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Effects of A 2 a Receptors on the Hypoxic Ventilatory Response in Rats Exposed to Chronic Sustained Hypoxia
Author(s) -
Basaran K,
Moya Esteban,
Fu Zengxing,
Powell Frank
Publication year - 2015
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.29.1_supplement.659.2
Subject(s) - hypoxic ventilatory response , hypercapnia , hypoxia (environmental) , ventilation (architecture) , adenosine receptor , adenosine , anesthesia , medicine , intermittent hypoxia , phrenic nerve , antagonist , endocrinology , chemistry , pharmacology , receptor , agonist , respiratory system , oxygen , obstructive sleep apnea , mechanical engineering , organic chemistry , engineering
Recent studies show that long term facilitation of phrenic nerve activity (LTF) with acute intermittent hypoxia (IH) involves two signaling pathways. In addition to the well‐known serotonergic (Gq) pathway, a Gs pathway can be activated by adenosine receptor 2 (A 2 a) agonists and cause LTF without IH (J Neurosci 28:2033‐42, 2008). Gs can inhibit the Gq pathway as A 2 a antagonists increase LTF from IH by disinhibiting Gq (J Physiol 588:255‐66, 2010). We tested the hypothesis that Gs also contributes to plasticity in ventilatory control during chronic sustained hypoxia (CH) by measuring the effects of A2a antagonists and agonists on ventilatory responses to hypoxia and hypercapnia in adult male rats before and after one week of CH (P O2 = 80 Torr in a hypobaric chamber). Ventilation measured in awake unrestrained rats with barometric pressure plethysmography increased after CH; acute ventilatory responses to hypoxia or hypercapnia increased also. Acute administration of A 2 a antagonist (MSX‐3, 1 mg/Kg i.p.) after CH did not change ventilation or acute ventilatory responses. A 2 a agonists (CGS 21680, 100 µg/Kg i.p.) before CH had no effect on ventilation or ventilatory responses, in contrast to stimulation reported for sleeping rats (J Neurosci 28:2033‐42, 2008). The results do not support a role for Gs in the increased ventilatory drive and hypoxic responses with CH, in contrast to their role in LTF in IH. Supported by NIH RO1 HL‐081823.