Nebivolol, but Not Metoprolol, Improves Endothelial Function of the Corpus Cavernosum in Apolipoprotein E-Knockout Mice

Abstract

To determine the effects and underlying mechanisms of treatment with the β-receptor blockers nebivolol and metoprolol on penile endothelial function in apolipoprotein E (ApoE)^-/- mice, wild-type (WT) and ApoE^-/- mice were fed with a cholesterol-rich diet for 7 weeks. ApoE^-/- mice were treated with nebivolol (10 mg/kg/day) or metoprolol (90 mg/kg/day). Endothelial function of aortic and corpora cavernosal tissue was assessed by pharmacological stimulation with carbachol (endothelium dependent) or glycerol trinitrate (endothelium independent) in organ bath experiments. Atherosclerotic lesion formation was evaluated with oil-red staining, and modulation of reactive oxygen species (ROS) production was determined with lipid peroxidation. Heart rate, but not blood pressure, was decreased in nebivolol- and metoprolol-treated ApoE^-/- mice (p < 0.01) compared with controls and WT mice without significant intergroup differences. Atherosclerotic lesion formation in the aortic root was increased in ApoE^-/- mice (p < 0.01) with a more significant improvement in nebivolol- (p < 0.01) compared with metoprolol-treated mice (p < 0.05). Endothelium-dependent relaxation of the corpora cavernosa was significantly impaired in ApoE^-/- mice (p < 0.05), which improved in nebivolol- versus metoprolol-treated mice. Efficacy of endothelium-dependent relaxation was comparable in aortic and penile tissue. Quantification of ROS production via lipid peroxidation revealed a significant reduction of superoxide anion production in nebivolol-treated (p < 0.05) but not metoprolol-treated mice compared with ApoE^-/- controls. Nebivolol improves penile endothelial function as a surrogate of erectile function in ApoE^-/- mice. These effects may be related to a reduction of ROS production, which is independent of heart rate reduction, because metoprolol did not increase endothelial function.