Inhaled iloprost reverses vascular remodeling in chronic experimental pulmonary hypertension.
BACKGROUND
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.


OBJECTIVE
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.
Schermuly
Ralph Theo
RT
Department of Internal Medicine, Justus Liebig Universität Giessen, Germany. ralph.schermuly@innere.med.uni-giessen.de
Yilmaz
Hüseyin
H
Ghofrani
Hossein Ardeschir
HA
Woyda
Kathrin
K
Pullamsetti
Soni
S
Schulz
Andreas
A
Gessler
Tobias
T
Dumitrascu
Rio
R
Weissmann
Norbert
N
Grimminger
Friedrich
F
Seeger
Werner
W
D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D016285:Iloprost / Q000008:administration & dosage / Q000494:pharmacology*; D016686:Monocrotaline / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017725:Ventricular Pressure / Q000187:drug effects
D014665:Vasodilator Agents; D016686:Monocrotaline; D016285:Iloprost