Nebivolol reverses endothelial dysfunction in essential hypertension: a randomized, double-blind, crossover study.
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 beta-blocker, could improve endothelial dysfunction. We tested this hypothesis by comparing the effects of nebivolol and atenolol on endothelial function.


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.
Tzemos
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Hypertension Research Centre, Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and Medical School, Dundee, United Kingdom. n.tzemos@dundee.ac.uk
Lim
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PO
MacDonald
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TM
D000109:Acetylcholine / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001262:Atenolol / Q000627:therapeutic use; D001539:Bendroflumethiazide / Q000627:therapeutic use; D001578:Benzopyrans / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000068577:Nebivolol; D009599:Nitroprusside / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D001578:Benzopyrans; D004983:Ethanolamines; D014665:Vasodilator Agents; D000068577:Nebivolol; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D001262:Atenolol; D001539:Bendroflumethiazide; D000109:Acetylcholine