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

Nebivolol, a chemically novel beta 1-adrenoceptor antagonist, acutely lowers blood pressure in spontaneously hypertensive rats, anaesthetised normotensive dogs, and hypertensive patients. We have investigated the actions of dl-nebivolol in five conscious normotensive rabbits (sham, mean blood pressure (BP) of 82.2 +/- 4.1 mm Hg, mean +/- SEM) and four hypertensive rabbits (renal wrap hypertension) (wrap, mean BP of 117.6 +/- 1.5 mm Hg). Nebivolol (1 mg/kg i.v.) did not significantly lower the BP or heart rate in either group 30 min after injection. In the same rabbits, on another day, after autonomic blockade (mecamylamine), nebivolol (0.1, 0.3, and 1.0 mg/kg i.v.) right shifted the bolus i.v. isoproterenol tachycardia dose-response curves by dose ratios of 5, 18, and 90 in sham rabbits, respectively, and 5, 11, and 23 in wrap rabbits, respectively, indicating significant cardiac beta 1-adrenoceptor antagonism. In guinea pig isolated right atria pretreated with atropine (1 microM) and desipramine (DMI, 0.1 microM), norepinephrine concentration-response curves were antagonised competitively by nebivolol (3-100 nM), giving a pKb of 7.90. In separate atria without DMI pretreatment, neither nebivolol (100 nM) nor propranolol (100 nM) had any significant effect on the increase in the rate of norepinephrine efflux following electrical field stimulation (0.5-2 Hz, 3 min). These findings suggest that at concentrations of nebivolol that show substantial beta 1-adrenoceptor antagonism, there is no evidence of hypotension or bradycardia nor additional effects on cardiac norepinephrine release. Why nebivolol lowers blood pressure in some species but not in the conscious rabbit is not known.
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PMID:Relationship between the sympatholytic action of nebivolol and hypotension. 138 20

This placebo-controlled multifactorial design trial assessed the antihypertensive efficacy of nebivolol, a novel cardioselective beta 1-blocker with vasodilating properties, and hydrochlorothiazide monotherapy and in combination. After a 4-week placebo period, 240 white patients with a mean daytime ambulatory blood pressure of > or = 90 mm Hg were randomized to receive either placebo, nebivolol (1, 5, or 10 mg), hydrochlorothiazide (12.5 or 25 mg), or one of the six possible combinations of nebivolol and hydrochlorothiazide for 12 weeks. A dose-related reduction in clinic and ambulatory blood pressure was demonstrated for each drug as monotherapy and for the two drugs in combination. Nebivolol, 5- and 10-mg doses, showed a larger effect than hydrochlorothiazide doses on clinic blood pressure and over the 24-h interval. Moreover, the combination doses had substantial antihypertensive effects that were sustained over the entire 24-h profile with a greater effect observed with the higher dose combinations. The reduction in ambulatory blood pressure was further substantiated by the reduction of blood pressure loads (% of BP > 140/90 mm Hg awake and > 120/80 mm Hg asleep) to as low as 11.5% with 10 mg of nebivolol combined with 25 mg of hydrochlorothiazide. Nebivolol and hydrochlorothiazide were well tolerated. We provided evidence that nebivolol, given as monotherapy or in combination with low dose of hydrochlorothiazide, is effective in reducing clinic and 24-h ambulatory blood pressure in patients with ambulatory hypertension. The results provided further evidence for the use of ambulatory blood pressure monitoring and factorial designs when investigating new antihypertensive agents.
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PMID:Treatment of ambulatory hypertensives with nebivolol or hydrochlorothiazide alone and in combination. A randomized, double-blind, placebo-controlled, factorial-design trial. 817 48

The aim of this double-blind, parallel group study was to compare the effects of nebivolol and atenolol on blood pressure (BP) and insulin sensitivity in hypertensive patients with type II, non-insulin dependent diabetes mellitus (NIDDM). After a 4-week run-in period on placebo, 30 patients (14 males and 16 females) aged 43 to 69 years, with stable NIDDM and mild to moderate hypertension (DBP > or =95 and <116 mm Hg) were randomised to receive either nebivolol 5 mg or atenolol 50 mg, both administered once daily for 6 months. At the end of the placebo and the active treatment periods, supine and standing BP was measured, 24-h urinary C-peptide, HbA1c, plasma glucose and lipid levels were evaluated and an euglycaemic hyperinsulinaemic clamp was performed to evaluate insulin sensitivity: glucose infusion rate during the last 60 min of clamp and total glucose requirements were evaluated. Nebivolol 5 mg once daily was of an equivalent efficacy as atenolol 50 mg once daily at reducing supine and standing systolic and diastolic BP values. Neither beta-blocker adversely affected carbohydrate metabolism in terms of insulin sensitivity, whole body glucose utilization, HbA1c and 24-h urinary C-peptide excretion. No significant changes in cholesterol (total, high density and low density lipoprotein) and triglycerides plasma levels were observed with both beta-blockers. These findings indicate that, in hypertensive patients with NIDDM, ie, in subjects who have established insulin resistance, treatment with nebivolol and atenolol neither further deteriorated insulin sensitivity nor adversely affected the lipid profile.
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PMID:Comparative effects of nebivolol and atenolol on blood pressure and insulin sensitivity in hypertensive subjects with type II diabetes. 941 86

A double-blind, randomised, parallel-group trial was conducted in patients with essential hypertension in British general practices, of nebivolol 5 mg, atenolol 50 mg, and placebo each given once daily. Both active drugs, in comparison with placebo, caused highly significant and similar reductions in systolic and diastolic pressures without orthostatic effect, and small significant falls in heart rate. Both active drugs were well tolerated, nebivolol marginally more so. Nebivolol, a long-acting, cardioselective, vasodilating beta-blocker which acts partly via the l-arginine/nitric oxide mechanism, appears potentially valuable for the treatment of hypertension.
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PMID:Nebivolol vs atenolol and placebo in essential hypertension: a double-blind randomised trial. 950 55

Nebivolol is a new cardioselective beta-blocking agent possessing vasodilatory properties involving the endothelium. This compound is a dl-racemic mixture. The d-enantiomer is responsible for the beta-blocking properties whereas the l-enantiomer induces a vasodilation via a nitric oxide (NO) mechanism. Nebivolol is an unique agent that appears promising for the management of patients with hypertension, coronary heart disease or congestive heart failure.
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PMID:[Nebivolol: a beta blocker with vasodilator properties]. 1080 47

An enhanced vasoconstriction and vascular smooth muscle cell proliferation are involved in pathogenesis of hypertension. Beta3-blockers are effective for treatment of hypertensive patients. Recently the new beta1-receptor blocker nebivolol showed a different hemodynamic profile from those of other classic beta-blockers. In this study we hypothesized that nebivolol may also have different effects on smooth muscle cell proliferation compared with other beta-blockers such as atenolol. Human aortic smooth muscle cells (SMCs) were cultured, and cell growth was determined by increase in cell number. Growth-signaling molecules such as mitogen-activated protein kinase (p42mapk) and S6-kinase (p70S6K) and cell-cycle regulatory proteins (i.e., Cdk2, p27Kip1, and pRb) were analyzed by immunoblotting. In cultured human aortic SMCs, cell number was markedly increased in response to 5% fetal calf serum (FCS) over 6 days (87 +/- 11 x 10(3)/well), which was inhibited by nebivolol (10(-8)-10(-5) M; 25 +/- 2 x 10(3)/well; n = 6; p < 0.05), but not by atenolol. 5% FCS activated p42mapk, S6K, and Cdk2, but downregulated p27Kip1 and hyperphosphorylated pRb. Nebivolol prevented Cdk2 activation without influencing p42mapk, S6K, pRB, and p27Kip1. Thus, the new beta1-blocker nebivolol exhibits antiproliferative effect on human SMC through inactivation of Cdk2. This effect of nebivolol may have advantages over other beta-blockers in treatment of patients with cardiovascular disease.
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PMID:Nebivolol inhibits human aortic smooth muscle cell growth: effects on cell cycle regulatory proteins. 1083 16

Effects were studied of nebivolol, metoprolol and enalapril maleat on the state of endothelium-dependent vasodilatation of arterioles in patients with essential arterial hypertension. Nebivolol has been shown to effectively decrease blood pressure and restore endothelium-dependent vasodilatation to a grater degree, than enalapril or metoprolol.
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PMID:[Effects of nebivolol, metoprolol and enalapril maleate on the state of endothelium-dependent arteriolar vasodilation in patients with essential hypertension]. 1151 14

Nebivolol, a racemic mixture of (S,R,R,R) and (R,S,S,S) enantiomers, is the most beta1-selective adrenoceptor antagonist currently available for clinical use. However, its haemodynamic effects differ from those of classical beta-adrenoceptor antagonists as a result of a vasodilating action. Nebivolol is devoid of alpha-adrenergic antagonist actions, and the detailed mechanism of its vasodilator action is unknown. Nebivolol relaxes precontracted strips of canine coronary and carotid artery only if the endothelium is intact, and such relaxation is antagonized by inhibition of nitric oxide (NO) synthase, implicating the endothelial L-arginine/NO mechanism. Nebivolol and atenolol have been compared in phenylephrine preconstricted dorsal hand veins of 11 healthy men. Nebivolol caused venodilation, which was antagonized by N(G)-monomethyl-L-arginine (LNMMA), whereas atenolol did not, suggesting that such a mechanism could also operate in human veins. Venodilation could be functionally important in reducing cardiac pre-load. Beta2-adrenoceptor stimulation increases forearm blood flow (FBF) by activating the L-arginine/NO pathway but nebivolol lacks direct beta2-adrenoceptor agonist activity. Resistance vessel function has been studied by measuring FBF by venous occlusion plethysmography in healthy men during brachial artery infusions of racemic nebivolol and its enantiomers, atenolol, carbachol (a stable analogue of acetylcholine that vasodilates this vascular bed, in part by activating the L-arginine/NO pathway), nitroprusside (a NO donor that causes non-endothelium-dependent vasodilation through the same effector mechanism as endothelium-dependent agonists) and LNMMA. Nebivolol (354 microg/min) increased FBF by 91 +/- 18% (mean +/- SE, n = 8; p < 0.01), whereas an equimolar dose of atenolol had no significant effect. LNMMA inhibited responses to nebivolol and carbachol to a significantly greater extent than it reduced responses to nitroprusside. Antagonism of nebivolol by LNMMA was abolished by L-arginine. The (S,R,R,R) and (R,S,S,S) enantiomers caused similar increases of FBF. To determine whether brachial artery infusion of nebivolol causes vasodilation in the forearm resistance vasculature of patients with essential hypertension and to investigate the possible involvement of the L-arginine/NO pathway, we studied otherwise healthy volunteers with uncomplicated essential hypertension. Nebivolol (88.5, 177 and 354 microg/min, each dose for 6 min) caused similar vasodilatation as in normotensive subjects, and these responses were sensitive to inhibition by LNMMA. If acute effects of nebivolol on the L-arginine/NO pathway persist during chronic treatment of patients with hypertension or heart failure, this could reduce cardiac after-load as well as pre-load, improve organ perfusion and reduce atherogenesis and thrombosis.
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PMID:Nebivolol: endothelium-mediated vasodilating effect. 1181 87

Nebivolol, compared with classical beta-blockers, exerts a high selectivity for beta-adrenergic receptors and also reduces peripheral vascular resistance by modulating nitric oxide (NO) release. This dual mechanism of action leads to effective control of blood pressure at a low degree of beta-blockade and explains the lack of any interference with lipid metabolism. For the same reason, the tolerability profile of nebivolol is highly favorable compared with the classical beta-blockers, with less fatigue and dyspnea in hypertensive subjects, and with an improvement of functional capacity and exercise tolerance in patients with left ventricular dysfunction. Furthermore, contrary to atenolol and propranolol, nebivolol does not diminish specific airway conductance. Compared with other first-line antihypertensive agents, nebivolol was shown to be better tolerated than nifedipine and enalapril, and to have a positive effect on general wellbeing. Among the currently available antihypertensive drugs, nebivolol therefore appears to have a most alteractive safety and tolerability profile, which can be attributed to its NO-mediated effects allowing effective control of hypertension at a lower degree of beta-blockade than with first-generation beta-blockers.
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PMID:Metabolic effects and safety profile of nebivolol. 1181 91

Nebivolol is a lipophilic beta 1-blocker. It is devoid of intrinsic sympathomimetic or membrane stabilising activity but appears to have nitric oxide-mediated vasodilatory effects. Nebivolol 5 mg once daily is well tolerated in patients with hypertension. Adverse events are infrequent, transient and mild to moderate. Those reported most often include headache, fatigue, paraesthesias and dizziness. Several studies reported no signs of orthostatic hypotension with Nebivolol.
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PMID:[Nebivolol treatment in essential arterial hypertension]. 1209 33


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