Journal of Applied Physiology
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J Appl Physiol 96: 1236-1242, 2004. First published December 5, 2003; doi:10.1152/japplphysiol.00820.2003
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HIGHLIGHTED TOPICS
Oxygen Sensing in Health and Disease

Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory activity

Ying-Jie Peng and Nanduri R. Prabhakar

Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106

Submitted 1 August 2003 ; accepted in final form 4 December 2003

Reflexes arising from the carotid bodies may play an important role in cardiorespiratory changes evoked by chronic intermittent hypoxia (CIH). In the present study, we examined whether CIH affects the hypoxic sensing ability of the carotid bodies and, if so, by what mechanisms. Experiments were performed on adult male rats (Sprague-Dawley, 250–300 g) exposed to two paradigms of CIH for 10 days: 1) multiple exposures to short durations of intermittent hypoxia per day (SDIH; 15sof5%O2 + 5 min of 21% O2, 9 episodes/h, 8 h/day) and 2) single exposure to longer durations of intermittent hypoxia per day [LDIH; 4 h of hypobaric hypoxia (0.4 atm/day) + 20 h of normoxia]. Carotid body sensory response to graded isocapnic hypoxia was examined in both groups of animals under anesthetized conditions. Hypoxic sensory response was significantly enhanced in SDIH but not in LDIH animals. Similar enhancement in hypoxic sensory response was also elicited in ex vivo carotid bodies from SDIH animals, suggesting that the effects were not secondary to cardiovascular changes. SDIH, however, had no significant effect on the hypercapnic sensory response. The effects of SDIH on the hypoxic sensory response completely reversed after SDIH animals were placed in a normoxic environment for an additional 10 days. Previous treatment with systemic administration of radical scavenger prevented SDIH-induced augmentation of the hypoxic sensory response. These results demonstrate that SDIH but not LDIH results in selective augmentation of the hypoxic response of the carotid body and radicals play an important role in SDIH-induced sensitization of the carotid body.

hypoxic sensitivity; superoxide anions; oxidative stress


Address for reprint requests and other correspondence: N. R. Prabhakar, Dept. of Physiology & Biophysics, School of Medicine, Case Western Reserve Univ., 10900 Euclid Ave., Cleveland, OH 44106 (E-mail: nrp{at}po.cwru.edu).




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