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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nebivolol is known as a highly selective beta1-adrenoceptor antagonist. Based on the reported vasodilator effect of nebivolol, we examined the cellular mechanisms by which the drug induces renal artery vasodilation, an issue of potential relevance for condition associated with high blood pressure. To this purpose, myograph and patch-clamp techniques were used. Small mouse renal arteries were placed in the myograph chamber, and after the optimal concentration for the vasodilator effect of nebivolol was established (50 microM), the arteries were further investigated to assess the potential contribution of nitric oxide (NO) and of Ca2+ ions to the nebivolol-induced effect, by exposing the arteries to the specific inhibitors such as N(G)-nitro-L-arginine methylester (L-NAME, 100 microM), ethylenglycol-bis-(beta-amino-ethylen ester) N,N'-tetraacetic acid (EGTA, 4 microM) and thapsigargin (1 microM). The expression of NO synthase was evaluated by the Western-blot technique. Using myograph and patch-clamp techniques applied on intact renal artery, we investigated the role of beta2-adrenoceptors, of myoendothelial junctions and of Ca(2+)-activated K+ channels in the vasodilatory effects of nebivolol, using 100 microM butoxamine, 40 microM 18 beta-glycyrrhetinic acid, 1 mM tetraethylammonium, and 100 nM iberiotoxin, respectively. The results showed that the cellular mechanisms of the vasodilator effect of nebivolol on the renal artery entail (i) activation of the endothelial beta2-adrenoceptor, (ii) participation of [Ca2+]i, (iii) increase in NO and eNOS, and (iv) activation of Ca(2+)-activated K+ channels. The cellular mechanisms underlying vasodilator effect of nebivolol on the artery explain the favorable effect of this drug in hypertension.
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PMID:The cellular mechanisms involved in the vasodilator effect of nebivolol on the renal artery. 1568 Feb 67

Hypertensive patients with left ventricular hypertrophy (LVH) have increased QT dispersion, which is considered an early indicator of end-organ damage and a non-invasive marker of risk for clinically important ventricular arrhythmias and cardiac mortality. The purpose of this study was to examine the effect of nebivolol antihypertensive therapy on QT dispersion in hypertensive subjects. Twenty-five subjects (15 men and 10 women, mean age 53.6 +/- 4.5 years) with essential arterial hypertension and mild-to-moderate LVH (blood pressure: 147.2 +/- 6.2/90.6 +/- 3.8 mmHg; left ventricular mass indexed: 149.1 +/- 10.7 g/m(2)) were compared with 25 age-matched healthy control subjects. All the participants underwent a complete clinical examination, including electrocardiogram for QT interval measurements. The QT dispersion was defined as the difference between the longest and the shortest QT interval occurring in the 12-lead electrocardiogram. The QT dispersion was corrected (QTc) with Bazett's formula. Hypertensive subjects were treated with 5 mg daily of nebivolol. The ECG and echocardiogram were repeated after four weeks of treatment. At baseline, hypertensive patients showed QT dispersion (56.9 +/- 6.4 vs. 31.7 +/- 8.4 ms, P < 0.001) and QTc dispersion (58.3 +/- 6.2 vs. 33.2 +/- 7.8 ms, P < 0.001) significantly higher than control subjects. Four-week nebivolol treatment reduced blood pressure from 147.2 +/- 6.2/90.6 +/- 3.6 mmHg to 136.3 +/- 3.1/83.3 +/- 2.5 mmHg (P < 0.0001), and resting heart rate from 75.3 +/- 4.7 to 64.2 +/- 3.0 bpm (P < 0.001), without significant change in left ventricular mass (LVMi: 149.1 +/- 10.7 vs. 151.4 +/- 9.8 g/m(2), ns). Nebivolol-based treatment improved QT dispersion (56.9 +/- 6.4 vs. 40.5 +/- 5.8 ms, P < 0.001) and QTc dispersion (58.3 +/- 6.2 vs. 42.2 +/- 5.6 ms, P < 0.001), which remained higher than in control subjects (P < 0.001 in both cases). The reduction of QT dispersion did not correlate with arterial BP reduction. In conclusion, nebivolol reduced increased QT dispersion in hypertensive subjects after four weeks. This effect, occurred without any change in LVM, did not seem to be related to the blood pressure lowering and could contribute to reduce arrhythmias as well as sudden cardiac death in at-risk hypertensive patients.
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PMID:Effect of nebivolol on QT dispersion in hypertensive patients with left ventricular hypertrophy. 1574 Sep 30

Hypertension is a major risk factor for cardiovascular diseases; drugs that reduce blood pressure and simultaneously improve or reverse endothelian dysfunction, as nebivolol, may be advantageous in terms of cardiovascular protection. The objective of this study is to show the anti-hypertensive efficacy and safety of nebivolol (5 mg once a day) given to patients with arterial hypertension for 3 months. It should also provide information about drug's influence on laboratory tests--fasting blood glucose and serum cholesterol, triglyceride and creatinine concentrations. Six centers--Tuzla, Sarajevo, Mostar, Bihac, Zenica and Banja Luka participated in this prospective study with follow-up period of 3 months that included 3 visits. The study group consisted of 328 hypertensic patients. Results showed a significant decrease in both systolic and diastolic blood pressure and heart rate at the end of the study. Fasting blood glucose level and serum cholesterol, triglyceride and creatinine changed significantly during the study, with lower levels of all the tests. Nebivolol seems to be free from some of the problems that generally accompany not only the classical beta- blockers but sometimes also newer classes of antihypertensive drugs. With its high anti-hypertensive efficiency and safety, and presence of statically significant difference in laboratory tests and beneficial effects, absence of adverse interaction with glucose and lipid metabolism, patients treated with Nebivolol may show an optimal adherence to therapy.
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PMID:Effects of nebivolol on artery hypertension--multicentre study Bosnia and Herzegovina. 1577 2

The research was undertaken with the purpose to assess the efficiency of nebivolol for correction of thrombocyte aggregation capability in patients having arterial hypertension (AH) with metabolic syndrome (MS). 21 patients were administered nebivolol in a dose of 5 mg per day for a month. The dynamic changes in the following parameters were evaluated: anthropometric measurements, blood lipid spectrum, lipid peroxidation in serum and thrombocytes, antioxidative protectability of the liquid part of blood and platelets, thrombocyte aggregation activity. The results were processed using Student criterion and system multifactoral analysis. Nebivolol reduced peroxidation syndrome and optimized thrombocyte aggregation in patients with AH and MS. When administered for a long period of time, nebivolol is able to stabilize the achieved effect. Combining nebivolol application with use of non-drug means is necessary to reduce body weight in patients having AH with MS.
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PMID:[The influence of nebivolol on thrombocyte aggregation in patients with arterial hypertension with metabolic sydrome]. 1588 38

The beta-adrenergic receptor blockers play an important role in the management of cardiovascular disease, including hypertension and chronic heart failure. However, concerns regarding safety and tolerability with currently available agents can limit their use. The beta-blockers vary with regard to several pharmacologic properties, including beta1/beta2 selectivity, intrinsic sympathomimetic activity, and, with the newest beta-blockers, vasodilation. These pharmacologic differences may result in clinically important differences in tolerability and hemodynamic properties. Nebivolol is a novel beta-blocker with both a greater degree of selectivity for beta1-adrenergic receptors than other agents in this class and an ability to stimulate endothelial nitric oxide production, leading to vasodilation and other potential clinical effects. Published randomized, controlled, multicenter studies with nebivolol have shown that once-daily treatment significantly reduces systolic and diastolic blood pressure in patients with mild-to-moderate hypertension, compared with placebo, in a dose-dependent manner, and is well tolerated, with an adverse event profile similar to that of placebo. When compared with other beta-blockers as well as with other antihypertensive classes of agents in head-to-head trials, nebivolol demonstrated similar antihypertensive efficacy and a lower incidence of adverse events. Nebivolol has also been shown to significantly reduce morbidity and mortality in a large population of elderly patients with chronic heart failure, independent of left ventricular ejection fraction. Nebivolol is currently available in Europe for the management of hypertension and is expected to be available soon in the United States.
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PMID:The role of the new beta-blockers in treating cardiovascular disease. 1637 95

Although the regulation of arterial blood flow has been a subject of intensive medical research, the precise circulatory mechanisms involved are still not fully understood. It has been increasingly recognized that the endothelium plays a vital role in regulating vascular tone, structure, and function. A seminal discovery was made with the identification of endothelium-derived relaxing factor, a key mediator of vasodilation, which was later identified as nitric oxide (NO). Nitric oxide is synthesized from the amino acid L-arginine in the endothelium. Decreased bioavailability of NO is associated with arterial stiffness, hypertension, atherosclerosis, and cardiovascular disease (CVD). Nebivolol is a novel beta-blocker that is highly selective for beta1-adrenergic receptors. Nebivolol also causes vasodilation through a mechanism involving endothelium-derived NO. In clinical studies in hypertensive subjects, nebivolol significantly improves vasodilator responses to endothelium-dependent agonists such as acetylcholine. In addition, nebivolol significantly reduces pulse wave velocity (PWV), a measure of arterial stiffness, whereas the beta-blocker atenolol has no effect on PWV. Because endothelial dysfunction and arterial stiffness play an integral part in the early atherosclerotic process and are associated with poor outcomes and increased mortality, independent of blood pressure, the ability of nebivolol to enhance release of endothelium-derived NO may have significant clinical implications for the use of this agent in the treatment of hypertension and CVD.
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PMID:Exploring vascular benefits of endothelium-derived nitric oxide. 1637 96

Nebivolol, a selective beta-adrenoceptor (beta1-AR) antagonist, induces vasodilatation by an endothelium- and NO-cGMP-dependent pathway. However, the mechanisms involved in the vascular effect of nebivolol have not been established. Thus, we evaluated the role of alpha1 and beta3-ARs in nebivolol-induced vasodilatation. The responses to nebivolol were investigated in vitro in thoracic aortic rings isolated from male Sprague-Dawley rats. Nebivolol (0.1-10 microM) significantly shifted the concentration-response curve to phenylephrine, an alpha1-AR agonist, to the right in a concentration-dependent manner (pA2 = 6.5). Conversely, the concentration-response curve to endothelin 1 (ET1) was unaffected by nebivolol. In ET1-precontracted rings, nebivolol induced a concentration-dependent relaxation, which was unaffected by nadolol (a beta1/beta2-AR antagonist) but was significantly reduced by L-748,337 (a beta3-AR antagonist), endothelium removal or pretreatment with L-NMMA (an NOS inhibitor). Similar results were obtained with a beta3-AR agonist, SR 58611A. It was concluded that, in rat aorta, nebivolol-induced relaxation results from both inhibition of alpha1-ARs and activation of beta3-ARs. In addition, we confirmed that the endothelium and the NO pathway are involved in the vascular effect of nebivolol. The identification of these vascular targets of nebivolol indicate that it has therapeutic potential for the treatment of pathological conditions associated with an elevation of sympathetic tone, such as heart failure and hypertension.
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PMID:Mixed beta3-adrenoceptor agonist and alpha1-adrenoceptor antagonist properties of nebivolol in rat thoracic aorta. 1647 20

The study was aimed to assess influence of nebivolol (nebilet) on endothelial factors (NO and endothelin1) during treatment of salt-sensitive hypertensive patients. A total of 40 patients (18 females and 22 males, mean age 53,1+/-1,58 yrs) with mild (I stage) arterial hypertension (with diastolic pressure 90-99 mm Hg and/or systolic pressure 140-159 mm Hg) were studied. Twelve age matched healthy subjects (4 women and 8 males) composed control group. Salt sensitivity was detected by M. Weir (1993) method. Patients were divided in two groups: salt sensitive hypertension (group I, 16 patients) and salt-resistant hypertension (group II, 24 patients). Nebivolol (Nebilet, Berlin-Chemie, Germany) was administered to 25 patients in dosage of 5 mg once a day during two weeks. Our studies have showed that ET-1 plasma levels were significantly elevated in patients with essential hypertension, while NO was markedly reduced compared to control group. NO levels were slightly lower in salt-sensitive hypertensives than in salt-resistant patients (p>0,05). ET-1 levels expressed opposite changes: in patients with salt-sensitive hypertension ET-1 levels almost twice exceeded those of salt-resistant patients (p<0,01). After treatment with nebivolol NO plasma level in salt-sensitive hypertensives significantly increased in Group I and did not change significantly in salt-resistant patients. Only slight decrease in ET-1 levels was detected in both groups after taking nebilet. Nebilet (nebivolol) treatment has an influence only on NO levels and appears to be the most effective in salt-sensitive hypertension.
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PMID:Influence of nebivolol on endothelial dysfunction in salt-sensitive hypertension. 1670 29

Nebivolol has been adequately tested in clinical efficacy trials of patients with mild hypertension. Clinical efficacy trials or their meta-analyses did not accurately predict the outcome of subsequent large studies. The primary objective was to assess the efficacy/safety of nebivolol 5-10 mg daily in a nationwide study of patients with mild hypertension. Secondary objectives were (1) to compare efficacy/safety as monotherapy versus add-on therapy and (2) to assess the effect of nebivolol on ISH. This was an open-label, 6-week follow-up study of 6,356 patients with mild hypertension or ISH, as defined by the 1999 World Health Organization guidelines, recruited from 2,700 facilities. Previous monotherapies were continued except for beta-blockers. Results are reported as means+/-SDs. Intention-to-treat analysis is given. A total of 5,740 patients completed the study; of the withdrawals, 90% were lost for follow-up or were noncompliant, 38% were untreated before, 23% had beta-blockers. In the accumulated data, mean systolic and diastolic blood pressures fell by 24+/-14 and 13+/-9 mm Hg (both P<0.001). The differences between the blood pressure-reducing effects of nebivolol monotherapy and add-on therapy were not statistically significant: 28+/-16 and 22+/-14 mm Hg for systolic and 15+/-11 and 11+/-8 mm Hg for diastolic blood pressures. Adverse events were limited to 0.5% of the patients, no serious adverse events were observed. In the ISH patients, diastolic blood pressure fell by 4+/-6 mm Hg compared with 15+/-10 mm Hg in the no-ISH patients (P<0.01). Efficacy-safety effects of nebivolol in patients with mild hypertension can be generalized in a nationwide assessment. The efficacy of nebivolol as monotherapy and as the efficacy as add-on therapy are very similar. Nebivolol is highly efficacious in patients with ISH.
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PMID:Nationwide efficacy-safety study of nebivolol in mildly hypertensive patients. 1677 59

Nebivolol is a third-generation beta-adrenoceptor antagonist. It differs from other beta-adrenoceptor antagonists as it combines highly selective beta(1)-adrenoceptor antagonist properties with nitric oxide-mediated vasodilatory actions and beneficial effects on endothelial function. Nebivolol is approved in Europe and several other countries for the treatment of essential hypertension and in Europe for the treatment of stable mild or moderate chronic heart failure (CHF) in addition to standard therapies in elderly patients aged >or=70 years. Nebivolol is an effective antihypertensive agent and is well tolerated in patients with hypertension. The drug also effectively decreased the composite endpoint of mortality and cardiovascular hospital admission in elderly patients with CHF and was generally well tolerated in this population. Nebivolol should be considered as an alternative first-line treatment option for patients with uncomplicated mild to moderate essential hypertension and in elderly patients with CHF.
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PMID:Nebivolol: a review of its use in the management of hypertension and chronic heart failure. 1690 72


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