Nitric oxide contributes to 20-HETE-induced relaxation of pulmonary arteries.
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 ([Ca(2+)](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(omega)-nitro-L-arginine methyl ester (L-NAME) or by removal of endothelium. 20-HETE significantly increased [Ca(2+)](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 [Ca(2+)](i) and NO release in BPAECs.
Yu
Ming
M
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
McAndrew
Ryan P
RP
Al-Saghir
Rula
R
Maier
Kristopher G
KG
Medhora
Meetha
M
Roman
Richard J
RJ
Jacobs
Elizabeth R
ER
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D009994:Osmolar Concentration; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
D006893:Hydroxyeicosatetraenoic Acids; D014665:Vasodilator Agents; D009569:Nitric Oxide; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A; D002118:Calcium