[Effect of Cilazapril on endothelial cell function and fibrinolysis system in the canine atrial fibrillation models].
OBJECTIVE
To investigate the effect of cilazapril on endothelial cell function and fibrinolysis system in the canine atrial fibrillation (AF) models.


METHODS
All canines were divided into three groups: (1) Control group, without atrial pacing; (2) Atrial pacing group, in which atrial fibrillation was established by rapid atrial pacing at 400 bpm for 6 weeks; (3) Atrial pacing together with cilazapril group, in which cilazapril was given before and after atrial pacing. Nitric oxide (NO) of atrial endocardium was measured with NO-specific microelectrode. The expression of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (tPA) protein in atrium was determined by Western Blot analysis and immunohistochemical staining. Plasma levels of von Willebrand Factor (vWF), PAI-1 and tPA were analyzed by enzyme-linked immunoadsorbent assay.


RESULTS
NO production from atrial endocardium was significantly increased in atrial pacing together with cilazapril group than atrial pacing group [(42.6 +/- 9.9) nmol/L vs (23.4 +/- 5.8) nmol/L, P < 0.05], whereas the plasma levels of vWF were decreased [(75.4 +/- 12.8)% vs (125.9 +/- 20.6)%, P < 0.05]. Compared to controls, the expression of atrium tPA protein in atrial pacing together with cilazapril group was significantly upregulated (4052 +/- 857 vs 1936 +/- 421, P < 0.05) and PAI-1 protein was downregulated (2487 +/- 542 vs 3164 +/- 827, P < 0.05). Cilazapril also significantly increased tPA antigen and decreased PAI-1 antigen in plasma.


CONCLUSIONS
Cilazapril can favorably improve endothelial function and resume the balance of fibrinolysis system in AF, which might be of beneficial to hypercoagulated state in AF.
Li
Wei-min
WM
Department of Cardiology, First Clinical College of Harbin Medical University, Harbin 150001, China.
Han
Wei
W
Liang
Zi-jun
ZJ
Wu
Dong-lai
DL
Huang
Yong-lin
YL
Cui
Shang-jin
SJ
Li
Yue
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D017315:Cilazapril / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D010959:Tissue Plasminogen Activator / Q000032:analysis
D000806:Angiotensin-Converting Enzyme Inhibitors; D017395:Plasminogen Activator Inhibitor 1; D017315:Cilazapril; D010959:Tissue Plasminogen Activator