Effect of intermedin/adrenomedullin2 on the pulmonary vascular bed in hypoxia-induced pulmonary hypertensive rats

Life Sci. 2018 Jan 1;192:62-67. doi: 10.1016/j.lfs.2017.11.031. Epub 2017 Nov 21.


Aims: This study aimed to investigate the effect and mechanism of action of intermedin/adrenomedullin2 (IMD/AM2) on the pulmonary vascular bed in pulmonary hypertensive rats.

Materials and methods: Male Sprague-Dawley rats were exposed to hypobaric hypoxia for 3 weeks to induce pulmonary hypertension (PHT). The development of PHT was confirmed by histopathological analyses and measurement of hematocrit, basal perfusion pressure, and right ventricle hypertrophy. Subsequently, the effect of IMD/AM2 in pulmonary hypertensive rats was assessed with both, isolated organ bath and isolated lung perfusion studies.

Key findings: In the PHT group, the basal perfusion pressure and % hematocrit were increased, and right ventricle hypertrophy occurred after 3 weeks of hypoxia exposure. Increased medial wall thickness was also observed in the pulmonary artery with histopathological analysis. In the PHT, the nitric oxide-mediated vasodilation caused by IMD/AM2 in the pulmonary vascular bed and this was as potent as the control group. Acetylcholine responses were also protected in pulmonary hypertensive rats.

Significance: Our results showed for the first time in in vitro studies that IMD/AM2 administration causes potent, concentration-dependent vasodilation in the main and resistance pulmonary arteries of rats with PHT. Based on these results, IMD/AM2 might be considered as a future therapeutic target for PHT treatment.

Keywords: Hypoxia-induced pulmonary hypertension; Intermedin/adrenomedullin(2); Isolated rat lung; Pulmonary artery.

MeSH terms

  • Acetylcholine / pharmacology
  • Adrenomedullin / therapeutic use*
  • Animals
  • Blood Pressure
  • Hematocrit
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Hypertrophy, Right Ventricular / drug therapy
  • Hypertrophy, Right Ventricular / physiopathology
  • Hypoxia / physiopathology
  • In Vitro Techniques
  • Male
  • Neuropeptides / therapeutic use*
  • Nitric Oxide / pharmacology
  • Pulmonary Artery / drug effects
  • Pulmonary Circulation / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Vasodilator Agents / therapeutic use*


  • Adm2 protein, rat
  • Neuropeptides
  • Vasodilator Agents
  • Adrenomedullin
  • Nitric Oxide
  • Acetylcholine