End-inflation Occlusion Method Research Articles

Impaired respiratory mechanics and the role of IL-6 in COPD investigated by end-inflation occlusion method

Impaired respiratory mechanics and the role of IL-6 in COPD investigated by end-inflation occlusion method

P2Y12 Receptor Antagonist Clopidogrel Attenuates Lung Inflammation Triggered by Silica Particles.

Silicosis is an occupational lung disease caused by inhalation of silica particles. It is characterized by intense lung inflammation, with progressive and irreversible fibrosis, leading to impaired lung function. Purinergic signaling modulates silica-induced lung inflammation and fibrosis through P2X7 receptor. In the present study, we investigate the role of P2Y12, the G-protein-coupled subfamily prototype of P2 receptor class in silicosis. To that end, BALB/c mice received an intratracheal injection of PBS or silica particles (20 mg), without or with P2Y12 receptor blockade by clopidogrel (20 mg/kg body weight by gavage every 48 h) – groups CTRL, SIL, and SIL + Clopi, respectively. After 14 days, lung mechanics were determined by the end-inflation occlusion method. Lung histology was analyzed, and lung parenchyma production of nitric oxide and cytokines (IL-1β, IL-6, TNF-α, and TGF-β) were determined. Silica injection reduced animal survival and increased all lung mechanical parameters in relation to CTRL, followed by diffuse lung parenchyma inflammation, increased neutrophil infiltration, collagen deposition and increased pro-inflammatory and pro-fibrogenic cytokine secretion, as well as increased nitrite production. Clopidogrel treatment prevented silica-induced changes in lung function, and significantly reduced lung inflammation, fibrosis, as well as cytokine and nitrite production. These data suggest that inhibition of P2Y12 signaling improves silica-induced lung inflammation, preventing lung functional changes and mortality. Our results corroborate previous observations of silica-induced lung changes and expand the understanding of purinergic signaling in this process.

The effects of nifedipine on respiratory mechanics investigated by theend-inflation occlusion method in the rat

Context: Calcium channel blockers may theoretically exhibit relaxing effects not only on vascular smooth muscle but also on airway smooth muscle.Objective: To investigate possible effects of nifedipine on respiratory mechanics in the rat.Methods: Respiratory system mechanical parameters were measured by the end-inflation occlusion method in the rat in vivo before and after the intraperitoneal administration of nifedipine.Results: We found that nifedipine affects respiratory mechanics, inducing a reduction of airway resistance and of respiratory system elastance, probably because of a relaxing action on airway and parenchimal smooth muscle cells.Conclusion: Should these results be further confirmed by human investigations, a possible role of nifedipine in pharmacological respiratory system’s diseases treatment may be suggested.

The Effects of Prone with Respect to Supine Position on Stress Relaxation, Respiratory Mechanics, and the Work of Breathing Measured by the End-Inflation Occlusion Method in the Rat.

The working hypothesis is that the prone position with respect to supine may change the geometric configuration of the lungs inside the chest wall, thus their reciprocal mechanical interactions, leading to possible effects on stress relaxation phenomena and respiratory mechanics. The effects of changing body posture from supine to prone on respiratory system mechanics, particularly on stress relaxation, were investigated in the rat by the end-inflation occlusion method. In the prone with respect to supine position, an increment of the frictional resistance of the airway (from 0.13 ± 0.01 to 0.19 ± 0.02 cm H2O/l sec(-1), p < 0.05) and a decrement of the stress relaxation-linked pressure dissipation (from 0.51 ± 0.05 to 0.45 ± 0.05 cm H2O/l sec(-1), p < 0.01) were found. Respiratory system elastance and total resistive pressure dissipation did not change significantly. Accordingly, a significant increase of the frictional "ohmic" mechanical inspiratory work of breathing and a decrease of the visco-elastic work of inspiration were demonstrated, while no significant changes occurred for the total mechanical work of breathing and its total resistive and elastic components. It is concluded that postural changes affect the visco-elastic characteristics of the respiratory system and the related stress relaxation phenomena by influencing the disposition and relation of the lungs inside the chest wall and their relative geometrical configuration, and the interaction phenomena of the constitutive parenchymal structures, i.e., elastin and collagen fibers. Since the prone position resulted in no serious or disadvantageous respiratory system mechanical derangement, it is suggested it may be usefully applied in nursing or for therapeutic goals.

A REVIEW OF THE EFFECTS OF BODY TEMPERATURE VARIATIONS ON RESPIRATORY MECHANICS: MEASUREMENTS BY THE END-INFLATION OCCLUSION METHOD IN THE RAT

The temperature of body fluids is expected to affect tissues mechanical properties, including respiratory system tissues. This is because of the changes in airway smooth muscle tone and contractile properties, influencing airway frictional resistance to airflow, and because of the temperature effects on the stress–strain relationships of elastin and collagen, which determinates the elastic behavior of the lungs as reflected by their pressure–volume relationship. Alveolar surfactant biological and physical properties have also been shown to be affected by temperature changes, suggesting influences on the respiratory system hysteretic properties. Experimental works describing the effects of body temperature variations on respiratory mechanics are reviewed, including recent findings dealing with investigations on respiratory mechanics carried out by the end-inflation occlusion method in the rat. This method allows to determine, together with the elastance of the respiratory system, its resistive properties too. In particular, both the ohmic airway resistance due to frictional forces in the airway and the additional visco-elastic resistance exerted because of tissues stress-relaxation may be quantified. The effects of body temperature variations were assessed, and experimentally induced temperature increments and/or decrements allowed to conclude that respiratory system tissues stiffness, both the ohmic and the stress-relaxation linked resistances, and the hysteretic behavior of the respiratory system, decrease with temperature increments. The mechanisms responsible for these effects are analyzed.

P2X7 receptor modulates inflammatory and functional pulmonary changes induced by silica.

Silicosis is an occupational lung disease, characterized by irreversible and progressive fibrosis. Silica exposure leads to intense lung inflammation, reactive oxygen production, and extracellular ATP (eATP) release by macrophages. The P2X7 purinergic receptor is thought to be an important immunomodulator that responds to eATP in sites of inflammation and tissue damage. The present study investigates the role of P2X7 receptor in a murine model of silicosis. To that end wild-type (C57BL/6) and P2X7 receptor knockout mice received intratracheal injection of saline or silica particles. After 14 days, changes in lung mechanics were determined by the end-inflation occlusion method. Bronchoalveolar lavage and flow cytometry analyzes were performed. Lungs were harvested for histological and immunochemistry analysis of fibers content, inflammatory infiltration, apoptosis, as well as cytokine and oxidative stress expression. Silica particle effects on lung alveolar macrophages and fibroblasts were also evaluated in cell line cultures. Phagocytosis assay was performed in peritoneal macrophages. Silica exposure increased lung mechanical parameters in wild-type but not in P2X7 knockout mice. Inflammatory cell infiltration and collagen deposition in lung parenchyma, apoptosis, TGF-β and NF-κB activation, as well as nitric oxide, reactive oxygen species (ROS) and IL-1β secretion were higher in wild-type than knockout silica-exposed mice. In vitro studies suggested that P2X7 receptor participates in silica particle phagocytosis, IL-1β secretion, as well as reactive oxygen species and nitric oxide production. In conclusion, our data showed a significant role for P2X7 receptor in silica-induced lung changes, modulating lung inflammatory, fibrotic, and functional changes.

Hyperbaric Air Exposure at 2.5 ATA Does Not Affect Respiratory Mechanics and Lung Histology in the Rat

We previously demonstrated that the exposure to hyperbaric hyperoxia increased respiratory system elastance and both the "ohmic" and viscoelastic components of inspiratory resistances, probably because of increased oxygen tension toxic effects. We presently investigated the possible consequences of a single exposure to 2.5-atmospheres absolute air (hyperbarism) lasting 90 min. We used the end-inflation occlusion method on anesthetized rats after about 15 min from previous exposure to hyperbarism. The method allows the measurements of respiratory system elastance and of the ohmic and viscoelastic components of airway resistance, which respectively depend on the Newtonian pressure dissipation due to the ohmic airway resistance to airflow and on the viscoelastic pressure dissipation caused by respiratory system tissue stress relaxation. The expressions of inducible NO synthase (iNOS) and endothelial NO synthase (eNOS) in the lung's tissues were also investigated, together with the histological characteristics of lung tissue. Data were compared with those obtained in control animals and in previously studied animals exposed to hyperoxic hyperbarism. Unlike with hyperoxic hyperbarism, hyperbarism per se did not change significantly the parameters of respiratory mechanics in the control animals (respiratory system elastance and ohmic and viscoelastic resistances were 2.01 ± 0.17 vs. 1.74 ± 0.08 cm H(2)O/ml, and 0.13 ± 0.02 vs. 0.13 ± 0.03 and 0.425 ± 0.04 vs. 0.33 ± 0.03 cm H(2)O/ml s(-1) in control vs. experimental animals, respectively, none significantly different), nor did it induce evident effects on lung histology. An increment of both iNOS and eNOS expressions was documented instead (0.50 ± 0.05 vs. 0.75 ± 0.07 and 1.04 ± 0.1 and 1.4 ± 0.15, respectively). Our results indicate that, at variance with hyperoxic hyperbarism, the acute exposure to only hyperbarism does not affect either the elastic or the resistive respiratory system properties, or lung histology.

The volume dependence of stress relaxation in the rat respiratory system

ABSTRACTAim: To investigate the volume dependence of respiratory system stress relaxation in anesthetized, positive-pressure ventilated rats. Materials and methods: The effects on respiratory system stress relaxation of changing the end inflation volume while keeping tidal volume constant, and of changing the tidal volume while maintaining constant end inflation volume, were separately studied by the end-inflation occlusion method. These changes were obtained by inflating the respiratory system starting from different volumes above functional residual capacity. Results: We found that: (1) a simple exponential equation well describe the visco-elastic pressure drop for different inflation modalities; (2) the stress relaxation-linked, visco-elastic pressure drop, increases with increasing the tidal volume and keeping the end-inflation volume constant, but is independent from the end-inflation lung volume at constant tidal volumes; (3) time constant values show a significant increment with end-inflation volume at constant tidal volume but result independent from tidal volume variation at constant end-inflation volume. Conclusions: Stress relaxation-linked pressure dissipation increases with increasing tidal volume independently from end-inspiratory volume.

Interleukin-6 and Lung Inflammation: Evidence for a Causative Role in Inducing Respiratory System Resistance Increments

Interleukin-6 is a multifunctional cytokine that has been shown to be increased in some pathological conditions involving the respiratory system such as those experimentally induced in animals or spontaneously occurring in humans. Experimental data demonstrating that interleukin-6 plays a significant role in commonly occurring respiratory system inflammatory diseases are reviewed here. Those diseases, i.e. asthma and chronic obstructive pulmonary disease, are characterised by mechanical derangements of the respiratory system, for the most part due to increased elastance and airway resistance. Recent findings showing that interleukin-6 has a causative role in determining an increase in airway resistance are reviewed. The end-inflation occlusion method was used to study the mechanical properties of the respiratory system before and after interleukin-6 administration. The cytokine was shown to induce significant, dose-dependent increments in both the resistive pressure dissipation due to frictional forces opposing the airflow in the airway (ohmic resistance) and the additional resistive pressure dissipation due to the visco-elastic properties of the system, i.e. stress relaxation (visco-elastic resistance). There were no alterations in respiratory system elastance. Even when administered to healthy mammals, interleukin-6 determines a significant effect on respiratory system resistance causing an increase in the mechanical work of breathing during inspiration. IL-6 hypothetically plays an active role in the pathogenesis of respiratory system diseases and the mechanisms that may be involved are discussed here.

The Effect of Acute Exposure to Hyperbaric Oxygen on Respiratory System Mechanics in the Rat

This study was designed to investigate the possible effects of acute hyperbaric hyperoxia on respiratory mechanics of anaesthetised, positive-pressure ventilated rats. We measured respiratory mechanics by the end-inflation occlusion method in nine rats previously acutely exposed to hyperbaric hyperoxia in a standard fashion. The method allows the measurements of respiratory system elastance and of both the "ohmic" and of the viscoelastic components of airway resistance, which respectively depend on the newtonian pressure dissipation due to the ohmic airway resistance to air flow, and on the viscoelastic pressure dissipation caused by respiratory system tissues stress-relaxation. The activities of inducible and endothelial NO-synthase in the lung's tissues (iNOS and eNOS respectively) also were investigated. Data were compared with those obtained in control animals. We found that the exposure to hyperbaric hyperoxia increased respiratory system elastance and both the "ohmic" and viscoelastic components of inspiratory resistances. These changes were accompanied by increased iNOS but not eNOS activities. Hyperbaric hyperoxia was shown to acutely induce detrimental effects on respiratory mechanics. A possible causative role was suggested for increased nitrogen reactive species production because of increased iNOS activity.

The effect of body cooling on respiratory system mechanics and hysteresis in rats

Literature reports and theoretical considerations suggest that body cooling may affect respiratory mechanics in vivo. To examine this hypothesis, healthy rats were studied using the end-inflation occlusion method under control conditions and after total body cooling. Respiratory mechanics parameters, hysteresis areas, the inspiratory work of breathing, and its elastic and resistive components, were calculated. After body cooling (mean rectal temperature from 36.6±0.25 to 32.1±0.26°C), the ohmic and the additional visco-elastic respiratory system resistances, the hysteresis, the total inspiratory work of breathing, and its resistive components, were all increased. No significant changes were detected for the static and dynamic respiratory system elastance mean values, and the related elastic component of the work of breathing. These data indicate that body cooling increases the mechanical inspiratory work of breathing by increasing the resistive pressures dissipation. This effect is evident even for limited temperature variations, and it is suggested that it may occur in the event of accidental or therapeutic hypothermia.

The Effects of Erythropoietin on the Respiratory Function: Measurements of Respiratory Mechanics in the Rat

Data reported in the literature indicate that erythropoietin (EPO) influences mammals respiratory function, for example stimulating pulmonary ventilation. Direct experimentations about possible effects of EPO on respiratory mechanics are lacking. In the present report, the endinflation occlusion method was applied in control and EPO-treated anaesthetised and positive-pressure ventilated rats to assess respiratory mechanics. The method involves a sudden flow arrest after a constant flow inflation, and allows to measure the ohmic airway resistance and the respiratory system elastance. A significant decrement of the ohmic airway resistance after 20 and 30 minutes from i.p. EPO administration was observed in experimental animals, which was not seen in control animals. The elastic characteristics of the respiratory system did not change over time in both groups. Hypothesis about the mechanism(s) explaining the results and potential applications to humans are addressed. In particular, further data were obtained by performing additional experiments suggesting that the observed airway resistance decrement may be related to an EPO-induced increased nitric oxide production, a rather well known bronchodilator agent. Literature and present results indicate that the spontaneous increments of plasmatic EPO concentrations, such as those happening in hypoxia and/or blood loss, may be associated with airway resistance decrement. It is suggested that erythropoietin, beside the well known effect on haematopoiesis, may activate complex physiological responses including haematological, circulatory and respiratory adaptations to hypoxia in mammals. Keywords: Airway resistance, end-inflation occlusion method, erythropoietin, hypoxia, rat, respiratory mechanics.

Regular exercise training attenuates pulmonary inflammatory responses to inhaled alumina refinery dust in mice

Exposure to alumina dust has been recently associated with impaired lung mechanics and inflammation. We aimed at evaluating if moderate exercise training prevents these outcomes. Twenty-three female BALB/c mice (25–30g) were randomly divided in two main groups: control (C) and exercise (E), which were submitted, or not, to 15min of swimming, 5 days/week during 4 weeks. Then, the animals were exposed for 1h to either saline solution (CS or ES) or to a suspension of 8mg/m3 of alumina dust (CA or EA). Twenty-four hours later pulmonary mechanics was determined by the end-inflation occlusion method. Left lungs were prepared for histology and right lungs for TGF-β determination. Static elastance increased after alumina dust exposure independently of swimming. In CA group the viscoelastic component of elastance, the viscoelastic/inhomogeneous pressure, the polymorphonuclear amount, the fraction area of alveolar collapse and TGF-β increased. Thus, exercise training may mitigate the pro-inflammatory response to inhaled aluminum refinery dust.

The Effects of Erythropoietin on the Respiratory Function: Measurements of Respiratory Mechanics in the Rat

Data reported in the literature indicate that erythropoietin (EPO) influences mammals respiratory function, for example stimulating pulmonary ventilation. Direct experimentations about possible effects of EPO on respiratory mechanics are lacking. In the present report, the endinflation occlusion method was applied in control and EPO-treated anaesthetised and positive-pressure ventilated rats to assess respiratory mechanics. The method involves a sudden flow arrest after a constant flow inflation, and allows to measure the ohmic airway resistance and the respiratory system elastance. A significant decrement of the ohmic airway resistance after 20 and 30 minutes from i.p. EPO administration was observed in experimental animals, which was not seen in control animals. The elastic characteristics of the respiratory system did not change over time in both groups. Hypothesis about the mechanism(s) explaining the results and potential applications to humans are addressed. In particular, further data were obtained by performing additional experiments suggesting that the observed airway resistance decrement may be related to an EPO-induced increased nitric oxide production, a rather well known bronchodilator agent. Literature and present results indicate that the spontaneous increments of plasmatic EPO concentrations, such as those happening in hypoxia and/or blood loss, may be associated with airway resistance decrement. It is suggested that erythropoietin, beside the well known effect on haematopoiesis, may activate complex physiological responses including haematological, circulatory and respiratory adaptations to hypoxia in mammals.

Erythropoietin acutely decreases airway resistance in the rat

While some experimental data suggest that erythropoietin (EPO) influences respiratory mechanics, reports on scientific trials are lacking.In the present work, respiratory mechanics were measured using the end-inflation occlusion method in control and EPO treated anaesthetised and positive-pressure ventilated rats. Causing an abrupt inspiratory flow arrest, the end-inflation occlusion method makes it possible to measure the ohmic airway resistance and the respiratory system elastance.It was found that EPO induces a significant decrement in the ohmic airway resistance, not noted in control animals, 20 and 30min after intraperitoneal EPO injection. The elastic characteristics of the respiratory system did not vary.Hypotheses about the mechanism (s) explaining these results were addressed. In particular, additional experiments have indicated that the decrement in airway resistance could be related to an increase in nitric oxide production induced by EPO.Spontaneous increments in plasmatic erythropoietin levels, such as those that take place in association with hypoxia and/or blood loss, appear to be related to the decrement in airway resistance, allowing pulmonary ventilation to increase without altering respiratory mechanics leading to deleterious increments in energy dissipation during breathing.

The effect of angiotensin-converting enzyme inhibition by captopril on respiratory mechanics in healthy rats

Context: Angiotensin stimulates smooth-muscle contraction. Accordingly, angiotensin-converting enzyme (ACE) inhibition is expected to decrease airway resistance.Objectives: To measure the effects of ACE inhibition on respiratory mechanics in healthy mammals.Materials and methods: We measured respiratory mechanics before and after i.p. ACE inhibitor captopril (100 mg/kg) in normal anaesthetised rats. The end-inflation occlusion method allowed the measurements of respiratory system elastance and ohmic and viscoelastic pressure dissipations. Respiratory system hysteresis and the elastic and resistive work of breathing were calculated.Results: Captopril induced a reduction of the ohmic and the total respiratory system resistances, while respiratory system hysteresis and elastance did not change. Accordingly, a reduction of the resistive and of the total work of breathing was observed.Conclusions: The captopril-induced reduction of airway resistance indicates that angiotensin modulates bronchomotor tone in basal conditions. ACE inhibition may positively affect respiratory system mechanics and work of breathing.

Effects of the pneumoperitoneum and Trendelenburg position on respiratory mechanics in the rats by the end-inflation occlusion method

PURPOSE:To describe the consequences of the cranial displacement of the diaphgram occurring during pneumoperitoneum (Pnp) and/or Trendelenburg (Tnd) position on respiratory mechanics. Possible addictive effects and the changes of the viscoelastic respiratory system resistance were studied, which were not extensively described before.METHODS:The end-inflation occlusion method was applied on eight rats. It allows us to determine mechanical parameters such as respiratory system static elastance, the ohmic resistance due to frictional forces in the airways, and the additional viscoelastic impedance due to tissues deformation. Measurements during mechanical ventilation were taken in controls (supine position), after 20–25° head-down tilting (Tnd), after abdominal air insufflation up to 12 mmHg abdominal pressure in the supine position (Pnp), and combining Tnd + Pnp. Tnd and Pnp modalities were similar to those commonly applied during surgical procedures in humans.RESULTS:We confirmed the previously described detrimental effects on respiratory mechanics due to the diaphgram displacement during both Pnp and Tnd. The increment in the total resistive pressure dissipation was found to depend primarily on the effects on the viscoelastic characteristics of the respiratory system. Data suggesting greater effects of Pnp compared to those of Tnd were obtained.CONCLUSION:The cranial displacement of the diaphgram occurring as a consequence of Pnp and/or Tnd, for example during laparoscopic surgical procedures, causes an increment of respiratory system elastance and viscoelastic resistance. The analysis of addictive effects show that these are more likely to occur when Pnp + Tnd are compared to isolated Tnd rather than to isolated Pnp.

Lipopolysaccharide-induced lung injury: Role of P2X7 receptor

P2X7 receptors have been involved in inflammatory and immunological responses, and their activation modulates pro-inflammatory cytokines production by LPS-challenged macrophages. To determine the role of P2X7R in LPS-induced acute lung injury in mice. Wild-type (C57BL/6) and P2X7 knockout mice received intratracheal injection of saline or Escherichia coli LPS (60 μg). After 24h, changes in lung mechanics were determined by the end-inflation occlusion method. Bronchoalveolar lavage was performed, and lungs were harvested for measurement of morphometry, fibers content, inflammatory cells and cytokine expression by histochemistry and immunohistochemistry. Compared with saline, LPS increased lung mechanical parameters, mast cell, collagen and fibronectin deposition in lung parenchyma, as well as nitric oxide and lactate dehydrogenase release into bronchoalveolar fluid in wild-type, but not in P2X7R knockout mice. Alveolar collapse, lung influx of polymorphonuclear and CD14(+) cells, as well as TGF-β, MMP-2, and IL-1β release were higher in wild-type than knockout LPS-challenged mice, while MMP-9 release where similar between the two genotypes. LPS increased macrophage immunoreactivity in lung tissue in both genotypes, but macrophages were not activated in the P2X7R knockout mice. Furthermore, LPS administration increased P2X7R immunoexpression in lung parenchyma in wild-type mice, and TLR4 in both wild-type and P2X7R knockout mice. P2X7 receptors are implicated in the pathophysiology of LPS-induced lung injury, modulating lung inflammatory and functional changes.

Effects of cysteinyl-leukotriene receptors’ antagonism by montelukast on lung mechanics and olfactory system histology in healthy mice

Context: At variance with steroid administration, the possible effects of leukotrienes inhibition on basal respiratory mechanics and olfactory system function are still unclear.Objective: To investigate if interference with the leukotrienes activity may influence basal lung mechanics in healthy mammals, as well as the olfactory system.Materials and methods: We measured lung mechanics by the end-inflation occlusion method in control and in montelukast i.p. treated anaesthetised healthy mice (10 mg/kg/die for a week). A study of olfactory system histology was also conducted.Results: Elastance and resistive properties of the lung were not affected by montelukast, while a significant increment of lung hysteresis was observed. The analysis of olfactory system histology revealed no significant effects of montelukast compared to controls.Discussion and conclusions: Leukotrienes’ antagonism does not affect respiratory mechanics in basal conditions, except for a hysteresis increment, which might counteract the increase in expiratory flow in asthmatic subjects assuming montelukast.

The Effect of NG-Nitro-L-Arginine Methyl Ester, a Nitric Oxide Synthase Inhibitor, on Respiratory Mechanics in Rats

Background: Data describing the inhibitory effects of nitric oxide synthase (NOS) on respiratory mechanics are conflicting, and no data are available concerning possible effects on the viscoelasticity of the respiratory system, on the inspiratory work of breathing (WOB) or on respiratory system hysteresis. Objectives: The aim of this study was to measure the effects of NOS inhibition by N^G-nitro-L-arginine methyl ester (L-NAME) on respiratory mechanics in normal anesthetized rats. Methods: Using the end-inflation occlusion method, it was possible to quantify the ohmic and viscoelastic airway resistance and elastance of the respiratory system. Ohmic resistance is the normalized-to-flow pressure dissipation due to viscous forces opposing the airflow in the airways, as predicted by the Poiseuille law. Viscoelastic resistance is the normalized-to-flow pressure dissipation due to the resistance of respiratory system tissue to deformation during inflation, which is recovered after the arrest of the inspiratory flow (stress relaxation). The inspiratory WOB, its elastic and resistive components, and hysteresis were also calculated. Results:L-NAME induced an increment in the ohmic airway resistance and in the resistive ohmic inspiratory WOB. The viscoelastic resistance due to stress relaxation and the elastic properties of the respiratory system were not modified, and no effect was detected on the related components of the inspiratory WOB and on hysteresis. Conclusions: NO acts in normal rats to reduce the ohmic component of airway resistance, decreasing the ohmic inspiratory WOB. The elastic and viscoelastic components are unaltered. Hysteresis is also unaltered, suggesting that NO has negligible effects on alveolar surfactant activity.