title: Nebivolol increases arterial distensibility in vivo.
abstract: Arterial stiffness is a key determinant of cardiovascular risk in hypertensive patients. beta-Blockers appear to be less effective than other drugs in improving outcome in hypertensive patients, and a potential explanation may be that beta-blockers are less effective in reducing arterial stiffness. The aim of this study was to assess the direct effect of beta-blockade on pulse wave velocity (PWV), a robust measure of arterial distensibility, using a local, ovine, hind-limb model. In addition, we hypothesized that the vasodilating beta-blocker nebivolol, but not atenolol, would increase arterial distensibility in vivo. All studies were conducted in anesthetized sheep. PWV was recorded in vivo using a dual pressure-sensing catheter placed in the common iliac artery. Intraarterial infusion of nebivolol reduced PWV by 6+/-3% at the higher dose (P<0.001), but did not alter mean arterial pressure (change of -1+/-3 mm Hg, P=0.1). In contrast, atenolol had no effect on PWV (P=0.11) despite a small drop in mean pressure (change of -5+/-3 mm Hg, P<0.01). Infusion of glyceryl trinitrate led to a dose-dependent fall in PWV, and 2 nmol/min produced a similar reduction in PWV to the higher dose of nebivolol (500 nmol/min). The effect of nebivolol on PWV was significantly attenuated during coinfusion of N(G)-monomethyl-L-arginine (P=0.003) and also during coinfusion of butoxamine (P=0.02). These results demonstrate that nebivolol, but not atenolol, increases arterial distensibility. This effect of nebivolol is mediated through the release of NO via a beta2 adrenoceptor-dependent mechanism. Thus, nebivolol may be of benefit in conditions of increased large artery stiffness, such as isolated systolic hypertension.
authors.affiliation: Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK. cmm41@cam.ac.uk
authors.forename: Carmel M
authors.initials: CM
authors.lastname: McEniery
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmitt
authors.forename: Ahmad
authors.initials: A
authors.lastname: Qasem
authors.forename: David J
authors.initials: DJ
authors.lastname: Webb
authors.forename: Alberto P
authors.initials: AP
authors.lastname: Avolio
authors.forename: Ian B
authors.initials: IB
authors.lastname: Wilkinson
authors.forename: John R
authors.initials: JR
authors.lastname: Cockcroft
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002078:Butoxamine / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply; D007083:Iliac Artery / Q000187:drug effects* / Q000502:physiology; D007261:Infusions, Intra-Arterial; D000068577:Nebivolol; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D005996:Nitroglycerin / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D018343:Receptors, Adrenergic, beta-2; D000068577:Nebivolol; D002078:Butoxamine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001262:Atenolol; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin