Influence of inhaled iloprost on transpulmonary gradient of big endothelin in patients with pulmonary hypertension

Circulation. 2003 Mar 25;107(11):1509-13. doi: 10.1161/01.cir.0000056104.49686.4b.

Abstract

Background: The pulmonary circulation is an important site for the production and clearance of endothelin (ET)-1, a potent vasoactive and mitogenic peptide. In healthy individuals, 40% to 50% of circulating ET-1 is removed on each passage through the lungs resulting in an arteriovenous ratio of <1, whereas many patients with pulmonary arterial hypertension (PAH) have ratios >1, indicating reduced clearance or increased release of endothelin. The influence of inhaled prostanoids on endothelin clearance is unknown.

Methods and results: In a prospective investigation, plasma concentrations of big endothelin-1 (big ET-1, Elisa) were measured in 15 patients with pulmonary hypertension undergoing right heart catheterization with iloprost inhalation (4 m, 11 f, aged 35 to 75 years, mean pulmonary arterial pressure (PAPm) 54+/-2.3 mm Hg, pulmonary vascular resistance (PVR) 1061+/-141 dyn x sec x cm(-5)). There was a significant transpulmonary gradient for big ET-1 with 31% +/-11% higher concentrations in the radial artery than in the pulmonary artery (P<0.001). After inhalation of iloprost a significant decrease in the AV-ratio from 1.31+/-0.11 to 0.92+/-0.06 (P<0.007) was observed. The pulmonary net release of 3.10+/-0.65 pmol/min big ET-1 at baseline decreased to -1.24+/-1.32 pmol/min (P=0.013) within 15 minutes indicating a restored balance. Patients under long-term treatment with iloprost (n=7) tended to have a lower net release and AV-ratio for big ET-1 than patients without pretreatment.

Conclusion: An increase in pulmonary clearance of big-ET could be a mechanism contributing to the beneficial effects of inhaled prostanoids in the treatment of PAH.

Publication types

  • Case Reports
  • Clinical Trial

MeSH terms

  • Administration, Inhalation
  • Adult
  • Aged
  • Endothelin-1
  • Endothelins / blood*
  • Female
  • Hemodynamics / drug effects
  • Humans
  • Hypertension, Pulmonary / blood
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Iloprost / administration & dosage
  • Iloprost / pharmacology*
  • Iloprost / therapeutic use
  • Male
  • Middle Aged
  • Protein Precursors / blood*
  • Pulmonary Circulation / drug effects

Substances

  • Endothelin-1
  • Endothelins
  • Protein Precursors
  • Iloprost