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Adrenomedullin in the treatment of pulmonary hypertension
  1. Department of Surgery
  2. Indiana University School of Medicine
  3. Indianapolis, IN 46202, USA

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Pulmonary hypertension is seen in patients in whom there is an increased pulmonary pressure (systolic pulmonary/systemic arterial pressure > 60%; > 15–20 mm Hg). The disease slowly progresses, applying stress on the right heart function leading to heart failure and death. Although the precise mechanism of development of precapillary pulmonary hypertension remains to be defined, understanding of the local factors that control pulmonary vascular tone and structure has increased greatly in the past decade. It is known that the endothelium releases several potent vasoactive mediators, including endothelin-1, prostacyclin, and endothelium derived relaxing factor, nitric oxide (NO). Decreased production of nitric oxide and prostacyclin, and increased release of endothelin, have been shown to promote pulmonary vasoconstriction resulting in pulmonary hypertension.1 The vascular endothelium expresses receptors for ligands that play an important role in maintaining pulmonary vascular tone.2

Adrenomedullin: a hypotensive agent

Adrenomedullin, a peptide with a molecular weight of 6047 daltons first isolated from human phaeochromocytoma cells, has been shown to have a fast acting and long lasting hypotensive effect. Human adrenomedullin consists of 52 amino acids, and is a member of the calcitonin gene related protein superfamily.3 It is present in high concentrations in the right atrium of the heart, where it reaches a 5 to 50-fold excess over the concentrations found in the left atrium and the ventricles, respectively, and also in several organs. In intact anaesthetised rats, a 1 nmol/kg dose of human adrenomedullin administered intravenously over 15 seconds resulted in an average fall …

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