[The experimental study on changes of endothelial nitric oxide synthase and plasminogen activator inhibitor-1 protein in the canine atrial fibrillation model].
OBJECTIVE
To evaluate the changes in the expressions of endothelial nitric oxide synthase (eNOS) and plasminogen activator inhibitor-1 (PAI-1) and the alterations of nitric oxide (NO) concentration in atrial endocardium in atrial fibrillation (AF) in order to investigate the mechanisms that contribute to thrombosis.


METHODS
In canine AF was produced with rapid atrial pacing at 400 bpm for 6 weeks, whereas the controls had no atrial pacing. NO production was measured by NO-specific microelectrode. The expression of endocardial eNOS and PAI-1 protein were determined by Western blot analysis and immunohistochemical Staining. Plasma levels of PAI-1 were analysed by Enzyme-linked immunoadsorbent assay.


RESULTS
Left atrial NO concentration was decreased in AF than that in controls [(23.4 +/- 5.8)nmol/L vs (63.8 +/- 16.1)nmol/L, P < 0.01]. Endocardial eNOS expression was also significantly decreased (855 +/- 217 vs 2320 +/- 694, P < 0.05), whereas the expression of the PAI-1 was increased (3164 +/- 827 vs 1371 +/- 352, P < 0.01). Neither NO concentration, nor PAI-1, eNOS expression were altered in the right atria at the same time. A significant increase for plasma levels of PAI-1 was also detected in AF group. No correlation was found between eNOS and PAI-1 protein expression (r = 0.217, P > 0.05).


CONCLUSIONS
In the canine model AF was associated with a marked decrease in endocardial NOS expression and NO concentration and with an increase in PAI-1 expression in the left atrium, which may contribute to the thrombosis in AF.
Han
Wei
W
Department of Cardiology, The First Clinical College, Harbin Medical University, Harbin 150001, China.
Li
Wei-min
WM
Song
Li-yun
LY
Li
Yue
Y
Yang
Shu-sen
SS
Huang
Yong-lin
YL
Gan
Run-tao
RT
Kou
Jun-jie
JJ
Geng
Jian-qiang
JQ
D000818:Animals; D001281:Atrial Fibrillation / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D013927:Thrombosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
D017395:Plasminogen Activator Inhibitor 1; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III