Peng, Ying-Jie, and Nanduri R. Prabhakar. Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory activity. 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

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... paradigms of CIH for 10 days: 1) multiple exposures to short durations of intermittent hypoxia per day (SDIH; 15 s of 5% O2 ϩ 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) ϩ 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 O 2 Ϫ ⅐ radical scavenger prevented SDIHinduced 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 O 2 Ϫ ⅐ radicals play an important role in SDIH-induced sensitization of the carotid body. hypoxic sensitivity; superoxide anions; oxidative stress CHRONIC INTERMITTENT HYPOXIA (CIH) is encountered under many physiological and pathophysiological situations (15). Reported responses to CIH in experimental animals include increased blood pressure (3), augmented sympathetic nerve activity (7), elevated circulating catecholamines (1), enhanced long-term facilitation (LTF) of the respiratory motor activity (9, 11, 14) , and augmented ventilatory response to hypoxia (9). Rats in which carotid bodies have been denervated show no increase in blood pressure as well as augmented sympathetic nerve activity in response to CIH (3). Enhanced hypoxic ventilatory response in animals exposed to CIH can be mimicked with electrical stimulations of the carotid sinus nerves (9). These studies led to the suggestion that cardiorespiratory changes in response to CIH are mediated in part from aug-