Neuromedin U causes biphasic effects on sympathetic vasomotor tone and increases respiratory drive in rat rostral ventrolateral medulla

Ahmed A. Rahman, Israt Z. Shahid, Paul M. Pilowsky

    Research output: Contribution to journalMeeting abstract

    Abstract

    The rostral ventrolateral medulla (RVLM) is the key nucleus for controlling sympathetic vasomotor outflow and also essential for the integration of sympathetic reflexes. Neuromedin U (NMU), a hypothalamic neuropeptide, increases blood pressure and sympathetic nerve activity (SNA) when injected intracerebroventricularly. However, the central areas that mediate these cardiovascular effects are unknown. The present study was conducted in urethaneanaesthetized, vagotomised and artificially ventilated male Sprague-Dawley rats (n=16) to investigate the effects of bilateral microinjection of NMU into RVLM on cardiorespiratory variables. Microinjection of NMU into RVLM elicited a pressor response, tachycardia, and an increase in splanchnic SNA (SSNA) and lumbar SNA (LSNA) at lower doses (25 and 50 pmol). At a higher dose (100 pmol), NMU caused a biphasic response, a brief hypertension and sympathoexcitation followed by a prolonged hypotension and sympathoinhibition. The peak excitatory and inhibitory response was found at 100 pmol NMU with an increase in MAP, HR, SSNA and LSNA of 36 mm Hg, 20 bpm, 34% and 89%, respectively, and a decrease of 33 mm Hg, 25 bpm, 42% and 52%, respectively, from baseline. NMU, in the RVLM, also increased phrenic nerve amplitude, expiratory period, and reduced inspiratory period. The AUC of inspiratory (I-) peak of both SSNA and LSNA are potentiated at the excitatory phase of NMU response in the RVLM, but at inhibitory phase the I-peak of both SNA are reduced. On the other hand, the AUC of post-inspiratory peak of both SSNA and LSNA is reduced at excitatory as well as inhibitory phase of NMU effect. The present study provides functional evidence for a complex differential modulatory activity of NMU on the cardiovascular and respiratory responses that are integrated in the RVLM.
    Original languageEnglish
    Pages (from-to)495
    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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