Hypercapnic ventilatory responses in mice differentially susceptible to acute ozone exposure

1993 ◽  
Vol 75 (6) ◽  
pp. 2613-2619 ◽  
Author(s):  
C. G. Tankersley ◽  
R. S. Fitzgerald ◽  
W. A. Mitzner ◽  
S. R. Kleeberger
Keyword(s):  
Minute Ventilation ◽  
Pulmonary Inflammation ◽  
Inbred Strains ◽  
Ozone Exposure ◽  
Whole Body ◽  
Ventilatory Control ◽  
Air Exposure ◽  
Ventilatory Responses ◽  
Inbred Strains Of Mice ◽  
Induced Changes

Susceptibility to ozone (O3)-induced pulmonary inflammation is greater in C57BL/6J (B6) than in C3H/HeJ (C3) strain of mice. We tested the hypothesis that altered ventilatory control occurs in B6 mice to a greater extent than in C3 mice after acute O3 exposure. Age-, sex-, and weight-matched C3 and B6 mice were exposed for 3 h to either 2 ppm O3 or filtered air. One and 24 h after O3 or air exposure, whole body plethysmography was used to measure breathing frequency (f), tidal volume (VT), and minute ventilation (VE). To assess changes in ventilatory control, mice were challenged by the elevation of fractional concentration of inspired CO2 levels to 5 and 8% in air for 10 min. After air exposure, there were significantly (P < 0.01) greater changes in VE in B6 than in C3 mice. Hypercapnia-induced changes in VE were significantly (P < 0.01) attenuated in B6 mice 1 h after O3 exposure. VT was significantly (P < 0.01) reduced 1 h after O3 in B6 and C3 mice; however, C3 mice increased f to sustain the hypercapnic VE response similar to air exposure. In contrast, the diminished VT in B6 mice 1 h after O3 occurred coincident with significantly (P < 0.01) reduced f, mean inspiratory flow, and slope of VE-to-%CO2 relationship compared with air exposure. Altered hypercapnic VE in B6 mice was partially reversed 24 h after O3 relative to air-exposed levels. These data suggest that control of ventilation during phenotypic response to CO2 is governed, in part, by genetic factors in inbred strains of mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential control of ventilation among inbred strains of mice

1994 ◽  
Vol 267 (5) ◽  
pp. R1371-R1377 ◽  
Author(s):  
C. G. Tankersley ◽  
R. S. Fitzgerald ◽  
S. R. Kleeberger
Keyword(s):  
Minute Ventilation ◽  
Inbred Strains ◽  
Whole Body ◽  
Genetic Determinants ◽  
Ventilatory Responses ◽  
Hypoxic Conditions ◽  
Inbred Strains Of Mice ◽  
Genetic Mechanisms ◽  
The Difference ◽  
Differential Control

The role genetic factors play in ventilatory control was examined by challenging eight inbred strains of mice to acute hypercapnia under normoxic and hypoxic conditions. Age-matched mice were exposed for 3-5 min to inspired gases of the following composition (FICO2:FIO2) 0.03:0.10, 2) 0.03:0.21, 3) 0.08:0.10, and 4) 0.08:0.21, with intermittent room air exposures. Breathing frequency (f) and tidal volume (VT) of unanesthetized, unrestrained mice were assessed by whole body plethysmography. During room air breathing, significant (P < 0.01) interstrain differences were noted in the pattern, but minute ventilation (VE) did not differ among the strains. Relative to room air, mild hypercapnia with hypoxia (0.03:0.10) significantly (P < 0.01) elevated VE in each strain, and the percent increase in VE of the DBA/2J strain was significantly (P < 0.05) greater than the other strains. The ventilatory response to these conditions was achieved primarily by a significant (P < 0.01) increase in f among the strains. During severely hypercapnic normoxia (0.08:0.21) and hypoxia (0.08:0.10), the increase in VE was significantly (P < 0.01) greatest in the C57BL/6J (B6) mice and least in the C3H/HeJ (C3) mice. The difference in hypercapnic VE between B6 and C3 strains was largely due to a significantly (P < 0.01) greater increase in VT by B6 mice. On the assumption that environmental factors were identical, these data suggest that genetic determinants govern interstrain variation in the magnitude and pattern of breathing during hypoxia and hypercapnia. Moreover, hypoxic and hypercapnic ventilatory responses appear to be influenced by different genetic mechanisms.

Ventilatory behavior after hypoxia in C57BL/6J and A/J mice

2001 ◽  
Vol 91 (5) ◽  
pp. 1962-1970 ◽  
Author(s):  
Fang Han ◽  
Shyam Subramanian ◽  
Thomas E. Dick ◽  
Ismail A. Dreshaj ◽  
Kingman P. Strohl
Keyword(s):  
Airway Resistance ◽  
Minute Ventilation ◽  
Genetic Effect ◽  
Strain Differences ◽  
Whole Body ◽  
Environmental Forcing ◽  
Ventilatory Responses ◽  
Term Potentiation ◽  
Genetic Mechanisms ◽  
Whole Body Plethysmography

Given the environmental forcing by extremes in hypoxia-reoxygenation, there might be no genetic effect on posthypoxic short-term potentiation of ventilation. Minute ventilation (V˙e), respiratory frequency (f), tidal volume (Vt), and the airway resistance during chemical loading were assessed in unanesthetized unrestrained C57BL/6J (B6) and A/J mice using whole body plethysmography. Static pressure-volume curves were also performed. In 12 males for each strain, after 5 min of 8% O2 exposure, B6 mice had a prominent decrease inV˙e on reoxygenation with either air (−11%) or 100% O2 (−20%), due to the decline of f. In contrast, A/J animals had no ventilatory undershoot or f decline. After 5 min of 3% CO2-10% O2 exposure, B6 exhibited significant decrease in V˙e (−28.4 vs. −38.7%, air vs. 100% O2) and f (−13.8 vs. −22.3%, air vs. 100% O2) during reoxygenation with both air and 100% O2; however, A/J mice showed significant increase inV˙e (+116%) and f (+62.2%) during air reoxygenation and significant increase in V˙e (+68.2%) during 100% O2 reoxygenation. There were no strain differences in dynamic airway resistance during gas challenges or in steady-state total respiratory compliance measured postmortem. Strain differences in ventilatory responses to reoxygenation indicate that genetic mechanisms strongly influence posthypoxic ventilatory behavior.

Effects of acute and chronic acetazolamide on resting ventilation and ventilatory responses in men

1993 ◽  
Vol 74 (1) ◽  
pp. 230-237 ◽  
Author(s):  
E. R. Swenson ◽  
J. M. Hughes
Keyword(s):  
Metabolic Acidosis ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Respiratory Acidosis ◽  
Acute Effects ◽  
Acid Base Balance ◽  
Ventilatory Control ◽  
Peripheral Chemoreceptor ◽  
Ventilatory Responses ◽  
Base Balance

The effects of acetazolamide (ACTZ) on ventilatory control are thought to be mediated by metabolic acidosis. However, carbonic anhydrase (CA) inhibition within brain and chemoreceptors and tissue respiratory acidosis may also be important. We compared the acute effects of ACTZ (tissue respiratory acidosis and tissue CA inhibition without metabolic acidosis) on ventilation and ventilatory control with chronic ACTZ (acute effects plus metabolic acidosis). Five men were studied 1 h after 500 mg iv ACTZ or 0.9% saline (acute effects) and also after three doses of ACTZ (500 mg po every 6 h; chronic effects). Minute ventilation (VE), steady-state hypercapnic ventilatory response (HCVR), and hypoxic ventilatory response (HVR) were measured with respiratory inductance plethysmography. Resting VE was increased equally by acute and chronic ACTZ. HCVR increased with chronic ACTZ in hyperoxia and even further in hypoxia. In contrast, acute ACTZ had no effect on the HCVR slope in hyperoxia and suppressed its augmentation by hypoxia. HVR was fully suppressed by acute ACTZ but unchanged with chronic ACTZ. ACTZ also slowed the rate of full ventilatory response to CO2. These findings show that CA inhibitors affect ventilatory control in a complex fashion, not only through changes in systemic acid-base balance but also by central and peripheral chemoreceptor inhibition.

The affinity of hemoglobin for oxygen affects ventilatory responses in mutant mice with Presbyterian hemoglobinopathy

2003 ◽  
Vol 285 (4) ◽  
pp. R747-R753 ◽  
Author(s):  
Masahiko Izumizaki ◽  
Masakatsu Tamaki ◽  
Yo-ichi Suzuki ◽  
Michiko Iwase ◽  
Takuji Shirasawa ◽  
...  
Keyword(s):  
Minute Ventilation ◽  
Globin Gene ◽  
Open Circuit ◽  
Mutant Mice ◽  
Whole Body ◽  
Wild Type ◽  
Peripheral Tissues ◽  
Ventilatory Responses ◽  
Significant Difference ◽  
In The Wild

The purpose of this study was to test whether chronically enhanced O2 delivery to tissues, without arterial hyperoxia, can change acute ventilatory responses to hypercapnia and hypoxia. The effects of decreased hemoglobin (Hb)-O2 affinity on ventilatory responses during hypercapnia (0, 5, 7, and 9% CO2 in O2) and hypoxia (10 and 15% O2 in N2) were assessed in mutant mice expressing Hb Presbyterian (mutation in the β-globin gene, β108 Asn → Lys). O2 consumption during normoxia, measured via open-circuit methods, was significantly higher in the mutant mice than in wild-type mice. Respiratory measurements were conducted with a whole body, unrestrained, single-chamber plethysmograph under conscious conditions. During hypercapnia, there was no difference between the slopes of the hypercapnic ventilatory responses, whereas minute ventilation at the same levels of arterial PCO2 was lower in the Presbyterian mice than in the wild-type mice. During both hypoxic exposures, ventilatory responses were blunted in the mutant mice compared with responses in the wild-type mice. The effects of brief hyperoxia exposure (100% O2) after 10% hypoxia on ventilation were examined in anesthetized, spontaneously breathing mice with a double-chamber plethysmograph. No significant difference was found in ventilatory responses to brief hypoxia between both groups of mice, indicating possible involvement of central mechanisms in blunted ventilatory responses to hypoxia in Presbyterian mice. We conclude that chronically enhanced O2 delivery to peripheral tissues can reduce ventilation during acute hypercapnic and hypoxic exposures.

scholarly journals Pulmonary responses to acute ozone exposure in fasted mice: effect of leptin administration

2007 ◽  
Vol 102 (1) ◽  
pp. 149-156 ◽  
Author(s):  
Richard A. Johnston ◽  
Todd A. Theman ◽  
Raya D. Terry ◽  
Erin S. Williams ◽  
Stephanie A. Shore
Keyword(s):  
Bronchoalveolar Lavage ◽  
Continuous Infusion ◽  
Pulmonary Inflammation ◽  
Airway Responsiveness ◽  
Ozone Exposure ◽  
Pulmonary Mechanics ◽  
Serum Leptin ◽  
Mechanistic Basis ◽  
Inflammatory Profile ◽  
Induced Changes

Leptin is a satiety hormone that also has proinflammatory effects, including augmentation of ozone-induced pulmonary inflammation. The purpose of this study was to determine whether reductions in endogenous levels of leptin can attenuate pulmonary responses to ozone. To reduce serum leptin, we fasted mice overnight before ozone exposure. Fasting caused a marked reduction in serum leptin to approximately one-sixth the levels observed in fed mice, and continuous infusion of leptin via Alzet micro-osmotic pumps restored serum leptin to, but not above, fed levels. Ozone exposure (2 ppm for 3 h) caused a significant, ∼40% increase in pulmonary resistance ( P < 0.01) and increased airway responsiveness in fasted but not in fed mice. The increased effect of ozone on pulmonary mechanics and airway responsiveness in fasted mice was not observed when leptin was restored via continuous infusion. Ozone exposure caused pulmonary inflammation, as evident by increases in bronchoalveolar lavage cells, protein, and soluble tumor necrosis factor receptors. There was no effect of fasting status on ozone-induced changes in the bronchoalveolar lavage inflammatory profile, and leptin treatment did not alter these responses. Our results indicate that fasting augments ozone-induced changes in pulmonary mechanics and airway responsiveness in mice. These effects of fasting are the result of declines in serum leptin. The mechanistic basis for this protective effect of leptin in fasted mice remains to be determined but is not related to effects on ozone-induced inflammation.

scholarly journals Ventilatory responses to ozone are reduced in immature rats

2000 ◽  
Vol 88 (6) ◽  
pp. 2023-2030 ◽  
Author(s):  
S. A. Shore ◽  
J. H. Abraham ◽  
I. N. Schwartzman ◽  
G. G. Krishna Murthy ◽  
J. D. Laporte
Keyword(s):  
Bronchoalveolar Lavage ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Ventilatory Responses ◽  
Sprague Dawley Rats ◽  
Immature Rats ◽  
Old Rats ◽  
Induced Changes

During ozone (O3) exposure, adult rats decrease their minute ventilation (V˙e). To determine whether such changes are also observed in immature animals, Sprague-Dawley rats, aged 2, 4, 6, 8, or 12 wk, were exposed to O3(2 ppm) in nose-only-exposure plethysmographs. BaselineV˙e normalized for body weight decreased with age from 2.1 ± 0.1 ml ⋅ min−1⋅ g−1in 2-wk-old rats to 0.72 ± 0.03 ml ⋅ min−1⋅ g−1in 12-wk-old rats, consistent with the higher metabolic rates of younger animals. In adult (8- and 12-wk-old) rats, O3caused 40–50% decreases in V˙e that occurred primarily as the result of a decrease in tidal volume. In 6-wk-old rats, O3-induced changes inV˙e were significantly less, and in 2- and 4-wk-old rats, no significant changes inV˙e were observed during O3exposure. The increased baseline V˙e and the smaller decrements in V˙e induced by O3in the immature rats imply that their delivered dose of O3is much higher than in adult rats. To determine whether these differences in O3dose influence the extent of injury, we measured bronchoalveolar lavage protein concentrations. The magnitude of the changes in bronchoalveolar lavage induced by O3was significantly greater in 2- than in 8-wk-old rats (267 ± 47 vs. 165 ± 22%, respectively, P < 0.05). O3exposure also caused a significant increase in PGE2in 2-wk-old but not in adult rats. The results indicate that the ventilatory response to O3is absent in 2-wk-old rats and that lack of this response, in conjunction with a greater specific ventilation, leads to greater lung injury.

Ozone-induced changes in pulmonary function and bronchial responsiveness in asthmatics

1989 ◽  
Vol 66 (1) ◽  
pp. 217-222 ◽  
Author(s):  
J. W. Kreit ◽  
K. B. Gross ◽  
T. B. Moore ◽  
T. J. Lorenzen ◽  
J. D'Arcy ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Minute Ventilation ◽  
Normal Subjects ◽  
Cycle Ergometer ◽  
Ozone Exposure ◽  
Bronchial Responsiveness ◽  
Before And After ◽  
Effective Doses ◽  
Induced Changes ◽  
Percent Decrease

To compare the responses of asthmatic and normal subjects to high effective doses of ozone, nine asthmatic and nine normal subjects underwent two randomly assigned 2-h exposures to filtered, purified air and 0.4 ppm ozone with alternating 15-min periods of rest and exercise on a cycle ergometer (minute ventilation = 30 l.min-1.m-2). Before and after each exposure, pulmonary function and bronchial responsiveness to methacholine were measured and symptoms were recorded. Ozone exposure was associated with a statistically significant decrease in forced vital capacity (FVC), forced expired volume in 1 s (FEV1), percent FEV1 (FEV1%), and forced expired flow at 25–75% FVC (FEF25–75) in both normal and asthmatic subjects. However, comparing the response of asthmatic and normal subjects to ozone revealed a significantly greater percent decrease in FEV1, FEV1%, and FEF25–75 in the asthmatic subjects. The effect of ozone on FVC and symptom scores did not differ between the two groups. In both normal and asthmatic subjects, exposure to ozone was accompanied by a significant increase in bronchial responsiveness. We conclude that exposure to a high effective ozone dose produces 1) increased bronchial responsiveness in both normal and asthmatic subjects, 2) greater airways obstruction in asthmatic than in normal subjects, and 3) similar symptoms and changes in lung volumes in the two groups.

scholarly journals The Role of Carotid Sinus Nerve Input in the Hypoxic-Hypercapnic Ventilatory Response in Juvenile Rats

2020 ◽  
Vol 11 ◽  
Author(s):  
Paulina M. Getsy ◽  
Gregory A. Coffee ◽  
Stephen J. Lewis
Keyword(s):  
Carotid Sinus ◽  
Nucleus Tractus Solitarius ◽  
Minute Ventilation ◽  
Respiratory Pattern ◽  
Whole Body ◽  
Carotid Sinus Nerve ◽  
Sprague Dawley ◽  
Juvenile Rats ◽  
Ventilatory Responses ◽  
Chemosensory Pathway

In juvenile rats, the carotid body (CB) is the primary sensor of oxygen (O2) and a secondary sensor of carbon dioxide (CO2) in the blood. The CB communicates to the respiratory pattern generator via the carotid sinus nerve, which terminates within the commissural nucleus tractus solitarius (cNTS). While this is not the only peripheral chemosensory pathway in juvenile rodents, we hypothesize that it has a unique role in determining the interaction between O2 and CO2, and consequently, the response to hypoxic-hypercapnic gas challenges. The objectives of this study were to determine (1) the ventilatory responses to a poikilocapnic hypoxic (HX) gas challenge, a hypercapnic (HC) gas challenge or a hypoxic-hypercapnic (HH) gas challenge in juvenile rats; and (2) the roles of CSN chemoafferents in the interactions between HX and HC signaling in these rats. Studies were performed on conscious, freely moving juvenile (P25) male Sprague Dawley rats that underwent sham-surgery (SHAM) or bilateral transection of the carotid sinus nerves (CSNX) 4 days previously. Rats were placed in whole-body plethysmographs to record ventilatory parameters (frequency of breathing, tidal volume and minute ventilation). After acclimatization, they were exposed to HX (10% O2, 90% N2), HC (5% CO2, 21% O2, 74% N2) or HH (5% CO2, 10% O2, 85% N2) gas challenges for 5 min, followed by 15 min of room-air. The major findings were: (1) the HX, HC and HH challenges elicited robust ventilatory responses in SHAM rats; (2) ventilatory responses elicited by HX alone and HC alone were generally additive in SHAM rats; (3) the ventilatory responses to HX, HC and HH were markedly attenuated in CSNX rats compared to SHAM rats; and (4) ventilatory responses elicited by HX alone and HC alone were not additive in CSNX rats. Although the rats responded to HX after CSNX, CB chemoafferent input was necessary for the response to HH challenge. Thus, secondary peripheral chemoreceptors do not compensate for the loss of chemoreceptor input from the CB in juvenile rats.

scholarly journals Ventilatory responses during and following hypercapnic gas challenge are impaired in male but not female endothelial NOS knock-out mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paulina M. Getsy ◽  
Sripriya Sundararajan ◽  
Walter J. May ◽  
Graham C. von Schill ◽  
Dylan K. McLaughlin ◽  
...  
Keyword(s):  
Tidal Volume ◽  
Minute Ventilation ◽  
Whole Body ◽  
Inspiratory Time ◽  
Male And Female ◽  
Knock Out ◽  
Ventilatory Responses ◽  
Knock Out Mice ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

AbstractThe roles of endothelial nitric oxide synthase (eNOS) in the ventilatory responses during and after a hypercapnic gas challenge (HCC, 5% CO2, 21% O2, 74% N2) were assessed in freely-moving female and male wild-type (WT) C57BL6 mice and eNOS knock-out (eNOS-/-) mice of C57BL6 background using whole body plethysmography. HCC elicited an array of ventilatory responses that were similar in male and female WT mice, such as increases in breathing frequency (with falls in inspiratory and expiratory times), and increases in tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives. eNOS-/- male mice had smaller increases in minute ventilation, peak inspiratory flow and inspiratory drive, and smaller decreases in inspiratory time than WT males. Ventilatory responses in female eNOS-/- mice were similar to those in female WT mice. The ventilatory excitatory phase upon return to room-air was similar in both male and female WT mice. However, the post-HCC increases in frequency of breathing (with decreases in inspiratory times), and increases in tidal volume, minute ventilation, inspiratory drive (i.e., tidal volume/inspiratory time) and expiratory drive (i.e., tidal volume/expiratory time), and peak inspiratory and expiratory flows in male eNOS-/- mice were smaller than in male WT mice. In contrast, the post-HCC responses in female eNOS-/- mice were equal to those of the female WT mice. These findings provide the first evidence that the loss of eNOS affects the ventilatory responses during and after HCC in male C57BL6 mice, whereas female C57BL6 mice can compensate for the loss of eNOS, at least in respect to triggering ventilatory responses to HCC.

Effects of ozone on transepithelial potential of mouse trachea

1993 ◽  
Vol 265 (1) ◽  
pp. L33-L37
Author(s):  
M. Takahashi ◽  
S. R. Kleeberger ◽  
T. L. Croxton
Keyword(s):  
Electrical Potential ◽  
Differential Susceptibility ◽  
Inbred Strains ◽  
Ozone Exposure ◽  
Sodium Absorption ◽  
Epithelial Permeability ◽  
Inbred Strains Of Mice ◽  
Interstrain Difference ◽  
The Mean ◽  
Different Strains

The effects of ozone on tracheal electrical potential were investigated in inbred strains of mice that are differentially susceptible to ozone-induced inflammation. In male mice (9–13 wk), a tracheostomy was made under pentobarbital anesthesia for spontaneous breathing and tracheal potential was measured in the cephalad portion of the bisected trachea using Hanks' salt/agar-capped KCl bridges connected to a pair of calomel half cells. The mean tracheal potentials of five different strains of mice (C3H/HeJ, DBA/2J, C57BL/6J, BALB/cJ, and 129/J) were approximately 10 mV (lumen negative) with no significant interstrain difference. Amiloride reduced mouse tracheal potentials by approximately 70% in both C3H/HeJ and C57BL/6J mice, indicating that sodium absorption is the predominant ion transport across this tissue. Relative to air-exposed controls, acute ozone exposure (2 ppm for 3 h) significantly attenuated tracheal potential of inflammation-susceptible C57BL/6J mice by approximately 50% at 6 h and 40% at 24 h postexposure but had no effect immediately after exposure. The mean tracheal potential of C3H/HeJ mice was not changed by ozone. The differential effect of acute ozone exposure on tracheal potential in C57BL/6J and C3H/HeJ mice is consistent with differential susceptibility to ozone-induced increases in epithelial permeability in these strains.

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