Nebivolol is more effective than atenolol for blood pressure variability attenuation and target organ damage prevention in L-NAME hypertensive rats

Abstract

β-Adrenergic blockers are no longer recommended as first-line therapy due to the reduced cardioprotection of traditional β-blockers compared with other antihypertensive drugs. It is unknown whether third-generation β-blockers share the limitations of traditional β-blockers. The aim of the present study was to compare the effects of nebivolol or atenolol on central and peripheral systolic blood pressure (SBP) and its variability and target organ damage (TOD) in N-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. Male Wistar rats were treated with L-NAME for 8 weeks together with oral administration of nebivolol 30 mg/kg (n = 8), atenolol 90 mg/kg (n = 8), or vehicle (n = 8). The control group was composed of vehicle-treated Wistar rats. SBP and its variability, as well as echocardiographic parameters, were assessed during the last 2 weeks of treatment. Tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor β (TGF-β), and histopathological parameters were evaluated in the left ventricle and aorta. Nebivolol had a greater ability than atenolol to decrease central SBP and mid-term and short-term blood pressure variability (BPV) in L-NAME rats. Echocardiographic analysis showed that nebivolol was more effective than atenolol on E/A wave ratio normalization. Compared with atenolol treatment, nebivolol had a greater protective effect on different TOD markers, inducing a decrease in collagen deposition and a reduction in the proinflammatory cytokines IL-6 and TNF-α in the left ventricle and aorta. Our findings suggest that the adverse hemodynamic profile and the reduced cardiovascular protection reported with traditional β-blockers must not be carried forward to third-generation β-blockers.