Inhaled iloprost reverses vascular remodeling in chronic experimental pulmonary hypertension.

Abstract

RATIONALE:

Inhaled iloprost is an effective therapy for pulmonary arterial hypertension (PAH). However, no study to date has addressed the effects of inhaled iloprost on changes to pulmonary vascular structure that occur in PAH.

OBJECTIVES:

The present study was designed to investigate chronic antiremodeling effects of inhaled iloprost in monocrotaline (MCT)-induced PAH in rats.

METHODS:

Four weeks after a single injection of MCT, after full establishment of PAH, rats were nebulized with iloprost at a dose of 6 microg . kg(-1) . day(-1), or underwent sham nebulization with saline.

RESULTS:

After 2 weeks of inhalation therapy, right ventricular pressure and pulmonary vascular resistance were reversed in rats treated with iloprost, but not in sham-treated control animals. Systemic arterial pressure was unaffected. In addition, right heart hypertrophy, the degree of pulmonary artery muscularization, and the medial wall thickness of intraacinar pulmonary arteries regressed in response to iloprost. Furthermore, the MCT-induced increase in matrix metalloproteinase-2 and -9 activities and tenascin-C expression was suppressed.

CONCLUSIONS:

We conclude that the inhalation of iloprost reverses PAH and vascular structural remodeling in MCT-treated rats. This regimen suggests the possibility of an antiremodeling therapy in PAH.

• Authors: Ralph Theo Schermuly, Hüseyin Yilmaz, Hossein Ardeschir Ghofrani, Kathrin Woyda, Soni Pullamsetti, Andreas Schulz, Tobias Gessler, Rio Dumitrascu, Norbert Weissmann, Friedrich Grimminger, Werner Seeger
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 172 Issue 3 Pg. 358-63 (Aug 01 2005) ISSN: 1073-449X [Print] United States
• PMID: 15879421 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Vasodilator Agents
• Monocrotaline
• Iloprost

Topics

• Administration, Inhalation
• Animals
• Disease Models, Animal
• Hypertension, Pulmonary (chemically induced, drug therapy, physiopathology)
• Iloprost (administration & dosage, pharmacology)
• Monocrotaline (pharmacology)
• Pulmonary Artery (drug effects)
• Rats
• Rats, Wistar
• Vasodilator Agents (administration & dosage, pharmacology)
• Ventricular Pressure (drug effects)