Chronic intermittent hypoxia induces hypoxia-evoked catecholamine efflux in adult rat adrenal medulla via oxidative stress

Ganesh K. Kumar, Vandana Rai, Suresh D. Sharma, Devi Prasadh Ramakrishnan, Ying Jie Peng, Dangjai Souvannakitti, Nanduri R. Prabhakar

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Abstract

Chronic intermittent hypoxia (CIH) augments physiological responses to low partial pressures of O2 in the arterial blood. Adrenal medullae from adult rats, however, are insensitive to direct effects of acute hypoxia. In the present study, we examined whether CIH induces hypoxic sensitivity in the adult rat adrenal medulla and, if so, by what mechanism(s). Experiments were performed on adult male rats exposed to CIH (15s of 5% O2 followed by 5 min of 21% O2; 9 episodes h-1; 8 h d-1; for 3 or 10 days) or to comparable, cumulative durations of continuous hypoxia (CH; 4 h of 7% O2 followed by 20 h of 21% O2 for 1 or 10 days). Noradrenaline (NA) and adrenaline (ADR) effluxes were monitored from ex vivo adrenal medullae. In adrenal medullae of rats exposed to CIH, acute hypoxia evoked robust NA and ADR effluxes, whereas these responses were absent in control rats or in those exposed to CH for 1 or 10 days. Hypercapnia (10% CO2; either acidic, pH 6.8, or isohydric, pH 7.4) was ineffective in eliciting catecholamine (CA) efflux from control, CIH or CH rats. Nicotine (100 μm) evoked NA and ADR effluxes in control rats, and this response was abolished in CIH but not in CH rats. Systemic administration of 2-deoxyglucose depleted ADR content in control rats, and CIH attenuated this response, indicating downregulation of neurally regulated CA secretion. Cytosolic and mitochondrial aconitase enzyme activities decreased in CIH adrenal medullae, suggesting increased generation of superoxide anions. Systemic administration of antioxidants reversed the effect of CIH on the adrenal medulla. Rats exposed to CIH exhibited increased blood pressures and elevated plasma CA, and antioxidants abolished these responses. These observations demonstrate that CIH induces hypoxic sensing in the adult rat adrenal medulla via mechanisms involving increased generation of superoxide anions and suggest that hypoxia-evoked CA efflux from the adrenal medulla contributes, in part, to elevated blood pressure and plasma CA.

Original languageEnglish (US)
Pages (from-to)229-239
Number of pages11
JournalJournal of Physiology
Volume575
Issue number1
DOIs
StatePublished - Aug 1 2006

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Adrenal Medulla
Catecholamines
Oxidative Stress
Epinephrine
Norepinephrine
Hypoxia
Superoxides
Antioxidants
Aconitate Hydratase
Blood Pressure
Hypercapnia
Partial Pressure
Deoxyglucose
Nicotine

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Kumar, G. K., Rai, V., Sharma, S. D., Ramakrishnan, D. P., Peng, Y. J., Souvannakitti, D., & Prabhakar, N. R. (2006). Chronic intermittent hypoxia induces hypoxia-evoked catecholamine efflux in adult rat adrenal medulla via oxidative stress. Journal of Physiology, 575(1), 229-239. https://doi.org/10.1113/jphysiol.2006.112524
Kumar, Ganesh K. ; Rai, Vandana ; Sharma, Suresh D. ; Ramakrishnan, Devi Prasadh ; Peng, Ying Jie ; Souvannakitti, Dangjai ; Prabhakar, Nanduri R. / Chronic intermittent hypoxia induces hypoxia-evoked catecholamine efflux in adult rat adrenal medulla via oxidative stress. In: Journal of Physiology. 2006 ; Vol. 575, No. 1. pp. 229-239.
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abstract = "Chronic intermittent hypoxia (CIH) augments physiological responses to low partial pressures of O2 in the arterial blood. Adrenal medullae from adult rats, however, are insensitive to direct effects of acute hypoxia. In the present study, we examined whether CIH induces hypoxic sensitivity in the adult rat adrenal medulla and, if so, by what mechanism(s). Experiments were performed on adult male rats exposed to CIH (15s of 5{\%} O2 followed by 5 min of 21{\%} O2; 9 episodes h-1; 8 h d-1; for 3 or 10 days) or to comparable, cumulative durations of continuous hypoxia (CH; 4 h of 7{\%} O2 followed by 20 h of 21{\%} O2 for 1 or 10 days). Noradrenaline (NA) and adrenaline (ADR) effluxes were monitored from ex vivo adrenal medullae. In adrenal medullae of rats exposed to CIH, acute hypoxia evoked robust NA and ADR effluxes, whereas these responses were absent in control rats or in those exposed to CH for 1 or 10 days. Hypercapnia (10{\%} CO2; either acidic, pH 6.8, or isohydric, pH 7.4) was ineffective in eliciting catecholamine (CA) efflux from control, CIH or CH rats. Nicotine (100 μm) evoked NA and ADR effluxes in control rats, and this response was abolished in CIH but not in CH rats. Systemic administration of 2-deoxyglucose depleted ADR content in control rats, and CIH attenuated this response, indicating downregulation of neurally regulated CA secretion. Cytosolic and mitochondrial aconitase enzyme activities decreased in CIH adrenal medullae, suggesting increased generation of superoxide anions. Systemic administration of antioxidants reversed the effect of CIH on the adrenal medulla. Rats exposed to CIH exhibited increased blood pressures and elevated plasma CA, and antioxidants abolished these responses. These observations demonstrate that CIH induces hypoxic sensing in the adult rat adrenal medulla via mechanisms involving increased generation of superoxide anions and suggest that hypoxia-evoked CA efflux from the adrenal medulla contributes, in part, to elevated blood pressure and plasma CA.",
author = "Kumar, {Ganesh K.} and Vandana Rai and Sharma, {Suresh D.} and Ramakrishnan, {Devi Prasadh} and Peng, {Ying Jie} and Dangjai Souvannakitti and Prabhakar, {Nanduri R.}",
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Kumar, GK, Rai, V, Sharma, SD, Ramakrishnan, DP, Peng, YJ, Souvannakitti, D & Prabhakar, NR 2006, 'Chronic intermittent hypoxia induces hypoxia-evoked catecholamine efflux in adult rat adrenal medulla via oxidative stress', Journal of Physiology, vol. 575, no. 1, pp. 229-239. https://doi.org/10.1113/jphysiol.2006.112524

Chronic intermittent hypoxia induces hypoxia-evoked catecholamine efflux in adult rat adrenal medulla via oxidative stress. / Kumar, Ganesh K.; Rai, Vandana; Sharma, Suresh D.; Ramakrishnan, Devi Prasadh; Peng, Ying Jie; Souvannakitti, Dangjai; Prabhakar, Nanduri R.

In: Journal of Physiology, Vol. 575, No. 1, 01.08.2006, p. 229-239.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Chronic intermittent hypoxia induces hypoxia-evoked catecholamine efflux in adult rat adrenal medulla via oxidative stress

AU - Kumar, Ganesh K.

AU - Rai, Vandana

AU - Sharma, Suresh D.

AU - Ramakrishnan, Devi Prasadh

AU - Peng, Ying Jie

AU - Souvannakitti, Dangjai

AU - Prabhakar, Nanduri R.

PY - 2006/8/1

Y1 - 2006/8/1

N2 - Chronic intermittent hypoxia (CIH) augments physiological responses to low partial pressures of O2 in the arterial blood. Adrenal medullae from adult rats, however, are insensitive to direct effects of acute hypoxia. In the present study, we examined whether CIH induces hypoxic sensitivity in the adult rat adrenal medulla and, if so, by what mechanism(s). Experiments were performed on adult male rats exposed to CIH (15s of 5% O2 followed by 5 min of 21% O2; 9 episodes h-1; 8 h d-1; for 3 or 10 days) or to comparable, cumulative durations of continuous hypoxia (CH; 4 h of 7% O2 followed by 20 h of 21% O2 for 1 or 10 days). Noradrenaline (NA) and adrenaline (ADR) effluxes were monitored from ex vivo adrenal medullae. In adrenal medullae of rats exposed to CIH, acute hypoxia evoked robust NA and ADR effluxes, whereas these responses were absent in control rats or in those exposed to CH for 1 or 10 days. Hypercapnia (10% CO2; either acidic, pH 6.8, or isohydric, pH 7.4) was ineffective in eliciting catecholamine (CA) efflux from control, CIH or CH rats. Nicotine (100 μm) evoked NA and ADR effluxes in control rats, and this response was abolished in CIH but not in CH rats. Systemic administration of 2-deoxyglucose depleted ADR content in control rats, and CIH attenuated this response, indicating downregulation of neurally regulated CA secretion. Cytosolic and mitochondrial aconitase enzyme activities decreased in CIH adrenal medullae, suggesting increased generation of superoxide anions. Systemic administration of antioxidants reversed the effect of CIH on the adrenal medulla. Rats exposed to CIH exhibited increased blood pressures and elevated plasma CA, and antioxidants abolished these responses. These observations demonstrate that CIH induces hypoxic sensing in the adult rat adrenal medulla via mechanisms involving increased generation of superoxide anions and suggest that hypoxia-evoked CA efflux from the adrenal medulla contributes, in part, to elevated blood pressure and plasma CA.

AB - Chronic intermittent hypoxia (CIH) augments physiological responses to low partial pressures of O2 in the arterial blood. Adrenal medullae from adult rats, however, are insensitive to direct effects of acute hypoxia. In the present study, we examined whether CIH induces hypoxic sensitivity in the adult rat adrenal medulla and, if so, by what mechanism(s). Experiments were performed on adult male rats exposed to CIH (15s of 5% O2 followed by 5 min of 21% O2; 9 episodes h-1; 8 h d-1; for 3 or 10 days) or to comparable, cumulative durations of continuous hypoxia (CH; 4 h of 7% O2 followed by 20 h of 21% O2 for 1 or 10 days). Noradrenaline (NA) and adrenaline (ADR) effluxes were monitored from ex vivo adrenal medullae. In adrenal medullae of rats exposed to CIH, acute hypoxia evoked robust NA and ADR effluxes, whereas these responses were absent in control rats or in those exposed to CH for 1 or 10 days. Hypercapnia (10% CO2; either acidic, pH 6.8, or isohydric, pH 7.4) was ineffective in eliciting catecholamine (CA) efflux from control, CIH or CH rats. Nicotine (100 μm) evoked NA and ADR effluxes in control rats, and this response was abolished in CIH but not in CH rats. Systemic administration of 2-deoxyglucose depleted ADR content in control rats, and CIH attenuated this response, indicating downregulation of neurally regulated CA secretion. Cytosolic and mitochondrial aconitase enzyme activities decreased in CIH adrenal medullae, suggesting increased generation of superoxide anions. Systemic administration of antioxidants reversed the effect of CIH on the adrenal medulla. Rats exposed to CIH exhibited increased blood pressures and elevated plasma CA, and antioxidants abolished these responses. These observations demonstrate that CIH induces hypoxic sensing in the adult rat adrenal medulla via mechanisms involving increased generation of superoxide anions and suggest that hypoxia-evoked CA efflux from the adrenal medulla contributes, in part, to elevated blood pressure and plasma CA.

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