Differences between Basal Lung Levels of Select Eicosanoids in Rat and Mouse

Abstract

Metabolites of arachidonic acid play an important role in mediating inflammation, cell proliferation, and oxidative stress that contribute to many pulmonary diseases. We hypothesized that the substantial differences between rats and mice in their responses to experimental pulmonary hypertensive stimuli would be associated with parallel differences in their basal eicosanoid profile. Rat and mouse lung extracts were subjected to liquid chromatography tandem mass spectrometry that was optimized for simultaneous separation and rapid quantification of the major hydroxyeicosatetraenoic acids (HETEs) and prostaglandins (PGs). Basal levels (pg/μg protein) of arachidonic acid metabolites differed significantly between rat and mouse lungs. Median values of the following major eicosanoids were significantly higher in mouse than in rat lungs: 5-HETE, 8-HETE, 12-HETE, 15-HETE, PGE2, and PGI2, as well as isoprostane-E2 and -F2α. In addition, the PGI2/TXB2 ratio was increased in mouse relative to rat lungs. On the basis of the important roles that these compounds play in determining pulmonary vascular tone, the differences in select eicosanoid profiles, especially the PGI2/TXB2 ratio, between rat and mouse lungs may underlie the interspecies differences in susceptibility to the development of pulmonary hypertension.

Isolation and characterisation of alveolar type II pneumocytes from adult bovine lung

“…Cells cultured in this way formed alveolar-like structures as reported previously 14 . The reason our cultures did not achieve ALI is unclear; we postulate that it may be due to interspecies differences, which have been previously shown to affect study outcomes 38 , 39 , or due to different culture conditions 33 .…”

Increased Eicosanoid Levels in the Sugen/Chronic Hypoxia Model of Severe Pulmonary Hypertension

“…1 ). In the context of our present rat model studies, it may be relevant that there are differences in the basal levels of lung tissue eicosanoids between rat and mouse [ 43 ].…”

Plasma 12‐ and 15‐Hydroxyeicosanoids are Predictors of Survival in Pulmonary Arterial Hypertension

“…Lipid extraction and analyses were carried out on homogenates of harvested lungs and RVs and analyzed by liquid chromatography–mass spectrometry (LC/MS/MS; appendix, available online). 28…”

“…Hemodynamic measurements were obtained at the end of the exposure period via a continuous pressure transducer catheter inserted through the right jugular vein and advanced to the right ventricle (RV). 14,28 After catheterization, the animals were euthanized, their thoraxes were opened, and their lungs and RVs were harvested immediately, weighed, and stored at −80°C. The protocol was approved by the Institutional Animal Care and Use Committee at Tufts Medical Center and was conducted in accordance with the National Institute of Health Guidelines for the Care and Use of Laboratory Animals.…”