Ventilatory response to acute hypoxia in transgenic mice over-expressing erythropoietin: Effect of acclimation to 3-week hypobaric hypoxia

2007 ◽  
Vol 158 (2-3) ◽  
pp. 243-250 ◽  
Author(s):  
Francisco C. Villafuerte ◽  
Rosa Cárdenas-Alayza ◽  
José Luis Macarlupú ◽  
Carlos Monge-C ◽  
Fabiola León-Velarde
Keyword(s):  
Transgenic Mice ◽  
Hypobaric Hypoxia ◽  
Ventilatory Response ◽  
Acute Hypoxia

Impaired ventilatory acclimatization to hypoxia in female mice overexpressing erythropoietin: unexpected deleterious effect of estradiol in carotid bodies

2010 ◽  
Vol 299 (6) ◽  
pp. R1511-R1520 ◽  
Author(s):  
Max Gassmann ◽  
Christine Pfistner ◽  
Van Diep Doan ◽  
Johannes Vogel ◽  
Jorge Soliz
Keyword(s):  
Transgenic Mice ◽  
Chronic Hypoxia ◽  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Female Mice ◽  
Arterial Blood ◽  
Carotid Bodies ◽  
Central Brain ◽  
Central Response ◽  
The Brain

Apart from enhancing the production of red blood cells, erythropoietin (Epo) alters the ventilatory response when oxygen supply is reduced. We recently demonstrated that Epo's beneficial effect on the ventilatory response to acute hypoxia is sex dependent, with female mice being better able to cope with reduced oxygenation. In the present work, we hypothesized that ventilatory acclimatization to chronic hypoxia (VAH) in transgenic female mice (Tg6) harboring high levels of Epo in the brain and blood will also be improved compared with wild-type (WT) animals. Surprisingly, VAH was blunted in Tg6 female mice. To define whether this phenomenon had a central (brain stem respiratory centers) and/or peripheral (carotid bodies) origin, a bilateral transection of carotid sinus nerve (chemodenervation) was performed. This procedure allowed the analysis of the central response in the absence of carotid body information. Interestingly, chemodenervation restored the VAH in Tg6 mice, suggesting that carotid bodies were responsible for the blunted response. Coherently with this observation, the sensitivity to oxygen alteration in arterial blood (Dejour test) after chronic hypoxia was lower in transgenic carotid bodies compared with the WT control. As blunted VAH occurred in female but not male transgenic mice, the involvement of sex female steroids was obvious. Indeed, measurement of sexual female hormones revealed that the estradiol serum level was 4 times higher in transgenic mice Tg6 than in WT animals. While ovariectomy decreased VAH in WT females, this treatment restored VAH in Tg6 female mice. In line with this observation, injections of estradiol in ovariectomized Tg6 females dramatically reduced the VAH. We concluded that during chronic hypoxia, estradiol in carotid bodies suppresses the Epo-mediated elevation of ventilation. Considering the increased application of recombinant Epo for a variety of disorders, our data imply the need to take the patient's hormonal status into consideration.

Continuous Adaptation of Rats to Hypobaric Hypoxia Prevents Stressor Hyperglycemia and Optimizes Mitochondrial Respiration in Acute Hypoxia

2013 ◽  
Vol 4 (2) ◽  
pp. 137-147
Author(s):  
Vladimir I. Portnichenko ◽  
Valentina I. Nosar ◽  
Alla M. Sydorenko ◽  
Alla G. Portnychenko ◽  
Irina N. Mankovska
Keyword(s):  
Mitochondrial Respiration ◽  
Hypobaric Hypoxia ◽  
Acute Hypoxia

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)

Respiratory control in humans after 8 h of lowered arterial Po 2, hemodilution, or carboxyhemoglobinemia

2001 ◽  
Vol 90 (4) ◽  
pp. 1189-1195 ◽  
Author(s):  
Xiaohui Ren ◽  
Keith L. Dorrington ◽  
Peter A. Robbins
Keyword(s):  
Oxygen Content ◽  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Venous Blood ◽  
Respiratory Control ◽  
Progressive Increase ◽  
Arterial Oxygen ◽  
Hypoxic Ventilatory Response ◽  
Arterial Oxygen Content ◽  
End Tidal

In humans exposed to 8 h of isocapnic hypoxia, there is a progressive increase in ventilation that is associated with an increase in the ventilatory sensitivity to acute hypoxia. To determine the relative roles of lowered arterial Po 2 and oxygen content in generating these changes, the acute hypoxic ventilatory response was determined in 11 subjects after four 8-h exposures: 1) protocol IH (isocapnic hypoxia), in which end-tidal Po 2 was held at 55 Torr and end-tidal Pco 2 was maintained at the preexposure value; 2) protocol PB (phlebotomy), in which 500 ml of venous blood were withdrawn; 3) protocol CO, in which carboxyhemoglobin was maintained at 10% by controlled carbon monoxide inhalation; and 4) protocol C as a control. Both hypoxic sensitivity and ventilation in the absence of hypoxia increased significantly after protocol IH ( P < 0.001 and P < 0.005, respectively, ANOVA) but not after the other three protocols. This indicates that it is the reduction in arterial Po 2 that is primarily important in generating the increase in the acute hypoxic ventilatory response in prolonged hypoxia. The associated reduction in arterial oxygen content is unlikely to play an important role.

The Ventilatory Response in Severe Metabolic Acidosis

1976 ◽  
Vol 50 (5) ◽  
pp. 367-373 ◽  
Author(s):  
M. Fulop
Keyword(s):  
Metabolic Acidosis ◽  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Carbon Dioxide Tension ◽  
Pulmonary Insufficiency ◽  
Plasma Lactate ◽  
Severe Metabolic Acidosis ◽  
Arterial Blood ◽  
Blood Ph ◽  
Insufficient Time

1. The ventilatory response to severe metabolic acidosis was studied by measuring arterial blood carbon dioxide tension and pH in sixty-seven patients with blood pH < 7·10, none of whom had hypercapnia, pulmonary oedema, or chronic pulmonary insufficiency. The results were compared with those previously found in patients with uncomplicated diabetic ketoacidosis. 2. By that comparison, fifty-two of the sixty-seven patients with blood pH < 7·10 were judged to have ‘appropriate hypocapnia’, and fifteen had ‘submaximal hypocapnia’. Thirteen of the latter fifteen had circulatory failure and/or acute hypoxia, and seven of nine in whom it was measured had plasma lactate >9 mmol/l. 3. Hyperventilation was therefore usually well sustained in these patients with severe metabolic acidosis, except in most of those with acute tissue hypoxia. The latter may have had insufficient time to achieve maximum hyperventilation in response to their acidosis, or perhaps their submaximal hypercapnia presaged imminent failure of the hyperventilatory response.

scholarly journals Effects of Acute Hypoxia on Ventilatory Response at the Onset of Cycle Exercise in Man.

1992 ◽  
Vol 42 (5) ◽  
pp. 823-829 ◽  
Author(s):  
Miharu MIYAMURA ◽  
Koji ISHIDA ◽  
Tadashi KOBAYASHI ◽  
Tetsuo OHKUWA ◽  
Hiroshi ITOH
Keyword(s):  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Cycle Exercise

scholarly journals DL-3-n-Butylphthalide Improves Physical and Cognitive Performance of Animals with Acute and Chronic Hypobaric Hypoxia

2020 ◽  
Author(s):  
Gang Xu ◽  
Yikun Shi ◽  
Binda Sun ◽  
Lu Liu ◽  
Guoji E ◽  
...  
Keyword(s):  
Cognitive Functions ◽  
Hypobaric Hypoxia ◽  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
Redox Homeostasis ◽  
Oxidative Capacity ◽  
Treadmill Running ◽  
Escape Time ◽  
Physical Functions ◽  
Active Escape

Abstract Background: Studies revealed the protective effect of DL-3-n-butylphthalide (NBP) against ischemic hypoxia diseases. However, the role of NBP in animals with hypobaric hypoxia is elusive. This study investigated the effect of NBP on animals with acute and chronic hypobaric hypoxia.Methods: SD rats and Kunming mice administrated with NBP (90, 180 and 360 mg/kg for mice, and 60, 120, and 240 mg/kg for rats) were located in 10,000 m hypobaric hypoxia chamber. And survival analysis of animals implied that NBP could significantly improve survival percent at 30 min. Then, treated animals were evaluated for exhaustive time and exhaustive distance in forced exercise wheel-track treadmill and treadmill running experiments at 5,800 m for 3 or 21 days, to evaluate physical functions. Rats were also evaluated for times of active escape, average time of active escape, time of passive escape, and average time of passive escape in a shuttle-box experiment at 5,800 m for 7 or 28 days, to evaluate cognitive functions. ATP level was evaluated in the gastrocnemius muscle and maloaldehyde (MDA), superoxide dismutase (SOD), hydrogen peroxide (H2O2), lactate, and glutathione peroxiase (GSH-Px) measurements and routine blood tests were detected.Results: Exhaustive time for rats (NBP, 120 and 240 mg/kg) and exhaustive time and distance for mice (NBP, 90 mg/kg) significantly increased under acute hypoxia. And NBP treatment significantly increased the exhaustive time for rats under chronic hypoxia. Moreover, NBP of 120 and 240 mg/kg significantly increased the average time of passive escape under acute and chronic hypoxia. These results suggested that NBP could improve physical and cognitive functions under acute and chronic hypobaric hypoxia. Furthermore, the levels of MDA and H2O2 decreased but those of SOD and GSH-Px increased under acute and chronic hypoxia. Furthermore, the content of ATP significantly increased, while lactate level significantly decreased. The results presented that NBP could regulate redox homeostasis and improve energy metabolism.Conclusion: NBP could improve physical and cognitive functions under acute and chronic hypobaric hypoxia by increasing anti-oxidative capacity and energy supply.

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