Human pulmonary arteries dilate to 20-HETE, an endogenous eicosanoid of lung tissue

The American Journal of Physiology
E K BirksE R Jacobs

Abstract

We investigated the effect of 20-hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid metabolite of the cytochrome P-450 (cP450) 4A pathway, on human pulmonary arterial tone. 20-HETE elicited a dose-dependent and indomethacin-inhibitable vasodilation of isolated small pulmonary arteries. Whole lung microsomes metabolized [24C]arachidonic acid into 20-HETE and a variety of leukotrienes, epoxyeicosatrienoic acids, and prostanoids. Indomethacin blocked formation of prostanoids without effects on the conversion of arachidonate into 20-HETE, 20-HETE was converted by lung microsomes into prostanoids, raising the possibility that 20-HETE may be metabolized by cyclooxygenase enzymes in vascular tissue to a vasodilatory compound. Western blots probed with a polyclonal antibody to cP450 4A identified a protein of approximately 50 kDa immunologically similar to the cP450 4A in rat liver. We conclude that small arteries from human lungs dilate upon exposure to 20-HETE in a cyclooxygenase-dependent manner and that the proteins and enzymatic activity required to synthesize this product are present in lungs. Our observations suggest that cP450 enzyme products could be endogenous modulators of pulmonary vascular tone.

Citations

Sep 29, 2000·American Journal of Physiology. Heart and Circulatory Physiology·D ZhuE R Jacobs
Jan 22, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Caroline MorinEric Rousseau
Feb 3, 2012·Physiological Reviews·J T SylvesterJeremy P T Ward
Mar 1, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Alan H StephensonAndrew J Lonigro
Apr 12, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Thomas A ParkerSteven H Abman
Jul 31, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Caroline MorinEric Rousseau
Mar 17, 2005·The Journal of Pharmacology and Experimental Therapeutics·Adebayo O Oyekan
Aug 30, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Benjamin KeserüIngrid Fleming
Jun 20, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Xiang FangArthur A Spector
Feb 21, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Igor V KizubSachin A Gupte
Apr 13, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mamta FuloriaJudy L Aschner
Oct 22, 2002·American Journal of Physiology. Renal Physiology·Jun-Ichi KaideMichal Laniado-Schwartzman
Feb 9, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·D ZhuE R Jacobs
Jun 19, 2002·Journal of Applied Physiology·Daling ZhuElizabeth R Jacobs
Dec 21, 2000·American Journal of Physiology. Heart and Circulatory Physiology·E R Jacobs, D C Zeldin
Jul 29, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Asma YaghiDavid G McCormack
Apr 12, 2005·Annual Review of Pharmacology and Toxicology·Deanna L Kroetz, Fengyun Xu
Sep 18, 2002·Journal of Applied Physiology·Ming YuElizabeth R Jacobs

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