Control of ventilation in adult rats hypoxic in the neonatal period

1990 ◽  
Vol 259 (4) ◽  
pp. R836-R841 ◽  
Author(s):  
S. Okubo ◽  
J. P. Mortola
Keyword(s):  
Neonatal Period ◽  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Lower Sensitivity ◽  
Adult Rats ◽  
Genetic Characteristics ◽  
Ventilatory Responses ◽  
Central Inhibition ◽  
Inspiratory Activity ◽  
High Altitude Natives

Three groups of 50-day-old (i.e., postpuberty) rats have been studied: controls, rats exposed to 6 days of hypoxia [inspired fraction of O2 (FIo2) = 10% O2] when newborn (Nb-Hypox), and rats exposed to the same level and duration of hypoxia after weaning (Ad-Hypox). Ventilation during normoxic breathing was higher in Nb-Hypox than in controls or Ad-Hypox. The ventilatory response to acute hypoxia (10 min of 10% O2) was about one-half in Nb-Hypox than in the other two groups. Additional measurements performed on Nb-Hypox and controls showed minimal or no differences between the two groups in the ventilatory responses to hyperoxia and hypercapnia, heart rate and blood pressure at various FIO2, and blood biochemistry. Analysis of the Hering-Breuer reflexes, during barbiturate anesthesia, suggested a decreased central inhibition on inspiratory activity in Nb-Hypox, which with a lower sensitivity to inputs from the peripheral chemoreceptors may contribute to the normoxic hyperventilation and the blunted response to acute hypoxia. The ventilatory patterns of Nb-Hypox rats bear numerous similarities with those of high-altitude natives and could suggest that the highlander's ventilatory responses are not genetic characteristics but relate to chronic hypoxia early in life.

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.

Ventilatory responses to hypoxia in rats pretreated with nonpeptide NK1 receptor antagonist CP-96,345

1994 ◽  
Vol 76 (4) ◽  
pp. 1528-1532 ◽  
Author(s):  
G. T. De Sanctis ◽  
F. H. Green ◽  
X. Jiang ◽  
M. King ◽  
J. E. Remmers
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Frequency Component ◽  
Nk1 Receptor ◽  
Adult Rats ◽  
Nk1 Receptors ◽  
Before And After ◽  
Sites Of Action

This study reports experiments designed to evaluate the role of neurokinin-1 (NK1) receptors for substance P (SP) in the ventilatory response to acute hypoxia. Ventilation was measured by indirect plethysmography in eight unanesthetized unrestrained adult rats before and after bolus injection of 1, 5, or 10 mg/kg (ip) of CP-96,345 (Pfizer), a potent nonpeptide competitive antagonist of the SP NK1 receptor. Ventilation was measured while the rats breathed air or 8% O2–92% N2 with and without administration of SP antagonist. Pretreatment with CP-96,345 decreased the magnitude of the hypoxic response in a dose-dependent fashion. Minute ventilation in rats pretreated with CP-96,345 was reduced by 22.1% (P < 0.05) at the highest dose (10 mg/kg), largely because of an attenuation of the frequency component. Although both control and treated rats responded to hypoxia with a decrease in duration of inspiration and expiration rats pretreated with CP-96,345 displayed a smaller decrease in inspiration and expiration than control rats (P < 0.05). We have recently shown that neuropeptide-containing fibers are important for mediating the tachypnic response during acute isocapnic hypoxia in rats. The attenuation in minute ventilation at the highest dose (10 mg/kg) is comparable in magnitude to the attenuation observed with neonatal capsaicin treatment, which permanently ablates neuropeptide-containing unmyelinated fibers. Accordingly, this previously reported role of capsaicin-sensitive nerves in the hypoxic ventilatory response of rats is probably attributable to released SP acting at NK1 receptors. One of the likely sites of action of SP antagonists is the carotid body.(ABSTRACT TRUNCATED AT 250 WORDS)

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 Adenosine receptors mediate the hypoxic ventilatory response but not the hypoxic metabolic response in the naked mole rat during acute hypoxia

2015 ◽  
Vol 282 (1800) ◽  
pp. 20141722 ◽  
Author(s):  
Matthew E. Pamenter ◽  
Yvonne A. Dzal ◽  
William K. Milsom
Keyword(s):  
Adenosine Receptors ◽  
Metabolic Response ◽  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Thermal Response ◽  
Hypoxia Tolerance ◽  
Hypoxic Ventilatory Response ◽  
Adenosine Receptor Antagonist ◽  
Ventilatory Responses ◽  
Mole Rat

Naked mole rats are the most hypoxia-tolerant mammals identified; however, the mechanisms underlying this tolerance are poorly understood. Using whole-animal plethysmography and open-flow respirometry, we examined the hypoxic metabolic response (HMR), hypoxic ventilatory response (HVR) and hypoxic thermal response in awake, freely behaving naked mole rats exposed to 7% O 2 for 1 h. Metabolic rate and ventilation each reversibly decreased 70% in hypoxia (from 39.6 ± 2.9 to 12.1 ± 0.3 ml O 2 min −1 kg −1 , and 1412 ± 244 to 417 ± 62 ml min −1 kg −1 , respectively; p < 0.05), whereas body temperature was unchanged and animals remained awake and active. Subcutaneous injection of the general adenosine receptor antagonist aminophylline (AMP; 100 mg kg −1 , in saline), but not control saline injections, prevented the HVR but had no effect on the HMR. As a result, AMP-treated naked mole rats exhibited extreme hyperventilation in hypoxia. These animals were also less tolerant to hypoxia, and in some cases hypoxia was lethal following AMP injection. We conclude that in naked mole rats (i) hypoxia tolerance is partially dependent on profound hypoxic metabolic and ventilatory responses, which are equal in magnitude but occur independently of thermal changes in hypoxia, and (ii) adenosine receptors mediate the HVR but not the HMR.

Interaction between CO2 production and ventilation in the hypoxic kitten

1993 ◽  
Vol 74 (2) ◽  
pp. 905-910 ◽  
Author(s):  
J. P. Mortola ◽  
T. Matsuoka
Keyword(s):  
Breathing Pattern ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Co2 Production ◽  
Depressant Effect ◽  
Arterial Pco2 ◽  
Ventilatory Responses ◽  
Parallel Increase ◽  
Shallow Breathing

We hypothesized that in the hypoxic newborn the drop in metabolic rate, and particularly in CO2 production (VCO2), contributes to the magnitude of the ventilatory response. Experiments were performed on unanesthetized newborn kittens in a warm [28–30 degrees C ambient temperature (Ta)] or cold (20 degrees C) environment. Breathing pattern and gaseous metabolism were measured by the barometric technique and the inflow-outflow O2 and CO2 difference, respectively. At 30 degrees C, hypoxia (10% O2) decreased VCO2 and induced rapid and shallow breathing, with little effect on minute ventilation (VE). Normoxic exposure to 20 degrees C determined a parallel increase in VE and metabolism; at this Ta, hypoxia decreased VCO2 more than at the higher Ta, and the drop in tidal volume (VT) was also proportionally larger; hence, at 20 degrees C, hypoxic VE was markedly below the normoxic values. Despite these changes in breathing pattern, at neither Ta during hypoxia did arterial PCO2 increase above the normoxic value; in fact, arterial PCO2 at 20 degrees C was slightly decreased because of the important drop in VCO2. Exposure to hypoxia with a CO2 load (inspired CO2 = 1, 3, or 5%) did not abolish the hypometabolic response; the hypoxic depressant effect on VT was either unchanged (by 1% CO2), completely offset (by 3% CO2), or reversed (by 5% CO2), with parallel effects on VE. The results are consistent with the hypothesis that in the newborn the level of CO2, by controlling VT, could represent a link between the metabolic and ventilatory responses to acute hypoxia.

Recovery of peripheral chemoreceptor function after denervation in ponies

1980 ◽  
Vol 49 (6) ◽  
pp. 964-970 ◽  
Author(s):  
G. E. Bisgard ◽  
H. V. Forster ◽  
J. P. Klein
Keyword(s):  
Chronic Hypoxia ◽  
Carotid Sinus ◽  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Time Dependent ◽  
Partial Recovery ◽  
Dependent Manner ◽  
Normal Response ◽  
Peripheral Chemoreceptor ◽  
Ventilatory Responses

Resting ventilation (PaCO2) and ventilatory responses to acute hypoxia and to intravenous NaCN were assessed over a 4-yr period following cutting of the carotid sinus nerves and stripping the adventitia of the aortic arch. The data indicated essentially complete loss of peripheral chemoreceptor function immediately after surgery and hypoventilation during normoxia (delta PaCO2 = +8.7 Torr). There was a time-dependent, partial recovery of peripheral chemoreceptor function between 2 and 22 mo after surgery. Approximately 10% of the ventilatory response to iv NaCN returned, and 30-40% of the normal response to acute hypoxia was restored. Resting PaCO2 was no longer significantly elevated above normal by 22 mo after surgery. Four years after surgery these animals were unable to sustain normal ventilatory acclimatization to chronic hypoxia just as in an earlier study in the same ponies. Experiments carried out under anesthesia showed that recovered peripheral chemoreceptor sensitivity was not present in the carotid chemoreceptor area. However, sectioning of the aortic nerve caused the animals to again hypoventilate during acute hypoxia, and it nearly eliminated the ventilatory response to NaCN, but normal eucapnic ventilation was retained. We conclude that in the pony aortic chemoreceptors become functional in a time-dependent manner following carotid body denervation.

Ventilatory responses to acute and chronic hypoxia in mice: effects of dopamine D2 receptors

2000 ◽  
Vol 89 (3) ◽  
pp. 1142-1150 ◽  
Author(s):  
K. A. Huey ◽  
M. J. Low ◽  
M. A. Kelly ◽  
R. Juarez ◽  
J. M. Szewczak ◽  
...  
Keyword(s):  
Chronic Hypoxia ◽  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Genetically Engineered ◽  
Time Dependent ◽  
Male Mice ◽  
Wild Type ◽  
Ventilatory Responses ◽  
Type D ◽  
Gender Specific

We used genetically engineered D2 receptor-deficient [D2-(−/−)] and wild-type [D2-(+/+)] mice to test the hypothesis that dopamine D2 receptors modulate the ventilatory response to acute hypoxia [hypoxic ventilatory response (HVR)] and hypercapnia [hypercapnic ventilatory response (HCVR)] and time-dependent changes in ventilation during chronic hypoxia. HVR was independent of gender in D2-(+/+) mice and significantly greater in D2-(−/−) than in D2-(+/+) female mice. HCVR was significantly greater in female D2–(+/+) mice than in male D2-(+/+) and was greater in D2-(−/−) male mice than in D2-(+/+) male mice. Exposure to hypoxia for 2–8 days was studied in male mice only. D2-(+/+) mice showed time-dependent increases in “baseline” ventilation (inspired Po 2 = 214 Torr) and hypoxic stimulated ventilation (inspired Po 2 = 70 Torr) after 8 days of acclimatization to hypoxia, but D2-(−/−) mice did not. Hence, dopamine D2receptors modulate the acute HVR and HCVR in mice in a gender-specific manner and contribute to time-dependent changes in ventilation and the acute HVR during acclimatization to hypoxia.

Fetal chemoreception: a developing story

1996 ◽  
Vol 8 (3) ◽  
pp. 471 ◽  
Author(s):  
DF Teitel
Keyword(s):  
Carbon Dioxide ◽  
Ventilatory Response ◽  
Current Knowledge ◽  
Chemical Stimulus ◽  
Lung Inflation ◽  
Ventilatory Responses ◽  
Central Inhibition ◽  
Chemical Stimuli ◽  
The Difference ◽  
Efficient Uptake

The central and peripheral chemoreceptors are critical to the efficient uptake and delivery of oxygen and the removal of carbon dioxide after birth. However, the importance and activity of fetal chemoreception has been questioned, since oxygen uptake and carbon dioxide removal are not regulated in the lungs in the fetus. Early studies suggested that chemotransduction-the conversion of a chemical stimulus to cardiovascular and ventilatory responses via the integration of chemoreceptor stimulation, neural afferent activity and neurohormonal effector mechanisms-was immature in its individual components or their interaction. However, it now appears that the chemoreceptor cascade is structurally and functionally intact in the late-term fetus, and responds actively to normal and other chemical stimuli. The differences between fetal and postnatal chemotransduction appear to be primarily dependent on the central inhibition of the ventilatory response, the inhibitory area being localized to the lateral pons. It appears to be mediated in part by a placental factor which is removed at birth, allowing for the expression of the ventilatory response. The suppression of this response is also responsible for the difference in the heart rate response: the postnatal tachycardia is caused by the lung inflation reflex; when abolished, bradycardia is seen, just as in the fetus. Despite the suppression of the ventilatory component of chemoreception, the fetal carotid chemoreceptor is more important than the aortic, even though it has been considered to be more important to ventilatory than to cardiovascular stability. This review discusses current knowledge of the various components of the mature chemoreceptor cascade, and presents the fetal story within that framework.

scholarly journals Ventilatory responses to acute hypoxia and hypercapnia in humans with a patent foramen ovale

2019 ◽  
Vol 126 (3) ◽  
pp. 730-738 ◽  
Author(s):  
James T. Davis ◽  
Lindsey M. Boulet ◽  
Alyssa M. Hardin ◽  
Alex J. Chang ◽  
Andrew T. Lovering ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
High Altitude ◽  
Patent Foramen Ovale ◽  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Acute Exposure ◽  
Foramen Ovale ◽  
Hypoxic Ventilatory Response ◽  
Ventilatory Responses ◽  
Peripheral Chemoreflex

Subjects with a patent foramen ovale (PFO) have blunted ventilatory acclimatization to high altitude compared with subjects without PFO. The blunted response observed could be because of differences in central and/or peripheral respiratory chemoreflexes. We hypothesized that compared with subjects without a PFO (PFO−), subjects with a PFO (PFO+) would have blunted ventilatory responses to acute hypoxia and hypercapnia. Sixteen PFO+ subjects (9 female) and 15 PFO− subjects (8 female) completed four 20-min trials on the same day: 1) normoxic hypercapnia (NH), 2) hyperoxic hypercapnia (HH), 3) isocapnic hypoxia (IH), and 4) poikilocapnic hypoxia (PH). Hypercapnic trials were completed before the hypoxic trials, the order of the hypercapnic (NH & HH) and hypoxic (IH & PH) trials were randomized, and trials were separated by ≥40 min. During the NH trials but not the HH trials subjects who were PFO+ had a blunted hypercapnic ventilatory response compared with subjects who were PFO− (1.41 ± 0.46 l·min−1·mmHg−1 vs. 1.98 ± 0.71 l·min−1·mmHg−1, P = 0.02). There were no differences between the PFO+ and PFO− subjects with respect to the acute hypoxic ventilatory response during IH and PH trials. Hypoxic ventilatory depression was similar between subjects who were PFO+ and PFO− during IH. These data suggest that compared with subjects who were PFO−, subjects who were PFO+ have normal ventilatory chemosensitivity to acute hypoxia but blunted ventilatory chemosensitivity to carbon dioxide, possibly because of reduced carbon dioxide sensitivity of either the central and/or the peripheral chemoreceptors. NEW & NOTEWORTHY Patent foramen ovale (PFO) is found in ~25%–40% of the population. The presence of a PFO appears to be associated with blunted ventilatory responses during acute exposure to normoxic hypercapnia. The reason for this blunted ventilatory response during acute exposure to normoxic hypercapnia is unknown but may suggest differences in either central and/or peripheral chemoreflex contribution to hypercapnia.

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