Format

Send to

Choose Destination
PLoS One. 2015 Mar 18;10(3):e0120157. doi: 10.1371/journal.pone.0120157. eCollection 2015.

Increased eicosanoid levels in the Sugen/chronic hypoxia model of severe pulmonary hypertension.

Author information

1
Pulmonary and Critical care Medicine Division, Victoria Johnson Center for Lung Research, Richmond, Virginia, United States of America; Department of Internal Medicine, Montefiore Mount Vernon Hospital, Westchester, New York, United States of America.
2
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University-School of Medicine, Richmond, Virginia, United States of America.
3
Pulmonary and Critical care Medicine Division, Victoria Johnson Center for Lung Research, Richmond, Virginia, United States of America.
4
Division of Cardiology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
5
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University-School of Medicine, Richmond, Virginia, United States of America; Hunter Holmes McGuire Veterans Administration Medical Center, Richmond, Virginia, United States of America; The Massey Cancer Center, Richmond, Virginia, United States of America; Virginia Commonwealth University Reanimation Engineering Science Center (VCURES), Richmond, Virginia, United States of America.

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.

PMID:
25785937
PMCID:
PMC4364907
DOI:
10.1371/journal.pone.0120157
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center