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Inhibition of Soluble Epoxide Hydrolase Augments Hypoxic Pulmonary Vasoconstriction and Improves Gas Exchange in Mice
Author(s) -
Beloiartsev Arkadi,
Ventocilla Christian,
Winkler Jeffrey D.,
Bloch Kenneth D.,
Zapol Warren M.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1140.1
Subject(s) - hypoxic pulmonary vasoconstriction , epoxide hydrolase 2 , lung , pulmonary artery , anesthesia , hypoxia (environmental) , vasoconstriction , medicine , chemistry , perfusion , pulmonary hypertension , pharmacology , oxygen , biochemistry , organic chemistry , enzyme
Recent studies report that cytochrome P‐450‐derived epoxyeicosatrienoic acids (EETs) increase pulmonary vascular tone. We hypothesized that inhibiting the metabolism of EETs by inhibition of soluble epoxide hydrolase (sEH) would augment hypoxic pulmonary vasoconstriction (HPV) and improve gas exchange. Mice were anesthetized, intubated, and ventilated at F I O 2 =1. Animals received an i.v. infusion of the sEH inhibitor, IK‐950, or vehicle 30 minutes prior to assessing HPV. After thoracotomy, pulmonary artery pressure (PAP) and left lung blood flow (Q LPA ) were measured before and during transient inferior vena cava occlusion. Left lung pulmonary vascular resistance (PVR L ) was calculated from the slope of the PAP‐Q LPA relationship. The pulmonary vasoconstrictor response to unilateral left lung hypoxia was estimated by comparing PVR L before and after left main stem bronchial occlusion (LMBO). Infusion of vehicle or IK‐950 did not change baseline hemodynamic parameters. LMBO increased PVR L , without changing PAP in both vehicle‐and IK‐950‐pretreated mice. Increase in PVR L during LMBO was greater in mice pretreated with IK‐950 than in those pretreated with vehicle (Table). PaO 2 after LMBO was greater in mice pretreated with IK‐950 than in those pretreated with vehicle. Taken together, these results indicate that IK‐950 acts as a selective pulmonary vasoconstrictor of hypoxic lung regions, enhancing the perfusion of ventilated lung regions.