Nebivolol: a novel beta-blocker with nitric oxide-induced vasodilatation

Abstract

Nebivolol is a novel beta 1 -blocker with a greater degree of selectivity for beta 1 -adrenergic receptors than other agents in this class and a nitric oxide (NO)-potentiating, vasodilatory effect that is unique among beta-blockers currently available to clinicians (nebivolol is approved in Europe and is currently under review in the US). A NO-potentiating agent such as nebivolol may have an important role in hypertensive populations with reduced endothelial function such as diabetics, African-Americans and those with vascular disease. Nebivolol is a racemic mixture with beta-blocker activity residing in the d-isomer; in contrast, l-nebivolol is far more potent in facilitating NO release. Nebivolol is unique among betablockers in that, at doses <10 mg, it does not inhibit the increase in heart rate normally seen with exercise. The efficacy of nebivolol has been tested successfully in clinical trials against other agents including other beta-blockers, angiotensin-converting enzyme-inhibitors and calcium channel antagonists in patients with hypertension, angina, and congestive heart failure. The tolerability of nebivolol has been shown to be superior to that of atenolol and metoprolol. In controlled clinical trials, nebivolol has a side effect profile that is similar to placebo, in particular as it relates to fatigue and sexual dysfunction. This article will review published clinical data regarding this cardioselective beta-blocker. Keywords: nebivolol, hypertension, beta-blocker IntroductionGoal blood pressure (BP), defined as <140/90 mm Hg in uncomplicated hypertension, is attained by only 34% of hypertensive patients in the US (Chobanian et al 2003), 24% of patients in France (Chamontin et al 1998), and 13% of patients in Canada (Joffres et al 2001). These low rates of achieving goal BP indicate that a more aggressive approach to BP management is required on a global scale. One of the most important classes of antihypertensive agents, beta-blockers play a critical role in reducing cardiovascular risk in hypertensive patients. A meta-analysis including almost 19 000 patients concluded that beta-blocker therapy was associated with a 42% reduction in heart failure, a 29% reduction in stroke risk, and a 7% reduction in coronary heart disease in hypertensive patients (Psaty et al 1997). The specific mechanism of action of beta-blockers that reduces BP is not completely understood, however, likely mechanisms include an effect on heart rate, inhibition of the sympathetic nervous system, and inhibition of the renin-angiotensin system. Nebivolol is a novel, highly selective beta-blocker with nonadrenergic vasodilating properties. It has been approved for the treatment of essential hypertension and congestive heart failure in Europe and is currently under review for the treatment of hypertension in the US. PharmacokineticsNebivolol is a racemic mixture of equal proportions of d-and l-isomers. The betablocker activity resides in the d-isomer while the facilitation of nitric oxide (NO)

Does Nebivolol Prevent Contrast‐Induced Nephropathy in Humans?

“…It has a vasodilatory effect via increasing NO availability. 28 Also, it has antioxidant properties that already have been proven. 29 Based on these characteristics of nebivolol, Toprak et al conducted an experimental study investigating the protective effect of nebivolol on CIN in rats.…”

Effect of Nebivolol on Endothelial Dysfunction in Coronary Artery Disease Patients -An Open Label Randomized Controlled Clinical Trial (NEDCAD)

“…This is in accordance with the data from earlier clinical trials on the improved quality of life and tolerance of patients to Nebivolol as compared to atenolol and metoprolol. 15,16 There were no differences in the angina episodes between the two groups. The results of the study show that one month of therapy with Nebivolol in coronary artery disease patients with hypertension causes significant reduction in MDA.…”

The effect of nebivolol on the production of nitric oxide induced by bacterial lipopolysaccharide and peptidoglycan in mice

“…Nebivolol is a novel third generation β1-adrenoceptor blocker [17][18][19][20] advocated for the treatment of hypertension. It is unique among all β1-adrenoceptor blockers in that it possesses a vasodilatory property attributed to synthesis of NO [21,22] as well as to increasing NO bioavailability by decreasing the oxidative stress [23][24][25][26][27].…”

“…It is unique among all β1-adrenoceptor blockers in that it possesses a vasodilatory property attributed to synthesis of NO [20,21] as well as to increasing NO bioavailability by decreasing the oxidative stress [22][23][24][25][26]. In addition, Ladage et al [27] reported that the endothelium-dependent increase in NO induced by nebivolol was due to stimulation of β 3 -adrenoceptors and estrogen receptors.…”