Clinical pharmacodynamics of nebivolol: new evidence of nitric oxide-mediated vasodilating activity and peculiar haemodynamic properties in hypertensive patients

Abstract

New evidence from recently completed clinical studies performed with nebivolol, a highly selective beta-1 beta-blocker, endowed with additional vasodilating activity mediated by nitric oxide (NO) endothelial release, confirm previous findings that nebivolol differs from other beta-blocking agents and that the combination of beta-1 blockade and NO-mediated vasodilation not only potentiates the blood pressure lowering activity, but leads to a broader favourable haemodynamic profile, which is clinically relevant to the treatment of hypertensive patients. In particular, six new studies focusing on the vasodilation properties of nebivolol demonstrated that: (i) its blood pressure lowering effect is accompanied by a vasodilating action that is seen after single and chronic administration of the usual antihypertensive oral dose of 5 mg once daily; (ii) the vasodilation can be documented systemically, at various regional vascular beds and skin microcirculation, and is accompanied by increased small arterial distensibility; (iii) the NO-endothelium-dependency of its vasodilating action is shown by the model of forearm or cutaneous vasodilating response to acetylcholine and by the blockade of the nebivolol-induced local vasodilation by a blocker of the arginine-NO cascade, L-NMMA. Two more studies demonstrated the ability of nebivolol to increase NO concentrations through preservation of NO from oxidative degradation, and not only by stimulation of its synthesis. Finally, two studies confirmed the favourable haemodynamic action of nebivolol on both systolic and diastolic function and, in particular, an increase in stroke volume, associated with reduction in vascular resistance, resulting in a maintained cardiac output despite reduced heart rate. These properties consistently differentiate nebivolol from non-vasodilating beta-blockers, such as those used for the active comparative studies, i.e. atenolol, metoprolol or bisoprolol. The observation that nebivolol enhances or restores NO-mediated vasodilation in hypertensive patients has important therapeutic implications in view of the well-established protective role of NO against cardiovascular risk factors, and particularly the development of atherosclerosis. Similarly, the favourable haemodynamic profile of nebivolol, as described by the new investigations (preservation of cardiac output, reduction of peripheral resistance and improved diastolic function) appear to have clinically relevant benefits on the impairment in systolic and/or diastolic function often complicating the hypertension.