Nebivolol Increases Arterial Distensibility In Vivo

Abstract

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 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 β 2 adrenoceptor–dependent mechanism. Thus, nebivolol may be of benefit in conditions of increased large artery stiffness, such as isolated systolic hypertension.