Effects of centrally administered vasostatin I on the modulation of cardio-respiratory function and sympathetic reflexes

Ahmed A. Rahman, Israt Z. Shahid, Angelina Y. Fong, Paul M. Pilowsky

    Research output: Contribution to journalMeeting abstract

    Abstract

    Vasostatin I (CgA₁₋₇₆) is a naturally occurring and biologically active N-terminal peptide derived from chromogranin A (CgA) and is so named for its inhibitory effects on vascular tension. Recently vasostatins have been reported to exert a negative inotropic effect and counteract the β-adrenergic positive inotropic effect on isolated heart preparation of frog, eel and rat. CgA mRNA is frequently expressed in the rostral ventrolateral medulla (RVLM) including bulbospinal catecholaminergic neurons. CgA microinjection into RVLM showed inhibitory effects on blood pressure (BP), heart rate (HR) and sympathetic nerve activity (SNA) and proteolytic fragments of CgA were suggested to be responsible for that effect. We hypothesized vasostatin I might be the fragment responsible for the central effects of CgA. The effects of vasostatin I (CgA₁₇₋₇₆) (VS-I) delivered by intrathecal injection and direct microinjection into the RVLM on cardiorespiratory function in urethane anesthetized, vagotomised, mechanically ventilated Sprague-Dawley rats (n=21) were evaluated. The effects of intrathecal VS-I on somato-sympathetic, baroreceptor and peripheral chemoreceptor reflexes were also examined. At the concentration used (10, 100 or 200 μM for intrathecal or 5 μM for microinjection) VS-I produced no significant change in mean arterial pressure, HR, splanchnic SNA, phrenic nerve amplitude or phrenic nerve frequency. Somato-sympathetic, baroreceptor and peripheral chemoreceptor reflexes were unchanged following intrathecal VS-I. Our results indicate that vasostatin I is not the active proteolytic CgA fragment and may not be a central modulator of cardio-respiratory function and physiological reflexes.
    Original languageEnglish
    Pages (from-to)123
    Number of pages1
    JournalHypertension
    Volume58
    Issue number1
    Publication statusPublished - 2011
    EventAnnual Scientific Meeting of the High Blood Pressure Research Council of Australia (32nd : 2010) - Melbourne
    Duration: 1 Dec 20103 Dec 2010

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