Estrogen blocks homocysteine-induced endothelial dysfunction in porcine coronary arteries(1,2).
BACKGROUND
The objective of this study was to examine the effect of estrogen combined with homocysteine on vasomotor function and endothelial integrity in intact porcine coronary arteries.


METHODS
Pig coronary artery rings were incubated with estrogen, homocysteine, or estrogen and homocysteine for 24 h. Myographic analysis was performed with thromboxane A2 analog U46619 for contraction and bradykinin or sodium nitroprusside for relaxation. Endothelial nitric oxide synthase (eNOS) levels were determined by immunohistochemistry. Levels of superoxide anion were assessed by lucigenin-enhanced chemiluminescence analysis.


RESULTS
Endothelium-dependent vasorelaxation (bradykinin) for the homocysteine alone group was 62% compared with control (P < 0.05), and endothelium-dependent vasorelaxation for the estrogen alone group was 85% compared with control (P > 0.05). Endothelium-dependent vasorelaxation for the estrogen-homocysteine combined group was 79% compared with 89% for control (P > 0.05). There were no differences in endothelium-independent vasorelaxation (sodium nitroprusside) or in smooth muscle contractility (U46619) between all three groups and control. In addition, the eNOS immunoreactivity was declined in the homocysteine group and had no major change in the estrogen or estrogen plus homocysteine-treated group as compared with controls. The superoxide free radical measurement showed a marked increase in the homocysteine group, no major change from controls in the estrogen group, and a much-lessened effect in the combination of estrogen and homocysteine.


CONCLUSIONS
These data demonstrate that combining estrogen with homocysteine significantly blocks the effect of homocysteine on impairing endothelium-dependent vasorelaxation as well as on decreasing eNOS expression and increasing oxidative stress in porcine coronary arteries. This study suggests that estrogen may play a role in preventing homocysteine-mediated endothelial dysfunction and may be of benefit in the hyperhomocysteinemic patient.
Spencer
Todd A
TA
Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine and the Methodist Hospital, Houston, Texas 77030, USA.
Chai
Hong
H
Fu
Weiping
W
Ramaswami
Ganesh
G
Cox
Mitchell W
MW
Conklin
Brian S
BS
Lin
Peter H
PH
Lumsden
Alan B
AB
Yao
Qizhi
Q
Chen
Changyi
C
D000818:Animals; D001158:Arteries; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology*; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D004958:Estradiol / Q000494:pharmacology*; D006710:Homocysteine / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D013194:Staining and Labeling; D013481:Superoxides / Q000378:metabolism; D013552:Swine; D014664:Vasodilation / Q000187:drug effects
D004338:Drug Combinations; D006710:Homocysteine; D013481:Superoxides; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III