Nebivolol induces eNOS activation and NO-liberation in murine corpus cavernosum.
Erectile function is critically dependent upon the activation of the endothelial nitric oxide synthase (eNOS) in the smooth muscle cells of penile corpus cavernosum tissue. Nebivolol is a beta(1)-selective beta-adrenoceptor blocker (beta-ARB) with additional vasodilating properties, which have been attributed to eNOS-activation. Our study investigated whether nebivolol is able to increase eNOS activity in erectile tissue. Murine penile tissue was incubated in an organ bath under control conditions and in the presence of nebivolol or metoprolol. Immunofluorescence staining was performed using specific antibodies against eNOS-activation or eNOS-serine 1177 phosphorylation. Corpus cavernosum smooth muscle tissue was identified using a smooth muscle actin antibody. In addition, slices of murine erectile tissue were incubated with diaminofluorescein (DAF), a specific fluorescence marker for NO-liberation. Under control conditions and after application of metoprolol, we observed a small eNOS-activation and serine 1177-phosphorylation in murine corpus cavernosum tissue. A significant increase in eNOS-activation and serine 1177-phosphorylation of eNOS was observed only in the presence of nebivolol (10 muM). These alterations of the eNOS protein induced after application of nebivolol were associated with a time-dependent increase in DAF fluorescence in murine erectile tissue. We conclude that beta-adrenoceptor blockers differentially influence erectile tissue. Since cardiovascular diseases are often associated with the development of erectile dysfunction, the nebivolol-induced eNOS-activation in corpus cavernosum may be beneficial when treating patients suffering from cardiovascular disease.
Reidenbach
C
C
Department of Molecular and Cellular Sport Medicine, Institute of Cardiology and Sport Medicine, German Sport University Cologne, Cologne, Germany.
Schwinger
R H G
RH
Steinritz
D
D
Kehe
K
K
Thiermann
H
H
Klotz
T
T
Sommer
F
F
Bloch
W
W
Brixius
K
K
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects*; D007172:Erectile Dysfunction / Q000188:drug therapy*; D004983:Ethanolamines / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005470:Fluorometry; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000378:metabolism*; D000068577:Nebivolol; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D010413:Penis / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse