Abstract
20-Hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P-450 metabolite of arachidonic acid, is a vasoconstrictor in the systemic circulation and a vasodilator in the adult pulmonary circulation. Little is known about the vasoactive properties of 20-HETE in the newborn pulmonary circulation. The objectives of this study were to determine the vascular effects of 20-HETE and to explore the signaling mechanism(s) that mediate these effects in newborn pulmonary resistance-level arteries (PRA). Our findings demonstrate that, in contrast to the adult pulmonary circulation where 20-HETE mediates vasodilation, it causes constriction in newborn PRA at resting tone. Furthermore, inhibition of cyclooxygenase (COX) with indomethacin augments 20-HETE-induced constriction. The enhanced constrictor response to 20-HETE under conditions of COX inhibition is abolished in endothelium-disrupted PRA, suggesting that 20-HETE either stimulates endothelium-derived COX to release a counteracting vasodilator or is rapidly metabolized by COX to a less potent vasoconstrictor. 20-HETE-induced constriction is significantly inhibited by blocking calcium-dependent K + (KCa) channels and the thromboxane-PGH2 receptor. Altogether, our data indicate that the vascular actions of 20-HETE are partially mediated via the activation of KCa channels and are significantly modulated by interactions with the COX-prostaglandin pathway.
Original language | English (US) |
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Pages (from-to) | L360-L365 |
Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
Volume | 287 |
Issue number | 2 31-2 |
DOIs | |
State | Published - Aug 2004 |
Externally published | Yes |
Keywords
- Calcium-dependent channels
- Cyclooxygenase
- Cytochrome P-450
- Pulmonary resistance arteries
- Thromboxane-PGH receptor
ASJC Scopus subject areas
- Physiology
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology