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Related Experiment Videos

Adrenomedullin activity in chronically hypoxic rat lungs

L Zhao1, L A Brown, A A Owji

  • 1Department of Clinical Pharmacology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.

The American Journal of Physiology
|August 1, 1996
PubMed
Summary

Adrenomedullin (AM) effectively lowers pulmonary artery pressure in rats with hypoxia-induced pulmonary hypertension. This response is partly mediated by calcitonin gene-related peptide (CGRP) receptors, suggesting AM

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Area of Science:

  • Cardiovascular Physiology
  • Pulmonary Hypertension Research
  • Pharmacology

Background:

  • Adrenomedullin (AM) is a vasodilator structurally related to calcitonin gene-related peptide (CGRP).
  • Hypoxia-induced pulmonary hypertension is a significant clinical condition.
  • Understanding novel vasodilators' roles in pulmonary hypertension is crucial.

Purpose of the Study:

  • To investigate the activity of Adrenomedullin (AM) in the rat lung during hypoxia-induced pulmonary hypertension.
  • To explore the relationship between AM and CGRP pathways in regulating pulmonary artery pressure.
  • To assess the potential of AM as a therapeutic agent.

Main Methods:

  • Isolated perfused rat lung model ventilated with 2% oxygen.
  • Administration of varying doses of rat AM and alpha-CGRP.

Related Experiment Videos

  • Pretreatment with alpha-CGRP or CGRP antagonist (CGRP-(8-37)).
  • Measurement of pulmonary artery pressure.
  • Radioligand binding assays using 125I-labeled AM and 125I-labeled CGRP.
  • Quantification of lung immunoreactive AM and AM mRNA levels.

    • Main Results:

    • Both AM and alpha-CGRP dose-dependently reduced pulmonary artery pressure.
    • AM's hypotensive effect was partially attenuated by alpha-CGRP or CGRP antagonist, indicating CGRP receptor involvement.
    • 125I-labeled AM and CGRP binding increased significantly in lung membranes of hypoxic rats.
    • Hypoxic rats showed an enhanced hypotensive response to both AM and CGRP.
    • No significant changes were observed in lung immunoreactive AM concentrations or AM mRNA levels.

    Conclusions:

    • Adrenomedullin (AM) demonstrates significant vasodilatory activity in the context of hypoxia-induced pulmonary hypertension.
    • The response to AM is partly mediated through calcitonin gene-related peptide (CGRP) receptors.
    • AM shows potential for acute pharmacological management of pulmonary artery pressure in this condition.