.

Effects of ammonia on lung stretch receptor activity in the rabbit.

The effects of ammonia on lung stretch receptor activity and respiration were studied in the rabbit. This chemical agent caused rapid and shallow breathings or augmented breaths or their combination. The majority of slowly adapting pulmonary stretch receptors (SRs) following ammonia inhalation increased their activity during both inspiration and expiration. At 30 s after ammonia inhalation, the responses of SR activity in both respiratory phases were grouped into four different types: an increase, no effect, a decrease, and no activity. In the time course of ammonia inhalation, the occurrence of a tonic firing pattern of SR activity preceded by a silent phase of the activity was observed in some SRs. In comparison with the findings of a previous report in the rabbit concerning the discharge pattern of SR activity after ammonia inhalation, the results obtained in this study suggest that some SRs in the rabbit are probably located peripheral to the site of the obstruction in the lung unit.