Nebivolol produces endothelium-dependent vasodilation by increasing nitric oxide release and decreasing oxidative stress, contributing to its efficacy and tolerability as an antihypertensive agent.
Nebivolol (Bystolic) is a cardioselective beta 1 (beta(1))-adrenergic receptor blocker with endothelium-dependent vasodilating properties. The endothelium-dependent relaxation induced by nebivolol is blocked by inhibitors of nitric oxide synthase (NOS) and guanylate cyclase. Nebivolol also increases in vitro and in vivo nitric oxide (NO), which is an essential signaling molecule involved in the maintenance of cardiovascular homeostasis. This review summarizes the data involving nebivolol and NO bioavailability. Endothelium-dependent relaxation of blood vessels, which is impaired in hypertensive animals and humans, is reversed by nebivolol treatment. Animals exhibiting endothelial dysfunction also show an improvement in NO-cyclic guanosine monophosphate (cGMP) signaling and an increase in NO bioavailability when treated with nebivolol. When blood vessel and cultured endothelial cells from hypertensive animals are treated with nebivolol, there is a decrease in superoxide production and an increase in the expression and activity of endothelial NOS (eNOS). As a result of the increased bioavailability of NO, nebivolol also increases in vivo arterial distensibility, glomerular filtration rate, and renal plasma flow. In normotensive volunteers, nebivolol infusion increases the forearm blood flow, an effect that is blocked by inhibitors of NOS and restored by the NOS substrate, L-arginine. In hypertensive patients, chronic treatment with nebivolol improves endothelium-dependent vasodilation induced by acetylcholine and shear stress and reverses endothelium-dependent vasoconstriction. Furthermore, nebivolol displays distinct hemodynamic properties in patients that include improvements in stroke volume and a decrease in peripheral vascular resistance. These studies demonstrate that nebivolol produces endothelium-dependent vasodilation by increasing NO release, decreasing oxidative stress to increase NO bioavailability, or both. The NO-dependent vasodilatory action of nebivolol, coupled with its high beta(1)-adrenergic receptor selectivity, is unique among the clinically available beta-blockers and contributes to its efficacy and improved tolerability (e.g., less fatigue and sexual dysfunction) as an antihypertensive agent.
Gupta et al. (Wed,) conducted a review in Hypertension. Nebivolol was evaluated. Nebivolol produces endothelium-dependent vasodilation by increasing nitric oxide release and decreasing oxidative stress, contributing to its efficacy and tolerability as an antihypertensive agent.