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Related Experiment Videos

Decrease in arterial pressure induced by adrenomedullin in the hypothalamic paraventricular nucleus is mediated by

Yong Xu1, Teresa L Krukoff

  • 1Department of Cell Biology and Center for Neuroscience, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada T6G 2H7.

Regulatory Peptides
|April 20, 2004
PubMed
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Adrenomedullin (ADM) lowers blood pressure in the brain's PVN via nitric oxide (NO) and GABA. This effect involves neuronal and endothelial NO, but not inducible NO, in regulating mean arterial pressure (MAP).

Area of Science:

  • Neuroscience
  • Cardiovascular Physiology
  • Pharmacology

Background:

  • Adrenomedullin (ADM) is implicated in cardiovascular regulation.
  • The hypothalamic paraventricular nucleus (PVN) plays a key role in controlling blood pressure.
  • The precise mechanisms of ADM's action within the PVN are not fully understood.

Purpose of the Study:

  • To investigate the role of nitric oxide (NO) and GABA in mediating the hypotensive effects of ADM in the PVN.
  • To determine which isoforms of NO synthase (NOS) are involved in ADM's action.
  • To confirm the localization of ADM receptors in relation to NO-producing neurons in the PVN.

Main Methods:

  • Microinjections of ADM into the PVN of anesthetized rats.
  • Administration of NOS inhibitors (L-NAME, 7-NiNa, L-NIO, SMIT) and a GABA antagonist (bicuculline methiodide) prior to ADM.

Related Experiment Videos

  • Measurement of mean arterial pressure (MAP).
  • Combined NADPH-diaphorase histochemistry and in situ hybridization for ADM receptor component (RAMP2) in PVN sections.

    • Main Results:

    • ADM injection into the PVN significantly decreased MAP.
    • The hypotensive effect of ADM was attenuated by L-NAME, 7-NiNa, L-NIO, and bicuculline methiodide.
    • The selective inducible NOS inhibitor SMIT did not affect the ADM-induced decrease in MAP.
    • Double labeling confirmed the presence of ADM receptors on NO-producing neurons in both parvocellular and magnocellular PVN subdivisions.

    Conclusions:

    • The hypotensive effect of ADM in the PVN is mediated by both NO and GABA.
    • Neuronal NOS (nNOS) and endothelial NOS (eNOS) contribute to the NO-mediated hypotensive response.
    • ADM exerts its blood pressure-lowering effects in the PVN through a signaling pathway involving NO and GABA.