Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol

Abstract

Endothelial dysfunction is more prevalent in African Americans (AA) compared to whites. We hypothesized that nebivolol, a selective β-1 antagonist that stimulates NO, will improve endothelial function in AA with hypertension when compared to metoprolol. In a double-blind, randomized, cross-over study, 19 AA hypertensive subjects were randomized to a 12-week treatment period with either nebivolol 10mg or metoprolol succinate 100mg daily. Forearm blood flow (FBF) was measured using plethysmography at rest and after intra-arterial infusion of acetylcholine, and sodium nitroprusside to estimate endothelium-dependent and independent vasodilation, respectively. Physiologic vasodilation was assessed during hand-grip exercise. Measurements were repeated after NO blockade with L-NG-monomethylarginine (L-NMMA), and after inhibition of endothelium-derived hyperpolarizing factor (EDHF) with tetraethylammonium chloride (TEA). NO blockade with L-NMMA produced a trend toward greater vasoconstriction during nebivolol compared to metoprolol treatment period (21% vs 12% reduction in FBF, p=0.06, respectively). This difference was more significant after combined administration of L-NMMA and TEA (p<0.001). Similarly, there was a contribution of NO to exercise-induced vasodilation during nebivolol but not during metoprolol treatment. There were significantly greater contributions of NO and EDHF to resting vasodilator tone and of NO to exercise-induced vasodilation with nebivolol compared to metoprolol in AA with hypertension.

Rethinking Endothelial Dysfunction as a Crucial Target in Fighting Heart Failure

“…Blood pressure medications have also been explored, yielding mixed results. Specifically, nebivolol, a β 1 -selective receptor blocker with NO-potentiating effects, demonstrated efficacy in improving endothelial function 89, 90. Conversely, metoprolol, a β 1 -selective receptor blocker, and spironolactone, an aldosterone antagonist, had minimal to no effects on endothelial function 91, 92…”

Effects of nebivolol versus other antihypertensive drugs on the endothelial dysfunction in patients with essential hypertension

“…Ten clinical trials and 689 patients were included in this analysis, of which 128 patients were randomized in one double-blind, parallel-group design trial, 90 randomized in three double-blind crossover design trials, 214 randomized in two single-blind, parallel-group design trials, 187 randomized in three-open design trials, and 70 randomized in one unreported design trial (Table 3). The patients received nebivolol, ranging from 5 mg [20] to 10 mg [13], or control antihypertensives including β-blockers (metoprolol [13,21], carvedilol [20,22], atenolol [14,[23][24][25], bisoprolol [26]) or other antihypertensives (olmesartan [11], nifedipine [24], amlodipine [24], telmisartan [24], perindopril [24]). One of these trials compared the effects of combined use of nebivolol and enalapril with the combination of atenolol and enalapril [14], and another showed an effect difference between nebivolol and atenolol on the background of 2.5 mg bendrofluazide [25].…”

“…The treatment time ranged from 2 [14] to 48 [24] weeks. In two trials [13,25], FBF measurement, other than FMD, was obtained using a venous occlusion strain gauge plethysmograph to evaluate the endothelial function. The characteristics of the included trials are shown in Table 3.…”

“…A meta-analysis with moderate methodological quality involving 5547 participants indicates that impaired brachial FMD is significantly relevant to the development of cardiovascular outcomes [12]. Forearm blood flow (FBF) is an invasive measurement to evaluate the endothelial dysfunction by venous occlusion plethysmography (VOP) [13]. Similarly, the dilatation of the peripheral arteries in FBF method was also induced by reactive hyperemia with a blood pressure cuff, and the change in the FBF values were recorded [14].…”

Nebivolol and Endothelial Dysfunction in Patients With Essential Hypertension: A Reputation Saver of β‐Blockers?

“…We have read with great interest the recently published article by Neuman and coworkers 1 in which they hypothesized that nebivolol, a selective b 1 -antagonist that stimulates nitric oxide (NO), improves endothelial function in African Americans with hypertension when compared with metoprolol. In that well-designed study, the authors found evidence for NO bioavailability at rest during treatment with both nebivolol and metoprolol succinate in hypertensive African American patients, with a clear trend for a greater contribution of NO during nebivolol therapy.…”