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.

Integration-differentiation and gating of carotid afferent traffic that shapes the respiratory pattern

2003 ◽  
Vol 94 (3) ◽  
pp. 1213-1229 ◽  
Author(s):  
Daniel L. Young ◽  
Frederick L. Eldridge ◽  
Chi-Sang Poon
Keyword(s):  
Carotid Sinus ◽  
Nucleus Tractus Solitarius ◽  
Respiratory Rhythm ◽  
Respiratory Pattern ◽  
Carotid Sinus Nerve ◽  
Short Term ◽  
Time Frequency ◽  
Disease States ◽  
Stop And Go ◽  
Term Potentiation

The phase-dependent plasticity of carotid chemoafferent signaling was studied with electrical stimulation of a carotid sinus nerve during either inspiration or expiration in anesthetized, glomectomized, vagotomized, paralyzed, and ventilated rats. Stroboscopic and interferometric analyses of the resulting phase-contrast disturbances of the respiratory rhythm revealed that carotid chemoafferent traffic was dynamically filtered centrally by a parallel bank of leaky integrators and differentiators, each being logically gated to the inspiratory or expiratory phase in a stop-and-go manner as follows: 1) carotid short-term potentiation of inspiratory drive was mediated by dual integrators that both shortened inspiration and augmented phrenic motor output cooperatively in long and short timescales; 2) carotid short-term depression of respiratory frequency was mediated by a (possibly pontine) integrator that lengthened expiration with a relatively long memory; and 3) carotid “chemoreflex” shortening of expiration was mediated by an occult fast integrator, which, together with carotid short-term depression, formed a differentiator. These effects were modulated anteriorly by integrators in the nucleus tractus solitarius that were “auto-gated” to, or recruited by, the carotid sinus nerve input. Such phase-selective and activity-dependent time-frequency filtering of carotid chemoafferent feedback in parallel neurological-neurodynamic central pathways may profoundly affect respiratory stability during hypoxia and sleep and could contribute to the dynamic optimization of the respiratory pattern and maintenance of homeostasis in health and in disease states.

scholarly journals Carotid sinus nerve transection abolishes the facilitation of breathing that occurs upon cessation of a hypercapnic gas challenge in male mice

2021 ◽  
Author(s):  
Paulina M. Getsy ◽  
Sripriya Sundararajan ◽  
Stephen John Lewis
Keyword(s):  
Carotid Sinus ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Nerve Transection ◽  
Carotid Sinus Nerve ◽  
Ventilatory Responses ◽  
Bilateral Carotid ◽  
Baseline Values ◽  
Freely Moving

Arterial pCO2 elevations increase minute ventilation via activation of chemosensors within the carotid body (CB) and brainstem. Although the roles of CB chemoafferents in the hypercapnic (HC) ventilatory response have been investigated, there are no studies reporting the role of these chemoafferents in the ventilatory responses to a HC challenge or the responses that occur upon return to room-air, in freely-moving mice. This study found that a HC challenge (5%CO2, 21% O2, 74% N2 for 15 min) elicited an array of responses, including increases in frequency of breathing (accompanied by decreases in inspiratory and expiratory times), and increases in tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives in sham-operated (SHAM) adult male C57BL6 mice, and that return to room-air elicited a brief excitatory phase followed by gradual recovery of all parameters toward baseline values over a 15 min period. The array of ventilatory responses to the HC challenge in mice with bilateral carotid sinus nerve transection (CSNX) performed 7 days previously, occurred more slowly but reached similar maxima as SHAM mice. A major finding was responses upon return to room-air were dramatically lower in CSNX mice than SHAM mice, and the parameters returned to baseline values within 1-2 min in CSNX mice, whereas it took much longer in SHAM mice. These findings are the first evidence that CB chemoafferents play a key role in initiating the ventilatory responses to HC challenge in C57BL6 mice and are essential for the expression of post-HC ventilatory responses.

scholarly journals Estradiol Protects Against Cardiorespiratory Dysfunctions and Oxidative Stress in Intermittent Hypoxia

SLEEP ◽  
2017 ◽  
Vol 40 (8) ◽  
Author(s):  
Sofien Laouafa ◽  
Alexandra Ribon-Demars ◽  
François Marcouiller ◽  
Damien Roussel ◽  
Aida Bairam ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Rate ◽  
Intermittent Hypoxia ◽  
Minute Ventilation ◽  
Female Rats ◽  
Whole Body ◽  
Sprague Dawley ◽  
Ventilatory Responses ◽  
Reduced Body ◽  
And Oxidative Stress

Abstract Study Objectives We tested the hypothesis that estradiol (E2) protects against cardiorespiratory disorders and oxidative stress induced by chronic intermittent hypoxia (CIH) in adult female rats. Methods Sprague-Dawley female rats (230–250 g) were ovariectomized and implanted with osmotic pumps delivering vehicle or E2 (0.5 mg/kg/d). After 14 days of recovery, the rats were exposed to CIH (21%–10% O2: 8 h/d, 10 cycles per hour) or room air (RA). After 7 days of CIH or RA exposure, we measured arterial pressures (tail cuff), metabolic rate (indirect calorimetry), minute ventilation, the frequency of sighs and apneas at rest, and ventilatory responses to hypoxia and hypercapnia (whole body plethysmography). We collected the cerebral cortex, brainstem, and adrenal glands to measure the activity of NADPH and xanthine oxidase (pro-oxidant enzymes), glutathione peroxidase, and the mitochondrial and cytosolic superoxide dismutase (antioxidant enzymes) and measured lipid peroxidation and advanced oxidation protein products (markers of oxidative stress). Results CIH increased arterial pressure, the frequency of apnea at rest, and the hypoxic and hypercapnic ventilatory responses and reduced metabolic rate. CIH also increased oxidant enzyme activities and decreased antioxidant activity in the cortex. E2 treatment reduced body weight and prevented the effects of CIH. Conclusions E2 prevents cardiorespiratory disorders and oxidative stress induced by CIH. These observations may help to better understand the underlying mechanisms linking menopause and occurrence of sleep apnea in women and highlight a potential advantage of hormone therapy.

Effect of a synthetic progestin on ventilatory response to hypoxia in anesthetized rats

1989 ◽  
Vol 67 (5) ◽  
pp. 1754-1758 ◽  
Author(s):  
H. Kimura ◽  
M. Mikami ◽  
T. Kuriyama ◽  
Y. Fukuda
Keyword(s):  
Regulatory Mechanism ◽  
Carotid Sinus ◽  
Ventilatory Response ◽  
Break Point ◽  
Male Rat ◽  
Carotid Sinus Nerve ◽  
Ventilatory Responses ◽  
Chlormadinone Acetate ◽  
Ventilatory Depression ◽  
Ventilatory Response To Hypoxia

Effects on ventilatory responses to progressive isocapnic hypoxia of a synthetic potent progestin, chlormadinone acetate (CMA), were determined in the halothane-anesthetized male rat. Ventilation during the breathing of hyperoxic gas was largely unaffected by treatment with CMA when carotid chemoreceptor afferents were kept intact. The sensitivity to hypoxia evaluated by hyperbolic regression analysis of the response curve did not differ between the control and CMA groups. The reduction of ventilation after bilateral section of the carotid sinus nerve (CSN) in hyperoxia was less severe in CMA-treated than in untreated animals. Furthermore, the CMA-treated rats showed a larger increase in ventilation during the hypoxia test and a lower PO2 break point for ventilatory depression. Inhibition of hypoxic ventilatory depression by CMA persisted even after the denervation of CSN. We conclude that exogenous progestin likely protects regulatory mechanism(s) for respiration against hypoxic depression through a stimulating action independent of carotid chemoreceptor afferents and without a change in the sensitivity of the ventilatory response to hypoxia.

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.

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 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.

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.

scholarly journals Mice and Rats Display Different Ventilatory, Hematological, and Metabolic Features of Acclimatization to Hypoxia

2021 ◽  
Vol 12 ◽  
Author(s):  
Christian Arias-Reyes ◽  
Jorge Soliz ◽  
Vincent Joseph
Keyword(s):  
High Altitude ◽  
Minute Ventilation ◽  
Rattus Rattus ◽  
Hemoglobin Concentration ◽  
Whole Body ◽  
Ecological Niches ◽  
House Mice ◽  
Sprague Dawley ◽  
Mitochondrial Oxygen Consumption ◽  
Sd Rats

Phylogeographic studies showed that house mice (Mus musculus) originated in the Himalayan region, while common rats (Rattus rattus and Rattus norvegicus) come from the lowlands of China and India. Accordingly, it has been proposed that its origins gave mice, but not rats, the ability to invade ecological niches at high altitudes (pre-adaptation). This proposal is strongly supported by the fact that house mice are distributed throughout the world, while common rats are practically absent above 2,500 m. Considering that the ability of mammals to colonize high-altitude environments (&gt;2,500 m) is limited by their capability to tolerate reduced oxygen availability, in this work, we hypothesize that divergences in the ventilatory, hematological, and metabolic phenotypes of mice and rats establish during the process of acclimatization to hypoxia (Hx). To test this hypothesis male FVB mice and Sprague-Dawley (SD) rats were exposed to Hx (12% O2) for 0 h (normoxic controls), 6 h, 1, 7, and 21 days. We assessed changes in ventilatory [minute ventilation (VE), respiratory frequency (fR), and tidal volume (VT)], hematological (hematocrit and hemoglobin concentration), and metabolic [whole-body O2 consumption (VO2) and CO2 production (VCO2), and liver mitochondrial oxygen consumption rate (OCR) parameters]. Compared to rats, results in mice show increased ventilatory, metabolic, and mitochondrial response. In contrast, rats showed quicker and higher hematological response than mice and only minor ventilatory and metabolic adjustments. Our findings may explain, at least in part, why mice, but not rats, were able to colonize high-altitude habitats.

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)

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