The impact of third-generation Beta-blocker antihypertensive treatment on endothelial function and the prothrombotic stateEffects of smoking

Vyssoulis, Gregory P.; Marinakis, A.G.; Aznaouridis, Konstantinos; Karpanou, Eva A.; Arapogianni, Athina N.; Cokkinos, Dennis V.; Stefanadis, Christodoulos

doi:10.1016/j.amjhyper.2004.03.668

Cited by 38 publications

(20 citation statements)

References 26 publications

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“…Similar to the results obtained with metoprolol, administration of up to 100 mg per day of atenolol over six months did not change levels of tPA-Ag and PAI-1-Ag or PAI-1 activity (26). In another study (1), 550 consecutive patients with uncomplicated hypertension were treated with celiprolol, carvedilol or nebivolol monotherapy. Plasma levels of fibrinogen and homocysteine, and serum levels of PAI-1 decreased in the celiprololand nebivolol-treated groups.…”

Section: Discussionsupporting

confidence: 59%

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

Tarighi

Kürüm

Demir

et al. 2007

Canadian Journal of Cardiology

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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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Section: Discussionsupporting

confidence: 59%

“…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).…”

mentioning

confidence: 99%

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

Tarighi

Kürüm

Demir

et al. 2007

Canadian Journal of Cardiology

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“…An existing study has shown that the effects of nebivolol on endothelial function and the prothrombotic state were more pronounced in hypertensive smokers than in hypertensive nonsmokers (as measured by decreases in fibrinogen, plasminogen activator inhibitor-I, and homocysteine [Vyssoulis et al 2004]). The failure of the beta-blockers, celiprolol and carvedilol, to elicit such pronounced effects in the same study demonstrates that the finding was unique to nebivolol and was not a class effect.…”

Section: Discussionmentioning

confidence: 99%

Effects of the vasodilating beta-blocker nebivolol on smoking-induced endothelial dysfunction in young healthy volunteers

Schmidt

Flick²,

Jahn³

et al. 2008

VHRM

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Objective:To assess the effect of nebivolol, a highly selective third generation β 1 -adrenoceptor antagonist with an endothelium-dependent vasodilatory action, on smoking-induced endothelial dysfunction. Research design and methods:This open-label study examined the effect of 14 daily doses of 5 mg nebivolol on forearm blood fl ow in 21 healthy, young, male, light smokers (Յ5 cigarettes/day), measured by plethysmography on Days 1, 7, and 14. The primary endpoint was the difference in forearm blood fl ow after smoking one standard cigarette from baseline (Day 1) until treatment end on Day 14. Secondary outcomes included the difference in forearm blood fl ow between Day 1 and Day 7 compared with Day 14 before and after smoking, the effect of nebivolol on blood coagulation parameters, high-sensitive-C-reactive protein (hs-CRP), and the safety and tolerability of nebivolol. Results: Nebivolol for 14 days did not signifi cantly affect forearm blood fl ow after smoking. On Day 7 of nebivolol treatment, forearm blood fl ow after smoking was signifi cantly greater than blood fl ow before smoking (increase of 0.44 mL/min; p = 0.00656). Serum level of hs-CRP showed a marked decrease from Day 1 to Day 14. No changes in coagulation parameters were observed over the course of nebivolol treatment. Nebivolol was well tolerated throughout the study. Conclusions:The increase in forearm blood fl ow and the marked decrease in hs-CRP over 14 days of treatment suggest that nebivolol has a positive effect on endothelial function in light smokers, but larger studies are required to confi rm these observations.

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“…As demonstrated in animal models of coronary artery occlusion and reperfusion, localized endothelial swelling and protrusions, are predominantly confined to the capillary bed [12], indicating that endothelial dysfunction plays an important role in tissuelevel perfusion. Notably, carvedilol is an alpha1 and nonselective beta-adrenergic receptor antagonist with antioxidative properties known to protect against endothelial dysfunction [13][14][15]; we hypothesized that it may be also effective in preventing from myocardial no-reflow. Furthermore, myocardial no-reflow was always associated with microvascular structural disintegrity (structural no-reflow), which caused vascular leakiness.…”

Section: Introductionmentioning

confidence: 99%

Carvedilol preserves endothelial junctions and reduces myocardial no-reflow after acute myocardial infarction and reperfusion

Zhao

Yang

Shang

et al. 2007

International Journal of Cardiology

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The impact of third-generation Beta-blocker antihypertensive treatment on endothelial function and the prothrombotic stateEffects of smoking

Cited by 38 publications

References 26 publications

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

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

Effects of the vasodilating beta-blocker nebivolol on smoking-induced endothelial dysfunction in young healthy volunteers

Carvedilol preserves endothelial junctions and reduces myocardial no-reflow after acute myocardial infarction and reperfusion

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