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.
Conclusion: 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.