title: Nebivolol: haemodynamic effects and clinical significance of combined beta-blockade and nitric oxide release.
abstract: Nebivolol is a third-generation beta-adrenergic receptor antagonist (beta-blocker) with high selectivity for beta(1)-adrenergic receptors. In addition, it causes vasodilatation via interaction with the endothelial L-arginine/nitric oxide (NO) pathway. This dual mechanism of action underlies many of the haemodynamic properties of nebivolol, which include reductions in heart rate and blood pressure (BP), and improvements in systolic and diastolic function. With respect to BP lowering, the NO-mediated effects cause a reduction in peripheral vascular resistance and an increase in stroke volume with preservation of cardiac output. Flow-mediated dilatation and coronary flow reserve are also increased during nebivolol administration. Other haemodynamic effects include beneficial effects on pulmonary artery pressure, pulmonary wedge pressure, exercise capacity and left ventricular ejection fraction. In addition, nebivolol does not appear to have adverse effects on lipid metabolism and insulin sensitivity like traditional beta-blockers. The documented beneficial haemodynamic effects of nebivolol are translated into improved clinical outcomes in patients with hypertension or heart failure. In patients with hypertension, the incidence of bradycardia with nebivolol is often lower than that with other currently available beta-blockers. This, along with peripheral vasodilatation and NO-induced benefits such as antioxidant activity and reversal of endothelial dysfunction, should facilitate better protection from cardiovascular events. In addition, nebivolol has shown an improved tolerability profile, particularly with respect to events commonly associated with beta-blockers, such as fatigue and sexual dysfunction. Data from SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure) showed that significantly fewer nebivolol versus placebo recipients experienced the primary endpoint of all-cause mortality or cardiovascular hospitalization. The benefits of nebivolol therapy were shown to be cost effective. Thus, nebivolol is an effective and well tolerated agent with benefits over and above those of traditional beta-blockade because of its effects on NO release, which give it unique haemodynamic effects, cardioprotective activity and a good tolerability profile.
authors.affiliation: Department of Cardiology, Institute for Cardiovascular Research VU, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Otto
authors.initials: O
authors.lastname: Kamp
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.forename: Silvia
authors.initials: S
authors.lastname: Bugatti
authors.forename: Luca
authors.initials: L
authors.lastname: Bettari
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dei Cas
authors.forename: Natalia
authors.initials: N
authors.lastname: Petrini
authors.forename: Livio
authors.initials: L
authors.lastname: Dei Cas
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001120:Arginine / Q000627:therapeutic use; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D017079:Exercise Tolerance / Q000187:drug effects; D006333:Heart Failure / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D000068577:Nebivolol; D009569:Nitric Oxide / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013318:Stroke Volume / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001578:Benzopyrans; D002121:Calcium Channel Blockers; D004983:Ethanolamines; D014665:Vasodilator Agents; D000068577:Nebivolol; D009569:Nitric Oxide; D001120:Arginine