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Received April 28, 2006
Revised May 25, 2006
Accepted after revision June 14, 2006
1 Case Western Reserve University
* To whom correspondence should be addressed. E-mail: kgk{at}po.cwru.edu.
Chronic intermittent hypoxia (CIH) augments physiological responses to low pO2. Adrenal medullae from adult rats, however, are insensitive to direct effect 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 (15 s of 5% O2 followed by 5 min of 21% O2; 9 episodes/h; 8h/d; for 3 days or 10 days) or to comparable, cumulative duration of continuous hypoxia (CH; 4 h of 7% O2 followed by 20 h of 21% O2 for 1 day or 10 days). Norepinephrine (NE) and epinephrine (EPI) effluxes were monitored from ex vivo adrenal medullae. In CIH adrenal medulla, acute hypoxia evoked robust NE and EPI effluxes whereas these responses were absent in control or 1 day or 10 days CH exposed rats. Hypercapnia (10% CO2; either acidic, pH 6.8 or isohydric, pH 7.4) was ineffective in eliciting catecholamine (CA) efflux from control or CIH or CH rats. Nicotine (100 µM) evoked NE and EPI effluxes in controls and this response was abolished in CIH but not in CH rats. Systemic administration of 2-deoxyglucose depleted EPI content in control rats and CIH attenuated this response indicating down-regulation of neurally regulated CA secretion. Cytosolic and mitochondrial aconitase enzyme activities decreased in CIH adrenal medullae suggesting increased generation of O2.-. Systemic administration of antioxidants reversed the effect of CIH on adrenal medulla. CIH exposed rats 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 O2.- and suggest that hypoxia-evoked CA efflux from adrenal medulla contributes, in part, to elevated blood pressure and plasma CA.
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