Mechanisms of adrenomedullin-induced increase of pulmonary blood flow in fetal sheep

Pediatr Res. 1999 Feb;45(2):276-81. doi: 10.1203/00006450-199902000-00020.


Mechanisms of adrenomedullin-induced increases in fetal pulmonary blood flow were examined in 19 near-term fetal sheep using four key blocker drugs: nitric oxide synthase inhibitor (N(omega)-nitro-L-arginine), calcitonin gene-related peptide (CGRP) receptor blocker, ATP-dependent potassium (K(ATP)) channel blocker (glibenclamide), and cyclooxygenase inhibitor (indomethacin). Catheters were inserted into the left pulmonary artery and superior vena cava to administer drugs and into the main pulmonary and carotid arteries to measure pressures and heart rate. An ultrasonic flow transducer was placed around the left pulmonary artery to measure flow continuously. Adrenomedullin (mean 1.06 microg/kg) was injected into the left pulmonary artery before and after infusion of N(omega)-nitro-L-arginine (mean 96.5 mg/kg, n = 6), glibenclamide (mean 11.8 mg/kg, n = 6), CGRP receptor blocker (mean 312.0 microg/kg, n = 6), and indomethacin (mean 1.7 mg/kg, n = 8). Blockade was confirmed by appropriate agonist injection. The adrenomedullin-induced response in left pulmonary artery blood flow was inhibited by N(omega)-nitro-L-arginine (inhibition rate 99%) and significantly attenuated by glibenclamide (inhibition rate 44%); however, no significant changes were found with CGRP receptor blocker or indomethacin (inhibition rate 0 and 17%, respectively). The responses of the main pulmonary and carotid arterial pressures were similarly affected by those blockers. Our data suggest that in the fetal pulmonary circulation, the adrenomedullin-induced increase in pulmonary blood flow depends largely on nitric oxide release and partly on K(ATP) channel activation, and does not involve the CGRP receptor or a cyclooxygenase-mediated mechanism.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenomedullin
  • Animals
  • Calcitonin Gene-Related Peptide / pharmacology
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Cromakalim / pharmacology
  • Cyclooxygenase Inhibitors / pharmacology
  • Female
  • Fetus
  • Glyburide / pharmacology
  • Indomethacin / pharmacology
  • Lung / blood supply*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology*
  • Nitroarginine / pharmacology
  • Peptide Fragments / pharmacology
  • Peptides / pharmacology*
  • Peptides / physiology
  • Potassium Channel Blockers
  • Pregnancy
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / physiology*
  • Pulmonary Circulation / drug effects
  • Pulmonary Circulation / physiology*
  • Regional Blood Flow / drug effects
  • Sheep
  • Vasodilator Agents / pharmacology*


  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Cyclooxygenase Inhibitors
  • Peptide Fragments
  • Peptides
  • Potassium Channel Blockers
  • Vasodilator Agents
  • Cromakalim
  • calcitonin gene-related peptide (8-37)
  • Adrenomedullin
  • Nitroarginine
  • Calcitonin Gene-Related Peptide
  • Glyburide
  • Indomethacin