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Phrenic long‐term facilitation is induced by acute intermittent hypoxia despite systemic ATP receptor antagonist attenuation of hypoxic phrenic response in rats
Author(s) -
Sibigtroth Christine Marie,
Mitchell Gordon S.
Publication year - 2008
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.22.1_supplement.1232.10
Subject(s) - phrenic nerve , intermittent hypoxia , hypoxia (environmental) , anesthesia , medicine , respiratory system , ppads , hypoxic ventilatory response , receptor , antagonist , pharmacology , chemistry , oxygen , organic chemistry , obstructive sleep apnea
Phrenic long‐term facilitation (pLTF) is a form of respiratory plasticity induced by acute intermittent hypoxia (AIH; Mitchell et al., 2001). Although pLTF is elicited in carotid denervated rats, its magnitude is reduced in proportion to the reduction of the hypoxic phrenic response (~35% normal; Bavis and Mitchell, 2002). Thus, the role of residual chemosensory afferent activity and hypoxic phrenic responses in pLTF induction remains unclear. Since ATP is necessary for hypoxic stimulation of carotid chemoafferent activity and the hypoxic ventilatory response (Rong et al., 2003), we tested the hypothesis that systemic P2X receptor antagonism would block both the hypoxic phrenic response and pLTF following AIH in anesthetized rats. Pyridoxal‐phosphate‐6‐azophenyl‐2',4'‐disulfonic acid (PPADS; 100 mg/kg IV), a non‐selective P2X receptor antagonist, was administered to anesthetized, vagotomized, paralyzed and ventilated male Sprague‐Dawley rats prior to AIH (3, 5‐min episodes of 10% O2; 5 min intervals). Although PPADS strongly attenuated the hypoxic phrenic amplitude response (3 ± 5% baseline), significant pLTF was observed in phrenic burst amplitude 60 min post‐AIH (34±8% baseline, n=4; p < 0.05). Thus, AIH initiates mechanisms of pLTF independently from the hypoxic phrenic response and, presumably, chemoafferent neuron activation. Supported by: NIH HL80209 and T32RR17503