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

PloS One
Aysar Al-HusseiniNorbert F Voelkel

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.

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Citations

Apr 21, 2016·Expert Review of Cardiovascular Therapy·Norbert F VoelkelMark R Nicolls
Jun 3, 2016·Pulmonary Circulation·Nadine Al-NaamaniIoana R Preston
Sep 30, 2016·Pulmonary Circulation·Salil SharmaMansoureh Eghbali
Jan 10, 2020·Journal of the American Heart Association·Soban UmarMansoureh Eghbali
Jun 26, 2017·Respiratory Research·Jie YinXiaolu Li
Oct 16, 2019·Frontiers in Pharmacology·Mythili DileepanSavita P Rao
Dec 26, 2018·Antioxidants & Redox Signaling·Victor TsengC Michael Hart
Apr 8, 2020·Pulmonary Circulation·Norbert F Voelkel, Marc Peters-Golden
Jun 7, 2019·Antioxidants & Redox Signaling·Olga RafikovaRuslan Rafikov
Aug 28, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Ethan D KwanDaniela Valdez-Jasso

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Methods Mentioned

BETA
Assay
Protein Assay
confocal microscopy

Software Mentioned

GraphPad
Elastica
AxioVision
ImageJ
GraphPad Prism

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