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Departments of 2 Medicine and Cardiovascular Center and 1 Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
In contrast to its constrictor
effects on peripheral arteries, 20-hydroxyeicosatetraenoic acid
(20-HETE) is an endothelial-dependent dilator of pulmonary arteries
(PAs). The present study examined the hypothesis that the vasodilator
effects of 20-HETE in PAs are due to an elevation of intracellular
calcium concentration ([Ca2+]i) and the
release of nitric oxide (NO) from bovine PA endothelial cells (BPAECs).
BPAECs express cytochrome P-450 4A (CYP4A) protein and
produce 20-HETE. 20-HETE dilated PAs preconstricted with U-46619 or
norepinephrine and treated with the cytochrome P-450
inhibitor 17-octadecynoic acid and the cyclooxygenase inhibitor
indomethacin. The dilator effect of 20-HETE was blocked by the NO
synthase inhibitor N
-nitro-L-arginine methyl ester
(L-NAME) or by removal of endothelium. 20-HETE
significantly increased [Ca2+]i and NO
production in BPAECs. 20-HETE-induced NO release was blunted by removal
of extracellular calcium, as well as NO synthase inhibitors
(L-NAME). These results suggest that 20-HETE dilates PAs at
least in part by increasing [Ca2+]i and NO
release in BPAECs.
cytochrome P-450; calcium transients; pulmonary artery endothelial cells; vasodilation; 20-hydroxyeicosatetraenoic acid
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