Cytochrome P450 epoxygenase gene function in hypoxic pulmonary vasoconstriction and pulmonary vascular remodeling

Hypertension
Peter PokreiszStefan Janssens

Abstract

We assessed pulmonary cytochrome P450 (CYP) epoxygenase expression and activity during hypoxia and explored the effects of modulating epoxygenase activity on pulmonary hypertension. The acute hypoxic vasoconstrictor response was studied in Swiss Webster mice, who express CYP2C29 in their lungs. Animals were pretreated with vehicle, the epoxygenase inhibitor (N-methylsulfonyl-6-[2-propargyloxyphenyl] hexanamide) or an inhibitor of the soluble epoxide hydrolase. Whereas the epoxygenase inhibitor attenuated hypoxic pulmonary constriction (by 52%), the soluble epoxide hydrolase inhibitor enhanced the response (by 39%), indicating that CYP epoxygenase-derived epoxyeicosatrienoic acids elicit pulmonary vasoconstriction. Aerosol gene transfer of recombinant adenovirus containing the human CYP2C9 significantly elevated mean pulmonary artery pressure and total pulmonary resistance indices, both of which were sensitive to the inhibitor sulfaphenazole. The prolonged exposure of mice to hypoxia increased CYP2C29 expression, and transcript levels increased 5-fold after exposure to normobaric hypoxia (FIO2 0.07) for 2 hours. This was followed by a 2-fold increase in protein expression and by a significant increase in epoxyeicosatrienoic acid...Continue Reading

References

Jan 1, 1990·Kidney International·M L SchwartzmanN G Abraham
Nov 1, 1996·Journal of Virology·N MitterederB C Trapnell
Jan 1, 1997·Advances in Experimental Medicine and Biology·J Z TanG H Gurtner
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·T C HeB Vogelstein
Oct 16, 1999·Nature·B FisslthalerR Busse
Jan 25, 2000·American Journal of Physiology. Heart and Circulatory Physiology·H C ChampionA L Hyman
Feb 9, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·D ZhuE R Jacobs
Jun 14, 2000·American Journal of Respiratory and Critical Care Medicine·L KissF Grimminger
Aug 30, 2000·Prostaglandins & Other Lipid Mediators·J H Capdevila, J R Falck
Dec 21, 2000·American Journal of Physiology. Cell Physiology·P J Smith, J Trimarchi
Mar 10, 2001·Trends in Cardiovascular Medicine·I Fleming
Oct 27, 2001·Circulation Research·I Fleming
Jun 5, 2002·The Journal of Clinical Investigation·Fumito IchinoseWarren M Zapol
Mar 8, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Scott EarleyBenjimen R Walker
Nov 26, 2003·Progress in Lipid Research·Arthur A SpectorNeal L Weintraub
May 5, 2004·Respiratory Physiology & Neurobiology·Norbert WeissmannFriedrich Grimminger
Jun 8, 2004·Current Drug Metabolism·C Fradette, P Du Souich
Oct 16, 2004·The New England Journal of Medicine·Harrison W Farber, Joseph Loscalzo
Dec 1, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·U Ruth MichaelisIngrid Fleming
Dec 14, 2004·Journal of Applied Physiology·Rohit MoudgilStephen L Archer
Jan 11, 2005·Cardiovascular Research·Voahanginirina RandriamboavonjyIngrid Fleming
Jan 19, 2005·British Journal of Pharmacology·Paul M VanhoutteStefano Taddei
Feb 9, 2005·Circulation·Jason X-J Yuan, Lewis J Rubin

❮ Previous
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Citations

Mar 13, 2010·Pflügers Archiv : European journal of physiology·William B Campbell, Ingrid Fleming
Oct 20, 2011·Cancer Metastasis Reviews·Ingrid Fleming
Nov 3, 2007·Vascular Pharmacology·Shahrzad ElmiIsmail Laher
Oct 2, 2009·Nature Reviews. Drug Discovery·John D Imig, Bruce D Hammock
Aug 26, 2009·The Journal of Biological Chemistry·Eduardo Barbosa-SicardIngrid Fleming
Aug 30, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Benjamin KeserüIngrid Fleming
Aug 10, 2011·Current Opinion in Lipidology·Ingrid Fleming
Sep 26, 2008·The Journal of Pharmacology and Experimental Therapeutics·Kimberly L FifeDeanna L Kroetz
Dec 31, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Xiao-Ru YangJames S K Sham
Feb 5, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Dong SunAn Huang
Feb 3, 2012·Physiological Reviews·John D Imig
Feb 2, 2010·American Journal of Respiratory Cell and Molecular Biology·Changlong ZhengDao Wen Wang
Dec 20, 2011·American Journal of Respiratory Cell and Molecular Biology·Lei WangKent E Pinkerton
Oct 25, 2012·The Journal of Clinical Investigation·Liming WangWolfgang M Kuebler
May 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ding AiYi Zhu
Mar 8, 2011·Critical Care Medicine·Ali HoueijehLaurent Storme
May 31, 2011·Expert Opinion on Drug Metabolism & Toxicology·Patrick du Souich, Caroline Fradette
Apr 23, 2013·Drug Metabolism Reviews·Abdulaziz M S AlsaadAyman O S El-Kadi
Mar 12, 2013·Prostaglandins & Other Lipid Mediators·Ara AskariDavid Bishop-Bailey
Mar 25, 2015·Pflügers Archiv : European journal of physiology·Thibaud ParpaiteThomas Ducret
Jan 22, 2008·Trends in Cardiovascular Medicine·Ingrid Fleming
Feb 13, 2008·Archives of Biochemistry and Biophysics·Todd R HarrisBruce D Hammock
Dec 8, 2006·Trends in Pharmacological Sciences·Brandon T LarsenDavid D Gutterman
Sep 12, 2006·Cardiovascular Drug Reviews·John D Imig
Jun 20, 2012·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Dong SunAn Huang
May 4, 2010·Cardiovascular Therapeutics·Hong QiuNipavan Chiamvimonvat
Jan 29, 2011·Congestive Heart Failure·Ning LiNipavan Chiamvimonvat
Jul 6, 2013·Molecular Nutrition & Food Research·David BalgomaCraig E Wheelock
Aug 22, 2006·European Journal of Pharmacology·Laurentzio M PopescuSorin Simion
Dec 14, 2006·Prostaglandins & Other Lipid Mediators·Ingrid Fleming
Sep 30, 2015·Basic Research in Cardiology·Puneet Kaur Randhawa, Amteshwar Singh Jaggi

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