The effects of beta-blockers on endothelial nitric oxide synthase immunoreactivity in the rat corpus cavernosum.
OBJECTIVE
To explain the mechanism of the effects of beta-blockers on endothelial dysfunction and release of nitric oxide from the endothelium.


METHODS
A 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 microg/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 beta-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.


RESULTS
Although 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.


CONCLUSIONS
We 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.
Dogru
Mehmet Tolga
MT
Department of Cardiology, Faculty of Medicine, University of Kirikkale, Turkey.
Aydos
Tolga Reşat
TR
Aktuna
Zuhal
Z
Korkusuz
Petek
P
Zeybek
Dilara
D
Görgü
Nart
N
Korkut
Oğuzhan
O
Basar
Mehmet Murad
MM
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004727:Endothelium / Q000187:drug effects / Q000201:enzymology; D008297:Male; D019001:Nitric Oxide Synthase / Q000276:immunology*; D010413:Penis / Q000187:drug effects* / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000502:physiology; D011960:Receptors, Estrogen / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D019001:Nitric Oxide Synthase