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

• Authors: Robert B. Neuman, Emory University; Salim Hayek, Emory University; Joseph C. Poole, Emory University; Ayaz Rahman, Emory University; Vivek Menon, Emory University; Nino Kavtaradze, Emory University; David Polhemus, Louisiana State University; Emir Veledar, Emory University; David J. Lefer, Louisiana State University; Arshed Quyyumi, Emory University
• Journal Title: Journal of Clinical Hypertension
• Volume: Volume 18, Number 3
• Publisher: Wiley: 12 months | 2016-03-01, Pages 223-231
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1111/jch.12649
• Subjects: Health Sciences, Public Health; Biology, Physiology; Biology, Molecular
• Keywords: Science & Technology; Life Sciences & Biomedicine; Peripheral Vascular Disease; Cardiovascular System & Cardiology; ENDOTHELIUM-DEPENDENT VASODILATION; EXERCISE-INDUCED VASODILATION; FOREARM RESISTANCE VESSELS; HYPERPOLARIZING FACTOR; VASCULAR RELAXATION; PEROXYNITRITE RELEASE; MENTAL STRESS; BETA-BLOCKERS; BLOOD-FLOW; DISEASE

Abstract

Endothelial dysfunction is more prevalent in African Americans (AAs) compared with whites. The authors hypothesized that nebivolol, a selective β1-antagonist that stimulates nitric oxide (NO), will improve endothelial function in AAs with hypertension when compared with metoprolol. In a double-blind, randomized, crossover study, 19 AA hypertensive patients were randomized to a 12-week treatment period with either nebivolol 10 mg or metoprolol succinate 100 mg 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 with metoprolol treatment (21% vs 12% reduction in FBF, P=.06, respectively). This difference was more significant after combined administration of L-NMMA and TEA (P<.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 with metoprolol in AAs with hypertension.