Vardenafil Improves Penile Erection in Type 2 Diabetes Mellitus Patients with Erectile Dysfunction: Role of Tropomyosin
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2013
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Elsevier
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Zamorano-León JJ, Olivier C, de Las Heras N, Mateos-Cáceres PJ, Brime Menéndez R, Rodríguez-Sierra P, Martín Palacios N, Manso LS, Modrego J, Segura A, Macaya C, López-Farré AJ. Vardenafil improves penile erection in type 2 diabetes mellitus patients with erectile dysfunction: role of tropomyosin. J Sex Med. 2013 Dec;10(12):3110-20. doi: 10.1111/jsm.12324
Abstract
Introduction. Evidences have been suggested that phosphodiesterase type 5 (PDE5) inhibition promotes
vasculoprotective benefits in patients with cardiovascular diseases.
Aim. The aim of this study is to analyze the systemic effect of PDE5 inhibition in type 2 diabetes mellitus patients
with erectile dysfunction (ED) determining changes in the expression levels of plasma proteins.
Methods. Seventeen patients with controlled type 2 diabetes mellitus and ED were included in the study. Patients
received vardenafil hydrochloride 20 mg on demand during 12 weeks. At the beginning and 12 weeks after vardenafil
administration, plasma samples were collected and analyzed using proteomics.
Main Outcome Measures. International Index of Erectile Function-Erectile Function Domain (IIEF-EFD) and
plasma protein expression before and after vardenafil administration. Nitrate/nitrite release, PDE5, and soluble
guanylate cyclase (sGC) expression and cyclic guanosine monophosphate (cGMP) content in cultured bovine aortic
endothelial cells (BAECs).
Results. The IIEF-EFD score was markedly improved after 12 weeks of vardenafil administration. Plasma levels of
alpha 1-antitrypsin isotypes 4 and 6 and β-tropomyosin were decreased, whereas apolipoprotein AI isoype 5 was
increased 12 weeks after vardenafil administration. Only β-tropomyosin plasma levels were inversely correlated with
IIEF-EFD score. Tropomyosin has been added to cultured BAECs and after 24 hours reduced the protein expression
level of sGC-β1 subunit and decreased the cGMP content. Tropomyosin did not modify PDE5 expression and nitric
oxide release in BAECs as compared with control BAECs. Vardenafil (10 μg/mL) did not modify sGC-β1 subunit
expression in tropomyosin + vardenafil-incubated BAECs; however, vardenafil significantly reversed the reduction of
cGMP content induced by tropomyosin.
Conclusion. Vardenafil administration improved erectile functionality in controlled type 2 diabetes mellitus patients
with ED, which was associated with reduction of circulating plasma β-tropomyosin levels. Tropomyosin affected by
itself the cGMP generating system suggesting a possible new mechanism involved in ED. Vardenafil reversed the
reduction effect of cGMP content elicited by tropomyosin in BAECs. Zamorano-León JJ, Olivier C, de las Heras
N, Mateos-Cáceres PJ, Brime Menéndez R,Rodríguez-Sierra P, Martín Palacios N, Manso LSJ, Modrego J,
Segura A, Macaya C, and López-Farré AJ. Vardenafil improves penile erection in type 2 diabetes mellitus
patients with erectile dysfunction: Role of tropomyosin. J Sex Med 2013;10:3110–3120.