Adrenomedullin activity in chronically hypoxic rat lungs

Am J Physiol. 1996 Aug;271(2 Pt 2):H622-9. doi: 10.1152/ajpheart.1996.271.2.H622.


Adrenomedullin (AM) is a novel vasodilator with structural similarities to calcitonin gene-related peptide (CGRP). This study investigated AM activity in the rat lung during hypoxia-induced pulmonary hypertension. Both rat AM (0.2-10 nmol) and alpha-CGRP (0.2-2 nmol) produced dose-related reductions in pulmonary artery pressure in the isolated perfused lung ventilated with 2% O2. Pretreatment with alpha-CGRP, which demonstrated tachyphylaxis, or its antagonist, CGRP-(8-37), reduced the hypotensive response to AM, suggesting that part of the response to AM is mediated by CGRP receptors. 125I-labeled AM and 125I-labeled CGRP binding was significantly increased in lung membranes from 7-day hypoxic animals (AM from 1.94 +/- 0.3 to 3.36 +/- 0.4 and CGRP from 0.06 +/- 0.01 to 0.12 +/- 0.02 pmol/mg protein), with no change in dissociation constant. Moreover, the hypotensive response to both peptides was increased in the lungs of 7-day hypoxic rats. There was no significant change in lung immunoreactive AM concentrations (hypoxic 5.04 +/- 0.48 vs. control 6.28 +/- 0.76 pmol/g wet wt of tissue) or steady-state AM mRNA levels in 7-day hypoxic rats. Nonetheless, AM may be useful for the acute pharmacological manipulation of pulmonary artery pressure in hypoxia-induced pulmonary hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin
  • Animals
  • Base Sequence
  • Chronic Disease
  • Hypertension, Pulmonary / metabolism
  • Hypoxia / metabolism*
  • Lung / metabolism*
  • Molecular Sequence Data
  • Peptides / metabolism*
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Reference Values
  • Vasodilator Agents / metabolism


  • Peptides
  • RNA, Messenger
  • Vasodilator Agents
  • Adrenomedullin