Stress-induced attenuation of the hypercapnic ventilatory response in awake rats

2001 ◽  
Vol 90 (5) ◽  
pp. 1729-1735 ◽  
Author(s):  
Richard Kinkead ◽  
Lydie Dupenloup ◽  
Nadine Valois ◽  
Roumiana Gulemetova
Keyword(s):  
Control System ◽  
Immobilization Stress ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Respiratory Control ◽  
Whole Body ◽  
Respiratory Homeostasis ◽  
Whole Body Plethysmography ◽  
Ventilatory Response To Hypoxia ◽  
Awake Rats

To test the hypothesis that stress alters the performance of the respiratory control system, we compared the acute (20 min) responses to moderate hypoxia and hypercapnia of rats previously subjected to immobilization stress (90 min/day) with responses of control animals. Ventilatory measurements were performed on awake rats using whole body plethysmography. Under baseline conditions, there were no differences in minute ventilation between stressed and unstressed groups. Rats previously exposed to immobilization stress had a 45% lower ventilatory response to hypercapnia (inspiratory CO2 fraction = 0.05) than controls. In contrast, stress exposure had no statistically significant effect on the ventilatory response to hypoxia (inspiratory O2 fraction = 0.12). Stress-induced attenuation of the hypercapnic response was associated with reduced tidal volume and inspiratory flow increases; the frequency and timing components of the response were not different between groups. We conclude that previous exposure to a stressful condition that does not constitute a direct challenge to respiratory homeostasis can elicit persistent (≥24 h) functional plasticity in the ventilatory control system.

Endogenous brain erythropoietin is a potent sex-specific respiratory stimulant in adult and newborn mice

2015 ◽  
Vol 118 (11) ◽  
pp. 1386-1395 ◽  
Author(s):  
Orlane Ballot ◽  
Vincent Joseph ◽  
Jorge Soliz
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Whole Body ◽  
Newborn Mice ◽  
Male And Female ◽  
Female Mice ◽  
Specific Effects ◽  
Respiratory Stimulant ◽  
Males And Females ◽  
Whole Body Plethysmography

We tested the hypothesis that endogenous brain Epo is a respiratory stimulant. Adult (3 mo) and newborn (10 days) male and female mice received an intracisternal (cisterna magna) injection of soluble Epo receptor (sEpoR; competes with EpoR to bind Epo; 50 μg/ml) or vehicle (0.1% BSA in PBS). Twenty-four hours after injection, we used whole body plethysmography to record minute ventilation (V̇e) tidal volume (VT), respiratory frequency ( fR), O2 consumption (V̇o2), and CO2 production (V̇co2) under normoxia and progressive exposure to hypoxia (12-10-6% O2; 10 min each). In adult male and female mice sEpoR decreased normoxic V̇e (−25%), due to a decrease of VT in males and fR in females. Moreover, sEpoR injection decreased the ventilatory response to 12% O2, assessed as V̇e/V̇o2 or V̇e/V̇co2, in male but not in female mice. In newborn male and female mice sEpoR decreased V̇e (−37% in males, −59% in females) and VT (−38% in males, −47% in females) in normoxia and fR in females. During hypoxia, sEpoR decreased V̇e/V̇o2 and V̇e/V̇co2 in mice of both sexes. Upon extreme hypoxia (6% O2), the newborn mice treated with sEpoR showed respiratory depression, signs of asphyxia (gasping) and a high mortality rate in males and females. We concluded that endogenous brain Epo is a potent respiratory stimulant under normoxia and hypoxia in adult and newborn mice. Because sex-specific effects are different in newborn male and female, sex steroids secreted at different ages mice appear to modulate the effects of Epo on respiratory regulation in normoxia and in response to hypoxia.

Prenatal blockade of estradiol synthesis impairs respiratory and metabolic responses to hypoxia in newborn and adult rats

2004 ◽  
Vol 287 (3) ◽  
pp. R612-R618 ◽  
Author(s):  
V. D. Doan ◽  
S. Gagnon ◽  
V. Joseph
Keyword(s):  
Minute Ventilation ◽  
Respiratory Control ◽  
Late Gestation ◽  
Whole Body ◽  
Adult Rats ◽  
Pregnant Rats ◽  
Subcutaneous Injections ◽  
Hyperoxic Exposure ◽  
Estradiol Synthesis ◽  
Whole Body Plethysmography

We tested the hypothesis that estradiol modifies respiratory control in pregnant rats and participates in the development of respiratory chemoreflexes in fetuses. Pregnant rats ( n = 12) received daily subcutaneous injections of vehicle (Veh, n = 6) or 4-androsten-4-ol-3,17-dione acetate (ATD; inhibitor of estradiol synthesis; n = 6; 5 mg/day in vehicle) from gestational day 16 (G16) to delivery. Baseline ventilation (whole body plethysmography) and metabolic rate [oxygen consumption (V̇o2)] were determined at G14 and G20, in pups [on postnatal day 3 (P3) and P20] and in adult rats (on P70) born to Veh- or ATD-treated mothers. Hypoxic chemoreflex was assessed in P3 rats by acute exposure to 60% O2 and in P20 or P70 rats by moderate hypoxia (12% O2, 30 min). ATD treatment reduced circulating estradiol in pregnant dams at G20 without producing changes in the circulating level of estradiol precursors (testosterone and androstenedione). ATD-treated dams showed impaired respiratory adjustment to late gestation. Pups born to ATD mothers had higher resting V̇o2 (+23% at P3, +21% at P20), respiratory frequency (+15% at P3, +12% at P20), and minute ventilation (+11% at P3, +18% at P20) than pups from Veh mothers. Respiratory decrease during acute hyperoxic exposure at P3 was −9.7% in Veh ( P < 0.05 vs. room air) and only −2.6% ( P = not significant) in ATD pups. In P20 ATD rats, hypoxic ventilatory response was attenuated compared with Veh. In P20 and P70 rats, the drop of V̇o2 in hypoxia (−31% in P70, P < 0.0001) was not observed in ATD rats. We conclude that estradiol secreted during late gestation is necessary for respiratory adjustment to pregnancy and is required for adequate development of respiratory and metabolic control in the offspring.

Ventilatory response to hypoxia in unanesthetized newborn kittens

1988 ◽  
Vol 64 (6) ◽  
pp. 2544-2551 ◽  
Author(s):  
H. Rigatto ◽  
C. Wiebe ◽  
C. Rigatto ◽  
D. S. Lee ◽  
D. Cates
Keyword(s):  
Tidal Volume ◽  
Chest Wall ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Respiratory Frequency ◽  
Quiet Sleep ◽  
Newborn Kitten ◽  
Peripheral Mechanism ◽  
Flow Through ◽  
Ventilatory Response To Hypoxia

We studied the ventilatory response to hypoxia in 11 unanesthetized newborn kittens (n = 54) between 2 and 36 days of age by use of a flow-through system. During quiet sleep, with a decrease in inspired O2 fraction from 21 to 10%, minute ventilation increased from 0.828 +/- 0.029 to 1.166 +/- 0.047 l.min-1.kg-1 (P less than 0.001) and then decreased to 0.929 +/- 0.043 by 10 min of hypoxia. The late decrease in ventilation during hypoxia was related to a decrease in tidal volume (P less than 0.001). Respiratory frequency increased from 47 +/- 1 to 56 +/- 2 breaths/min, and integrated diaphragmatic activity increased from 14.9 +/- 0.9 to 20.2 +/- 1.4 arbitrary units; both remained elevated during hypoxia (P less than 0.001). Younger kittens (less than 10 days) had a greater decrease in ventilation than older kittens. These results suggest that the late decrease in ventilation during hypoxia in the newborn kitten is not central but is due to a peripheral mechanism located in the lungs or respiratory pump and affecting tidal volume primarily. We speculate that either pulmonary bronchoconstriction or mechanical uncoupling of diaphragm and chest wall may be involved.

Living high-training low increases hypoxic ventilatory response of well-trained endurance athletes

2002 ◽  
Vol 93 (4) ◽  
pp. 1498-1505 ◽  
Author(s):  
Nathan E. Townsend ◽  
Christopher J. Gore ◽  
Allan G. Hahn ◽  
Michael J. McKenna ◽  
Robert J. Aughey ◽  
...  
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Respiratory Control ◽  
Endurance Athletes ◽  
Hypoxic Exposure ◽  
Dependent Manner ◽  
Hypoxic Ventilatory Response ◽  
Ambient Conditions ◽  
Altitude Exposure ◽  
End Tidal

This study determined whether “living high-training low” (LHTL)-simulated altitude exposure increased the hypoxic ventilatory response (HVR) in well-trained endurance athletes. Thirty-three cyclists/triathletes were divided into three groups: 20 consecutive nights of hypoxic exposure (LHTLc, n = 12), 20 nights of intermittent hypoxic exposure (four 5-night blocks of hypoxia, each interspersed with 2 nights of normoxia, LHTLi, n = 10), or control (Con, n = 11). LHTLc and LHTLi slept 8–10 h/day overnight in normobaric hypoxia (∼2,650 m); Con slept under ambient conditions (600 m). Resting, isocapnic HVR (ΔV˙e/ΔSpO2 , whereV˙e is minute ventilation and SpO2 is blood O2 saturation) was measured in normoxia before hypoxia (Pre), after 1, 3, 10, and 15 nights of exposure (N1, N3, N10, and N15, respectively), and 2 nights after the exposure night 20 (Post). Before each HVR test, end-tidal Pco 2(Pet CO2 ) and V˙e were measured during room air breathing at rest. HVR (l · min−1 · %−1) was higher ( P < 0.05) in LHTLc than in Con at N1 (0.56 ± 0.32 vs. 0.28 ± 0.16), N3 (0.69 ± 0.30 vs. 0.36 ± 0.24), N10 (0.79 ± 0.36 vs. 0.34 ± 0.14), N15 (1.00 ± 0.38 vs. 0.36 ± 0.23), and Post (0.79 ± 0.37 vs. 0.36 ± 0.26). HVR at N15 was higher ( P < 0.05) in LHTLi (0.67 ± 0.33) than in Con and in LHTLc than in LHTLi. Pet CO2 was depressed in LHTLc and LHTLi compared with Con at all points after hypoxia ( P < 0.05). No significant differences were observed for V˙e at any point. We conclude that LHTL increases HVR in endurance athletes in a time-dependent manner and decreases Pet CO2 in normoxia, without change inV˙e. Thus endurance athletes sleeping in mild hypoxia may experience changes to the respiratory control system.

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.

Ventilatory response to transient hyperoxia in head injury hyperventilation

1980 ◽  
Vol 49 (1) ◽  
pp. 52-58 ◽  
Author(s):  
A. G. Leitch ◽  
J. E. McLennan ◽  
S. Balkenhol ◽  
R. L. McLaurin ◽  
R. G. Loudon
Keyword(s):  
Head Injury ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Respiratory Control ◽  
Normal Subjects ◽  
Respiratory Alkalosis ◽  
Cerebral Injury ◽  
Peripheral Chemoreceptor ◽  
Male Patients ◽  
Almost All

We have measured breath-by-breath instantaneous minute ventilation (VIinst) before, during, and after the administration of 10 breaths of 100% oxygen to seven male patients with head injury hyperventilation. The patients were hypoxemic (PaO2 61.2 ± 6.3) and hypocapnic (PaCO2 26.6 ± 5.9) with a respiratory alkalosis (pH 7.53 ± 0.06) while breathing air. Following the oxygen VIinst fell on the average by 40 ± 12.7% from 16.06 ± 3.75 1.min-1 to a minimum of 9.73 ± 3.20 1.min-1 at 20.4 ± 2.9 s after the first breath of oxygen. In the majority of our hyperventilating patients, almost all of the resting hyperventilation could be abolished transiently by 100% oxygen. This fall in ventilation represents the peripheral chemoreceptor contribution to resting ventilation and is increased in the head injury patients in comparison with normal subjects breathing air or hypoxic gas mixtures, altitude-acclimatized subjects and patients who are hypoxic because of chronic bronchitis or interstitial lung disease. We suggest that the increased reflex hypoxic drive to ventilation found in our patients is secondary to their cerebral injury, resulting in a reduction of descending cortical inhibitory influences on the medullary respiratory control centers.

Calcium/calmodulin-dependent kinase II mediates critical components of the hypoxic ventilatory response within the nucleus of the solitary tract in adult rats

2005 ◽  
Vol 289 (3) ◽  
pp. R871-R876 ◽  
Author(s):  
Stephen R. Reeves ◽  
Edwin S. Carter ◽  
Shang Z. Guo ◽  
David Gozal
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Respiratory Frequency ◽  
Whole Body ◽  
Solitary Tract ◽  
Hypoxic Ventilatory Response ◽  
Adult Rats ◽  
Osmotic Pumps ◽  
Calcium Calmodulin Dependent

Calcium/calmodulin-dependent kinase II (CaMKII) is an ubiquitous second messenger that is highly expressed in neurons, where it has been implicated in some of the pathways regulating neuronal discharge as well as N-methyl-d-aspartate receptor-mediated synaptic plasticity. The full expression of the mammalian hypoxic ventilatory response (HVR) requires intact central relays within the nucleus of the solitary tract (NTS), and neural transmission of hypoxic afferent input is mediated by glutamatergic receptor activity, primarily through N-methyl-d-aspartate receptors. To examine the functional role of CaMKII in HVR, KN-93, a highly selective antagonist of CaMKII, was microinjected in the NTS via bilaterally placed osmotic pumps in freely behaving adult male Sprague-Dawley rats for 3 days. Vehicle-loaded osmotic pumps were surgically placed in control animals, and adequate placement of cannulas was ascertained for all animals. HVR was measured using whole body plethysmography during exposure to 10% O2-balance N2 for 20 min. Compared with control rats, KN-93 administration elicited marked attenuations of peak HVR (pHVR) but did not modify normoxic minute ventilation. Differences in pHVR were primarily attributable to diminished respiratory frequency recruitments during pHVR without significant differences in tidal volume. These findings indicate that CaMKII activation in the NTS mediates respiratory frequency components of the ventilatory response to acute hypoxia; however, CaMKII activity does not appear to underlie components of normoxic ventilation.

Possible alterations in brain monoamine metabolism during hypoxia-induced tachypnea in cats

1980 ◽  
Vol 49 (5) ◽  
pp. 769-777 ◽  
Author(s):  
H. Gautier ◽  
M. Bonora
Keyword(s):  
Control Systems ◽  
Ventilatory Response ◽  
Respiratory Control ◽  
Monoamine Metabolism ◽  
Moderate Hypoxia ◽  
Significant Depression ◽  
Brain Monoamine ◽  
Conscious Animals ◽  
Ventilatory Response To Hypoxia ◽  
Stimulation Of

In carotid body-denervated cats, moderate hypoxia, or even normoxia when compared to hyperoxia, provokes a significant depression of the respiratory output. This is observed in conscious or anesthetized or decerebrated animals. On the other hand, more severe hypoxia induces tachypnea (hypoxic tachypnea of Miller and Tenney, Respir. Physiol. 23: 31-39, 1975) in conscious cats, whereas the same hypoxia is followed by marked respiratory depression or apnea in the anesthetized or decerebrated animals. Hypoxic tachypnea can be partly or completely reversed by injection of dopa or xanthines such as caffeine or aminophylline. This suggests that alterations in brain monoamine metabolism by hypoxia may be responsible for the alterations in suprapontine respiratory control systems, resulting the tachypnea. Mild hypercapnia can also reverse hypoxic tachypnea. It is concluded that the ventilatory response to hypoxia of conscious animals results from stimulation of peripheral chemoreceptors, inhibition of brain stem neurons, and finally involvement of suprapontine structures that seems to be mediated by depletion of monoamines.

Ventilatory response to hyperoxia in newborn mice heterozygous for the transcription factor Phox2b

2006 ◽  
Vol 290 (6) ◽  
pp. R1691-R1696 ◽  
Author(s):  
N. Ramanantsoa ◽  
V. Vaubourg ◽  
S. Dauger ◽  
B. Matrot ◽  
G. Vardon ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Whole Body ◽  
Wild Type ◽  
Peripheral Chemoreceptor ◽  
Newborn Mice ◽  
Apnea Duration ◽  
Autonomic Reflex ◽  
Hypoventilation Syndrome

Heterozygous mutations of the transcription factor PHOX2B have been found in most patients with central congenital hypoventilation syndrome, a rare disease characterized by sleep-related hypoventilation and impaired chemosensitivity to sustained hypercapnia and sustained hypoxia. PHOX2B is a master regulator of autonomic reflex pathways, including peripheral chemosensitive pathways. In the present study, we used hyperoxic tests to assess the strength of the peripheral chemoreceptor tonic drive in Phox2b+/− newborn mice. We exposed 69 wild-type and 67 mutant mice to two hyperoxic tests (12-min air followed by 3-min 100% O2) 2 days after birth. Breathing variables were measured noninvasively using whole body flow plethysmography. The initial minute ventilation decrease was larger in mutant pups than in wild-type pups: −37% (SD 13) and −25% (SD 18), respectively, P < 0.0001. Furthermore, minute ventilation remained depressed throughout O2 exposure in mutants, possibly because of their previously reported impaired CO2 chemosensitivity, whereas it returned rapidly to the normoxic level in wild-type pups. Hyperoxia considerably increased total apnea duration in mutant compared with wild-type pups ( P = 0.0001). A complementary experiment established that body temperature was not influenced by hyperoxia in either genotype group and, therefore, did not account for genotype-related differences in the hyperoxic ventilatory response. Thus partial loss of Phox2b function by heterozygosity did not diminish the tonic drive from peripheral chemoreceptors.

Cold stimulates the behavioral response to hypoxia in newborn mice

2009 ◽  
Vol 296 (5) ◽  
pp. R1503-R1511 ◽  
Author(s):  
Bieke Bollen ◽  
Myriam Bouslama ◽  
Boris Matrot ◽  
Yann Rotrou ◽  
Guy Vardon ◽  
...  
Keyword(s):  
Body Temperature ◽  
Stress Responses ◽  
Defense Mechanism ◽  
Whole Body ◽  
Newborn Mice ◽  
Sleep Breathing Disorders ◽  
Arousal Response ◽  
Old Mice ◽  
Whole Body Plethysmography ◽  
Ventilatory Response To Hypoxia

In newborns, hypoxia elicits increased ventilation, arousal followed by defensive movements, and cries. Cold is known to affect the ventilatory response to hypoxia, but whether it affects the arousal response remains unknown. The aim of the present study was to assess the effects of cold on the ventilatory and arousal responses to hypoxia in newborn mice. We designed an original platform measuring noninvasively and simultaneously the breathing pattern by whole body plethysmography, body temperature by infrared thermography, as well as motor and ultrasonic vocal (USV) responses. Six-day-old mice were exposed twice to 10% O2 for 3 min at either cold temperature (26°C) or thermoneutrality (33°C). At 33°C, hypoxia elicited a marked increase in ventilation followed by a small ventilatory decline, small motor response, and almost no USVs. Body temperature was not influenced by hypoxia, and oxygen consumption (V̇o2) displayed minimal changes. At 26°C, hypoxia elicited a slight increase in ventilation with a large ventilatory decline and a large drop of V̇o2. This response was accompanied by marked USV and motor responses. Hypoxia elicited a small decrease in temperature after the return to normoxia, thus precluding any causal influence on the motor and USV responses to hypoxia. In conclusion, cold stimulated arousal and stress responses to hypoxia, while depressing hypoxic hyperpnea. Arousal is an important defense mechanism against sleep-disordered breathing. The dissociation between ventilatory and behavioral responses to hypoxia suggests that deficits in the arousal response associated with sleep breathing disorders cannot be attributed to a depressed hypoxic response.

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