We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Increased Eicosanoid Levels in the Sugen/Chronic Hypoxia Model of Severe Pulmonary Hypertension.
- Authors
Al-Husseini, Aysar; Wijesinghe, Dayanjan S.; Farkas, Laszlo; Kraskauskas, Donatas; Drake, Jennifer I.; Van Tassel, Ben; Abbate, Antonio; Chalfant, Charles E.; Voelkel, Norbert F.
- Abstract
Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx) rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not prevent the development of pulmonary angioobliteration. In contrast, DEC blunted the muscularization of pulmonary arterioles and reduced the number of fully obliterated lung vessels. DEC treatment of SuHx rats, after the lung vascular disease had been established, reduced the degree of PAH, the number of obliterated arterioles and the degree of perivascular inflammation. We conclude that the non-specific anti-inflammatory drug DEC affects developing PAH and is partially effective once angioobliterative PAH has been established.
- Subjects
EICOSANOIDS; HYPOXEMIA; PULMONARY hypertension; INFLAMMATION; LIPOXYGENASES; CYCLOOXYGENASES; METABOLITES
- Publication
PLoS ONE, 2015, Vol 10, Issue 3, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0120157