The effects of nebivolol on fibrinolytic parameters in mild and moderate hypertensive patients

Abstract

T he vascular endothelium is a metabolically active paracrine organ. It regulates thrombogenicity, vascular tone, leukocyte adhesion, and platelet and smooth muscle function (1). While normal endothelium is in a nonthrombotic state, deterioration of the vascular endothelium results in the synthesis and release of procoagulant and anticoagulant substances from the disrupted vascular endothelium (2,3).One of the major risk factors for atherosclerosis is hypertension. Most of the studies on hypertensive subjects have shown that hypertension is associated with cardiovascular abnormalities marked by oxidative stress induction, endothelial dysfunction and derangement of the normal hemostatic and fibrinolytic balance (4-6). Optimal blood pressure (BP) control in hypertensive patients does not always lead to restoration of normal endothelial function, and drugs with comparable BPlowering effects do not counteract hypertension-induced endothelial dysfunction to a similar degree (7).Nebivolol is a selective beta 1 -adrenergic receptor antagonist that relaxes vascular smooth muscle by nitric oxide-and cyclic GMP-dependent mechanisms (8). Nebivolol reverses endothelial dysfunction in essential hypertension (9). The direct effect of nebivolol on endothelial function as assessed by the measurement of plasminogen activator inhibitor type 1 antigen (PAI-1-Ag), PAI-1 activity, tissue plasminogen activator antigen (tPA-Ag), tPA-Ag/PAI-1-Ag index, fibrinogen and euglobulin lysis time (ELT) has not been reported. The BACKGROUND: The aim of the present study was to investigate the effects of nebivolol (5 mg daily) on plasma levels of hemostatic and fibrinolytic endothelial function markers in mild or moderate hypertensive patients. METHODS AND RESULTS: Thirty-five (22 female, 13 male; mean ± SD 54.7±11.3 years of age) mild and moderate hypertensive patients were included the study. The mean systolic blood pressure [BP] was 160 mmHg (range 150 mmHg to 165 mmHg) and the mean diastolic BP was 100 mmHg (range 90 mmHg to 100 mmHg). Plasma tissue plasminogen activator antigen (tPA-Ag), plasminogen activator inhibitor type 1 antigen (PAI-1-Ag), PAI-1 activity, tPA-Ag/PAI-1-Ag index, fibrinogen and euglobulin lysis time were determined before and after two months of therapy. tPA-Ag and PAI-Ag levels were measured by ELISA. After this period, treatment with nebivolol (5 mg/day) in all patients was associated with a significant decrease in systolic BP and diastolic BP (P<0.001 for each), heart rate (P<0.01), fibrinogen (P<0.005) and euglobulin lysis time (P<0.01). The tPA-Ag and tPA-Ag/PAI-1-Ag index levels were increased significantly (P<0.001 for each) in all patients, but the PAI-1-Ag (P>0.05) and PAI-1 activity (P>0.05) did not show significant change. In the present study, there was no correlation between decreases in arterial BP and decreases in fibrinolytic parameters (P>0.05), but there was a positive, statistically significant correlation between fibrinogen and body mass index (P<0.001). CONCLUSIONS: The results indicated that, comp...

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Differential Effects of Nebivolol and Metoprolol on Insulin Sensitivity and Plasminogen Activator Inhibitor in the Metabolic Syndrome

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Pharmacological modulation of fibrinolytic response – In vivo and in vitro studies

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