Effect of lysophosphatidylcholine on vasomotor functions of porcine coronary arteries.
BACKGROUND
Lysophosphatidylcholine (LPC) is a product of phosphatidylcholine hydrolysis by phospholipase A(2) and a mediator of the lipid-induced atherosclerotic changes. In this study, we determined the effects of LPC on vasomotor functions, oxidative stress, and endothelial nitric oxide synthase (eNOS) expression in porcine coronary arteries.


METHODS
Porcine coronary arteries were cut into 5-mm rings and were treated with LPC or antioxidant selenomethionine (SeMet). For the vasomotor studies, we used a myograph tension system. Levels of superoxide anion (O(2)(-)) were detected by the lucigenin-enhanced chemiluminescence method. The eNOS protein level was studied by immunohistochemistry with avidin-biotin complex immunoperoxidase procedure.


RESULTS
Endothelium-dependent relaxation in response to bradykinin was reduced by 36% and 81% for the rings treated with 12.5 and 25 mum of LPC, respectively, as compared with controls (P < 0.05). Endothelium-independent relaxation in response to sodium nitroprusside also was reduced by 63% after treatment with 25 mum LPC (P < 0.05). The O(2)(-) level was increased in the porcine arteries treated with 25 mum of LPC by 41% as compared with controls (P < 0.05). The antioxidant SeMet reversed the effects of LPC on vascular relaxation and O(2)(-) production. Immunoreactivity of eNOS in LPC-treated vessel rings also was reduced substantially.


CONCLUSIONS
LPC impairs endothelium-dependent and endothelium-independent vasorelaxation. This effect is associated with increased superoxide radical production and decreased eNOS activity and is practically reversed with the use of the antioxidant SeMet.
Safaya
Rakesh
R
Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.
Chai
Hong
H
Kougias
Panagiotis
P
Lin
Peter
P
Lumsden
Alan
A
Yao
Qizhi
Q
Chen
Changyi
C
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003331:Coronary Vessels / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress; D012645:Selenomethionine / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013552:Swine; D014664:Vasodilation / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects*
D000975:Antioxidants; D008244:Lysophosphatidylcholines; D013481:Superoxides; D012645:Selenomethionine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III