Impaired vascular function in small resistance arteries of LOX-1 overexpressing mice on high-fat diet.
OBJECTIVE
LOX-1 is a major vascular receptor for oxidized low-density lipoprotein (oxLDL). In this study, we analysed the impact of LOX-1 overexpression and high dietary fat intake on vascular function in small resistance arteries.


RESULTS
Relaxation of mesenteric arteries was measured using a wire myograph. Compared with the control group, mice overexpressing LOX-1 on a high-fat diet (FD) had preserved vascular smooth muscle relaxation, but impaired endothelium-dependent relaxation via NO. Vascular NO availability was decreased by exaggerated formation of reactive oxygen species and decreased endothelial NO synthase expression. Endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation via cytochrome P450 metabolites was increased in LOX-1 + FD animals, but did not completely compensate for the loss of NO. Currents of calcium-activated potassium channels with large conductance (BKCa channels) were measured by the voltage-clamp method. The BKCa current amplitudes were not altered in endothelial cells, but highly increased in vascular smooth muscle cells from resistance arteries of LOX-1-overexpressing mice on FD. BK(Ca) currents were activated by low-dose H2O2 and cytochrome P450 metabolites 11,12-EET and 14,15-EET as EDHF in control mice.


CONCLUSIONS
LOX-1 overexpression and FD caused functional changes in endothelial and vascular smooth muscle cells of small resistance arteries.
Eichhorn
Birgit
B
Department of Pharmacology and Toxicology, Medical Faculty Carl Gustav Carus, University of Technology, Fetscherstr. 74, D-01307 Dresden, Germany. birgit.eichhorn@tu-dresden.de
Muller
Gregor
G
Leuner
Anja
A
Sawamura
Tatsuya
T
Ravens
Ursula
U
Morawietz
Henning
H
D000818:Animals; D001835:Body Weight; D002417:Cattle; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000009:adverse effects*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D014655:Vascular Resistance
D004041:Dietary Fats; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008055:Lipids; C495138:Olr1 protein, mouse; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; D052250:Nitric Oxide Synthase Type III