TY - JOUR
T1 - Nebivolol increases arterial distensibility in vivo
AU - McEniery, Carmel M.
AU - Schmitt, Matthias
AU - Qasem, Ahmad
AU - Webb, David J.
AU - Avolio, Alberto P.
AU - Wilkinson, Ian B.
AU - Cockcroft, John R.
PY - 2004/9
Y1 - 2004/9
N2 - Arterial stiffness is a key determinant of cardiovascular risk in hypertensive patients. β-Blockers appear to be less effective than other drugs in improving outcome in hypertensive patients, and a potential explanation may be that β-blockers are less effective in reducing arterial stiffness. The aim of this study was to assess the direct effect of β-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 β-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 NG-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 β2 adrenoceptor-dependent mechanism. Thus, nebivolol may be of benefit in conditions of increased large artery stiffness, such as isolated systolic hypertension.
AB - Arterial stiffness is a key determinant of cardiovascular risk in hypertensive patients. β-Blockers appear to be less effective than other drugs in improving outcome in hypertensive patients, and a potential explanation may be that β-blockers are less effective in reducing arterial stiffness. The aim of this study was to assess the direct effect of β-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 β-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 NG-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 β2 adrenoceptor-dependent mechanism. Thus, nebivolol may be of benefit in conditions of increased large artery stiffness, such as isolated systolic hypertension.
UR - http://www.scopus.com/inward/record.url?scp=3543005757&partnerID=8YFLogxK
U2 - 10.1161/01.HYP.0000137983.45556.6e
DO - 10.1161/01.HYP.0000137983.45556.6e
M3 - Article
C2 - 15262912
AN - SCOPUS:3543005757
VL - 44
SP - 305
EP - 310
JO - Hypertension
JF - Hypertension
SN - 0194-911X
IS - 3
ER -