Skip to content

Centrally acting adrenomedullin in the long-term potentiation of sympathetic vasoconstrictor activity induced by intermittent hypoxia in rats

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)1371-1383
Number of pages13
JournalExperimental Physiology
Volume104
Issue number9
Early online date21 Jul 2019
DOIs
DateAccepted/In press - 17 Jul 2019
DateE-pub ahead of print - 21 Jul 2019
DatePublished (current) - 1 Sep 2019

Abstract

Adrenomedullin in the rostral ventrolateral medulla (RVLM) increases sympathetic activity; given that adrenomedullin is released during hypoxia, what are the effects of its agonism and antagonism in the RVLM after chronic intermitent hypoxia (CIH) exposure? What is the main finding and its importance? CIH exposure sensitizes adrenomedullin-dependent mechanisms in the RVLM, supporting its role as a sympathoexcitatory neuromodulator. A novel mechanism was identified for the generation of sympathetic overdrive and hypertension associated with hypoxia, providing potential guidance on new therapeutic approaches for controlling sympathetic hyperactivity in diseases such as sleep apnoea and neurogenic hypertension. Abstract: Adrenomedullin in the rostral ventrolateral medulla (RVLM) has been shown to increase sympathetic activity whereas the antagonism of its receptors inhibited this autonomic activity lowering blood pressure in conditions of hypertension. Given that hypoxia is a stimulant for releasing adrenomedullin, we hypothesized that the presence of this peptide in the RVLM associated with chronic intermittent hypoxia (CIH) would cause sympathetic overdrive. Juvenile male rats (50–55 g) submitted to CIH (6% oxygen every 9 min, 8 h day−1 for 10 days) were studied in an arterially perfused in situ preparation where sympathetic activity was recorded. In control rats (n = 6), exogenously applied adrenomedullin in the RVLM raised baseline sympathetic activity when combined with episodic activation of peripheral chemoreceptors (KCN 0.05%, 5 times every 5 min). This sympathoexcitatory response was markedly amplified in rats previously exposed to CIH (n = 6). The antagonism of adrenomedullin receptors in the RVLM caused a significant reduction in sympathetic activity in the CIH group (n = 7), but not in controls (n = 8). The transient reflex-evoked sympathoexcitatory response to peripheral chemoreceptor stimulation was not affected by either adrenomedullin or adrenomedullin receptor antagonism in the RVLM of control and CIH rats. Our findings indicate that CIH sensitizes the sympathoexcitatory networks within the RVLM to adrenomedullin, supporting its role as an excitatory neuromodulator when intermittent hypoxia is present. These data reveal novel state-dependent mechanistic insights into the generation of sympathetic overdrive and provide potential guidance on possible unique approaches for controlling sympathetic discharge in diseases such as sleep apnoea and neurogenic hypertension.

    Research areas

  • adrenomedullin, brainstem, hypertension, hypoxia, neuromodulation

Documents

Documents

  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Wiley at https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/EP087613. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 1 MB, PDF document

    Embargo ends: 21/07/20

    Request copy

    Licence: CC BY

DOI

View research connections

Related faculties, schools or groups