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Effects of A 2A and 5‐HT 2A Antagonists on Hypoxic and Hypercapnic Ventilatory Response in Rats Exposed to Chronic Sustained Hypoxia
Author(s) -
Moya Esteban A,
Powell Frank L
Publication year - 2016
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.30.1_supplement.1299.6
Subject(s) - ketanserin , hypoxic ventilatory response , hypoxia (environmental) , antagonist , ventilation (architecture) , chemistry , agonist , anesthesia , medicine , 5 ht receptor , endocrinology , serotonin , receptor , respiratory system , oxygen , mechanical engineering , organic chemistry , engineering
Different patterns and durations of hypoxic exposure cause different forms of plasticity in the neural control of ventilation (Pamenter & Powell, F1000Prime Rep, 5: 23, 2013). For example, acute intermittent hypoxia (AIH) causes long term facilitation (LTF) of ventilation and phrenic nerve activity, while chronic sustained hypoxia (CSH) causes ventilatory acclimatization to hypoxia (VAH). In both LTF and VAH, ventilation in normoxia is increased after the hypoxic stimulus is removed. Previous work has shown that 5HT 2a serotonin receptor activation (G q pathway) is necessary for LTF but not VAH. However, recent work (Nichols et al., J Appl Physiol, 112: 1678–1688, 2012) shows A 2A adenosine receptor activation (G s pathway) is also involved in LTF with more severe AIH (Pa O2 = 25–30 Torr vs. 35–45 Torr). We hypothesized that the G s pathway also contributes to VAH and tested this in adult male rats by blocking the G s and G q pathways before and after 7 days of CSH (PO 2 = 80 Torr) and measuring ventilation and the hypoxic ventilatory response (HVR) with barometric pressure plethysmography. Consistent with previous work, G q blockade with a 5HT 2a antagonist (Ketanserin, 1 mg/Kg i.p.) caused no significant changes before or after CSH. Gs blockade with an A 2A agonist antagonist (MSX‐3, 1mg/Kg i.p.) had no effect before CSH but after CSH it significantly increased ventilation in acute normoxia (1777±352 vs. 2396±268 ml/min*kg) and hypoxia (2063±195 vs. 2403±450 ml/min*kg). This contrasts with the effect of G s blockade during severe AIH to significantly decrease LTF and does not support our hypothesis. However, further experiments are necessary to determine the effects of blocking G s and G q pathways during CSH. Support or Funding Information NIH RO1 HL‐081823