Calcium-activated potassium channels mask vascular dysfunction associated with oxidized LDL exposure in rabbit aorta.
Endothelium-dependent vasodilation is impaired in atherosclerosis. Oxidized low density lipoprotein (ox-LDL) plays an important role, possibly through alterations in G-protein activation. We examined the effect of acute exposure to ox-LDL on the dilator responses of isolated rabbit aorta segments. We sought also to evaluate the specificity of this dysfunction for dilator stimuli that traditionally operate through a Gi-protein mechanism. Aortic segments were prepared for measurement of isometric tension. After contraction with prostaglandin F2alpha, relaxation to thrombin, adenosine diphosphate (ADP), or the endothelium-independent agonists, sodium nitroprusside (SNP) or papaverine was examined. Maximal relaxation to thrombin was impaired in the presence of ox-LDL (17.7+/-3.7% p<0.05) compared to control (no LDL) (52.6+/-4.0%). Ox-LDL did not affect maximal relaxation to ADP or SNP. However, in the presence of charybdotoxin (CHTX: calcium-activated potassium channel inhibitor) ox-LDL impaired relaxation to ADP (17.4+/-3.2%). CHTX did not affect control (no LDL) responses to ADP (69.6+/-5.0%) or relaxation to thrombin or papaverine. In conclusion, ox-LDL impairs relaxation to thrombin, but in the case of ADP, calcium-activated potassium channels compensate to maintain this relaxation.
Bocker
J M
JM
Department of Internal Medicine, University of Iowa Hospitals, Iowa City, USA.
Miller
F J
FJ
Oltman
C L
CL
Chappell
D A
DA
Gutterman
D D
DD
D000818:Animals; D001012:Aorta, Abdominal / Q000502:physiology; D001161:Arteriosclerosis / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006937:Hypercholesterolemia / Q000503:physiopathology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects*
D008077:Lipoproteins, LDL; D015221:Potassium Channels; C099252:oxidized low density lipoprotein