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(Circulation. 2001;104:511.)
© 2001 American Heart Association, Inc.

Brief Rapid Communications

Nebivolol Reverses Endothelial Dysfunction in Essential Hypertension

A Randomized, Double-Blind, Crossover Study

Nikolaos Tzemos, MRCP; Pitt O. Lim, MRCP; Thomas M. MacDonald, MD, FRCP, FESC

From the Hypertension Research Centre, Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee (N.T., T.M.M.), and the Department of Cardiology, Wales Heart Research Institute, University of Wales College of Medicine, Cardiff (P.O.L.), United Kingdom.

Correspondence to Dr Nikolaos Tzemos, Hypertension Research Centre, Department of Clinical Pharmacology and Therapeutics, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom, DD1 9SY. E-mail n.tzemos{at}dundee.ac.uk

Background— Vascular endothelial dysfunction may predict future atherosclerosis. Hence, an antihypertensive agent that reverses endothelial dysfunction and lowers blood pressure might improve the prognosis of patients with hypertension. We hypothesized that nebivolol, a vasodilating ß-blocker, could improve endothelial dysfunction. We tested this hypothesis by comparing the effects of nebivolol and atenolol on endothelial function.

Methods and Results— Twelve hypertensive patients with a mean ambulatory blood pressure of 154±7/97±10 mm Hg were randomized after a 2-week placebo run-in period (baseline) in a double-blind, crossover fashion to 8-week treatment periods with either 5 mg of nebivolol with 2.5 mg of bendrofluazide or 50 mg of atenolol with 2.5 mg of bendrofluazide. Forearm venous occlusion plethysmography and intra-arterial infusions of acetylcholine and N^G-monomethyl-L-arginine (L-NMMA) were used to assess stimulated and basal endothelium-dependent nitric oxide release, respectively. Sodium nitroprusside was used as an endothelium-independent control. Nebivolol/bendrofluazide and atenolol/bendrofluazide each lowered the clinic blood pressure to the same extent (132±7/82±6 and 132±9/83±8 mm Hg, respectively; P<0.001 from baseline). The vasodilatory response to acetylcholine was significantly increased with nebivolol/bendrofluazide (maximum percentage change in forearm blood flow [mean±SEM], 435±27%, P<0.001) but not with atenolol/bendrofluazide. Similarly, the endothelium-dependent vasoconstrictive response to L-NMMA was significantly improved only with nebivolol treatment (percentage change in forearm blood flow, -54±5%; P<0.001). The response to sodium nitroprusside was not different between treatments, suggesting that the endothelium-independent pathway was unaffected.

Conclusions— Nebivolol/bendrofluazide increased both stimulated and basal endothelial nitric oxide release, whereas for the same degree of blood pressure control, atenolol/bendrofluazide had no effect on nitric oxide bioactivity. Thus, nebivolol may offer additional vascular protection in treating hypertension.

Key Words: hypertension • endothelium • nitric oxide

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