Digital plethysmography and arginine metabolism in prehypertension: effect of nebivolol therapy.

Prehypertension is an important phenotype for cardiovascular risk and development of established hypertension. To better understand the early circulatory changes in this group, the authors studied 34 patients with prehypertension (blood pressure 120-139/80-89 mm Hg) using digital plethysmography for measurement of blood flow and reactive hyperemic index (RHI). Arterial augmentation index (AI) was also measured. Because prehypertension is associated with endothelial dysfunction and decreased availability of nitric oxide (NO), indices of arginine metabolism (l-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, and l-citrulline) were measured. Nebivolol (5 mg/d), a vasodilating ß1 -antagonist with ß3 -agonist activity, was studied in a double-blind fashion for 8 weeks. Nebivolol increases the bioavailability of NO. Prehypertension was associated with normal RHI and baseline digital blood flow. AI was abnormal and associated with diastolic blood pressure. ADMA concentration was increased at baseline. After 8 weeks of nebivolol therapy, RHI, ADMA, symmetric dimethylarginine, and AI showed no significant change, but digital blood flow and l-citrulline levels were significantly increased. Prehypertension is associated with increased ADMA and evidence of increased arterial stiffness and preserved RHI. Nebivolol therapy is associated with digital vasodilation and increased NO production, as depicted by increased levels of l-citruline and mean digital blood flow.

The effect of nebivolol versus metoprolol succinate extended release on asymmetric dimethylarginine in hypertension.

This study sought to determine if metoprolol succinate ER (MET), and nebivolol (NEB), a ß1-AR with increased bioavailability of nitric oxide (NO), would have differing effects on plasma asymmetric dimethylarginine concentration in hypertensives. It was hypothesized that NEB, a ß1-AR antagonist and ß3-AR agonist with NO-releasing properties, and MET, only a ß1-AR antagonist, would have different effects on plasma asymmetric dimethylarginine (ADMA) concentration. Forty-one hypertensive subjects randomly received either 50 mg of MET (n = 19) or 5 mg of NEB (n = 22) for 4 weeks followed by 100 mg MET and 10 mg NEB for 4 weeks. ADMA and insulin-like growth factor-1 (IGF-1) were measured by enzyme-linked immunosorbent assay kit; endothelial progenitor cells were estimated using fluorescein-labeled monoclonal antibody to KDR and CD133 receptors; arterial augmentation index was measured by radial tonometry. Baseline systolic/diastolic blood pressure was 155.1 ± 18.7/85.3 ± 12.5 mm Hg for MET subjects and 157.6 ± 20.7/87.1 ± 14.0 mm Hg for NEB subjects. Baseline ADMA was 0.32 ± 0.123 µmol/L in the MET group and 0.4035 ± 0.1378 in the NEB group. ADMA increased 44.78% and 72% in the MET group at weeks 4 and 8 (P < .05 for both), respectively, without increase in the NEB group. At week 8, augmentation index was increased in the MET group (P < .05). IGF-1 and endothelial progenitor cells were unchanged by treatment. Plasma ADMA and augmentation index are increased in a dose-dependent fashion by MET but not with NEB.