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The hypoxia‐induced facilitation of augmented breaths is prevented by the common action of carbonic anhydrase inhibitors
Author(s) -
Bell Harold James,
Haouzi Philippe A.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.799.30
Subject(s) - hyperventilation , acetazolamide , peripheral chemoreceptors , carbonic anhydrase , chemoreceptor , hypoxia (environmental) , facilitation , respiratory alkalosis , chemistry , apnea , anesthesia , endocrinology , medicine , pharmacology , oxygen , biochemistry , enzyme , metabolic acidosis , biology , neuroscience , receptor , organic chemistry
Hypoxia facilitates the generation of augmented breaths (ABs) in the breathing rhythm. Acetazolamide (Atz) treatment prevents this facilitation, likely by promoting CO 2 retention and counteracting hyperventilation‐induced alkalosis. However, Atz is also known to decrease the sensitivity of the arterial chemoreceptors. The question therefore remains as to whether Atz prevents the facilitation of ABs during hypoxia by offsetting the effects of respiratory alkalosis, or by suppressing peripheral chemoreceptor activity. In this study, we addressed this question by examining the effects of an alternative carbonic anhydrase inhibitor, methazolamide (Mtz), which has been reported to leave peripheral chemoreceptor sensitivity intact. Respiratory variables were monitored before, during and after two days of Mtz treatment (10 mg/kg i.p., bid) in unsedated and unrestrained adult male rats. Pre‐treatment, the number of ABs observed in a 5 minute observation window was 1.2 ± 0.8 and 17.4 ± 3.8 in room air and hypoxia, respectively. During Mtz treatment, the facilitation of ABs in hypoxia was rapidly and reversibly suppressed such that ABs we no longer significantly more frequent than they were in room air. The present results demonstrate that the hypoxia‐induced facilitation of ABs can be suppressed via the general effects of carbonic anhydrase inhibition, which are common to both Atz and Mtz.