The Effects of Beta-blockers on Endothelial Nitric Oxide Synthase Immunoreactivity in the Rat Corpus Cavernosum

ObjectivesTo explain the mechanism of the effects of β-blockers on endothelial dysfunction and release of nitric oxide from the endothelium.MethodsA total of 72 Sprague-Dawley rats were divided into 9 different groups as follows: group 1: control (n = 10), group 2: metoprolol (Beloc) 100 mg/kg/d (n = 7), group 3: carvedilol (Dilatrend) 50 mg/kg/d (n = 7), group 4: nebivolol (Vasoxen) 10 mg/kg/d (n = 6), group 5: estrogen receptor (ER) antagonist ICI 182.780 (Fluvestrant) 50 μg/g (n = 10), group 6: nebivolol+ER antagonist (n = 8), group 7: androgen receptor (AR) antagonist (flutamide) 20 mg/kg (n = 7), group 8: nebivolol+AR antagonist (n = 7), and group 9: DMSO (solvent for ER antagonist) (n = 10). All β-blockers were applied with gastric gavage after dilution with 5 mL of serum physiological; ER and AR were both applied intraperitoneally (i.p.) for 14 days. In the isolated rat cavernous tissues, endothelial nitric oxide synthase (eNOS) and ER and AR immunoreactivity were analyzed quantitatively. One-way analysis of variance and Tukey test were used for statistical analysis.ResultsAlthough increased eNOS immunoreactivity was observed with nebivolol and nebivolol-flutamide in endothelial cells laying cavernous tissue, a lower score was observed after ICI-182.780 application, when compared with control cases. AR immunoreactivity in cavernosal endothelium was clearly higher with nebivolol. Higher H score and ER immunoreactivity were observed in the cavernous endothelium and smooth muscles in the nebivolol, carvedilol, and metoprolol groups when compared with control cases.ConclusionsWe showed that eNOS activity was increased in the nebivolol and nebivolol-flutamide groups, whereas it was decreased in the ICI 182.780 group. We believe that an ER-dependent mechanism triggered by nebivolol played a role in nitric oxide formation.