13-HODE increases intracellular calcium in vascular smooth muscle cells.
13-Hydroxyoctadecadienoic acid (HODE) (2 microM) consistently increased porcine aortic and pulmonary artery smooth muscle cell calcium concentrations ([Ca2+]i), whereas 9-HODE and linoleic acid had no significant effect in the aortic cells and a much lesser effect in the pulmonary artery cells. A transient increase in [Ca2+]i occurred with as little as 50 nM 13-HODE. Structural specificity for elevation of [Ca2+]i also was seen with the monohydroxyeicosatetraenoic acids (HETEs), with 12-HETE but not 5- or 15-HETE increasing [Ca2+]i. 13-HODE, but not 9-HODE, increased smooth muscle cell guanosine 3',5'-cyclic monophosphate (cGMP) levels. The [Ca2+]i increase produced by 13-HODE was dependent on extracellular calcium and was inhibited by the calcium channel blockers verapamil and nifedipine and by KT-5823, a cGMP-dependent kinase inhibitor. A similar increase in [Ca2+]i was produced by 8-bromo-cGMP. These results suggest that 13-HODE, a 15-lipoxygenase product formed from linoleic acid, can act as a lipid mediator in vascular smooth muscle. It raises smooth muscle cGMP, causing a secondary increase in [Ca2+]i due to Ca2+ influx through a cGMP kinase-dependent L-type channel.
Stoll
L L
LL
Department of Anesthesia, University of Iowa, Iowa City 52242.
Morland
M R
MR
Spector
A A
AA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism*; D008041:Linoleic Acids / Q000494:pharmacology*; D044243:Linoleic Acids, Conjugated; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D013552:Swine
D006893:Hydroxyeicosatetraenoic Acids; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; C024347:9-hydroxy-10,12-octadecadienoic acid; C024348:13-hydroxy-9,11-octadecadienoic acid; D006152:Cyclic GMP; D002118:Calcium