Acute intermittent hypoxia induced long-term facilitation of sympathetic nerve activity is serotonin dependent

T. Xing, T. G. Bautista, A. Y. Fong, P. M. Pilowsky

    Research output: Contribution to journalMeeting abstract

    Abstract

    Acute intermittent hypoxia (AIH) is a frequently studied experimental model of obstructive sleep apnoea (OSA). AIH can elicit a long-term increase in sympathetic outflow (long-term facilitation, LTF), however the underlying mechanism is not clear. In this study, we aimed to investigate the role of serotonin in the development of sympathetic LTF. In urethane-anaesthetized, vagotomised and mechanically ventilated Sprague-Dawley rats, we investigated the effect of ten 45s episodes of 10% O2-90% N2 on splanchnic sympathetic nerve activity (sSNA), and the hypoxic sympathetic chemoreceptor and baroreceptor reflex 60 mins after AIH. AIH elicited a robust increase in sSNA (+56.1±7%; n=10, P<0.001) compared with time controls (rats not exposed to hypoxia, n=5) 60 min after the end of AIH. After the establishment of sympathetic LTF, the hypoxic chemoreceptor reflex was enhanced (peak change from 92±22 vs. 186±38%; baseline vs. after AIH, P<0.05), and the sympathetic baroreceptor reflex sensitivity was increased (Gainmax from 1.79±0.18 to 2.60±0.28%mm Hg-1; n=8, P<0.05). Pre-treatment with systemic methysergide (4mg/kg, i.v., N=8), a broad spectrum serotonin receptor antagonist, attenuated the AIH induced LTF of sSNA (+20.1±7.6%; P>0.05 compared with time controls). However, the enhancement of hypoxic sympathetic chemoreceptor reflex 60 mins after AIH was unaffected by methysergide pre-treatment (peak change from 150±41 to 231±57%; baseline vs. after AIH, P<0.05), while the increase in sympathetic baroreceptor reflex sensitivity was abolished (Gainmax from 3.16±0.71 to 2.32±0.50%mm Hg-1; n=6, P>0.05) Our findings indicate that the AIH-induced sympathetic LTF requires 5-HT receptors, however, the enhancement of the hypoxic sympathetic chemoreflex is likely mediated by non-serotoninergic mechanisms.
    Original languageEnglish
    Pages (from-to)502
    Number of pages1
    JournalHypertension
    Volume60
    Issue number2
    Publication statusPublished - 2012
    EventAnnual Scientific Meeting of the High Blood Pressure Research Council of Australia (33rd : 2011) - Perth
    Duration: 6 Dec 20119 Dec 2011

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