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Chronic treatment with a type 5 phosphodiesterase inhibitor suppresses apoptosis of corporal smooth muscle by potentiating Akt signalling in a rat model of diabetic erectile dysfunction

Cited 38 time in Web of Science Cited 34 time in Scopus
Authors
Park, Kwanjin; Ryu, Kyong Shin; Li, Wen Ji; Kim, Soo Woong; Paick, Jae-Seung
Issue Date
2008-02-05
Publisher
Elsevier
Citation
Eur Urol. 2008;53(6):1282-1288
Keywords
AnimalsApoptosis/*drug effectsCyclic Nucleotide Phosphodiesterases, Type 5/*antagonists & inhibitorsDiabetes Complications/*drug therapyDisease Models, AnimalErectile Dysfunction/*drug therapy/etiologyMaleMuscle, Smooth/*drug effectsPenis/*drug effectsPhosphodiesterase Inhibitors/*pharmacologyProto-Oncogene Proteins c-akt/*drug effects/*physiologyPyrimidinones/*pharmacologyRatsRats, Sprague-DawleySignal TransductionSulfones/*pharmacology
Abstract
OBJECTIVES: To examine whether chronic treatment with a type 5 phosphodiesterase inhibitor (PDE5I) could suppress corporal apoptosis via potentiation of Akt signalling in diabetic erectile dysfunction. METHODS: Sprague-Dawley rats (12 wk old) were divided into three groups (n=12 in each): normal control, diabetes (DM), and diabetes treated with PDE5I (DM+PDE5I). The rats in the diabetic groups received a single injection of streptozotocin (50mg/kg), and from 8 wk after establishment of diabetes, DM and DM+PDE5I were treated with vehicle and PDE5I (SK-3530, 10mg/kg), respectively, for 4 wk. After 12 wk of streptozotocin injections, six rats in each group underwent cavernosometry with cavernous nerve electrostimulation (2V, 0.2 ms, 50s, 2.5-20 Hz). The penile tissues from the remaining six rats were used for immunohistochemical evaluation of apoptosis, immunoblotting for the phosphorylation of Akt and its downstream molecule Bad, and a colorimetric assay of caspase activity. RESULTS: Rats in the DM group showed markedly lower erectile parameters than those in the control group, whereas rats in the DM+PDE5I group showed normalized results. Despite persistent hyperglycaemia, PDE5I treatment significantly reduced the mean apoptotic index (39.6+/-4.6 vs. 21.3+/-1.7, p<0.05). Densitometry revealed significantly higher levels of Akt and Bad phosphorylation, implying inhibition of pro-apoptotic stimuli. PDE5I treatment also significantly inhibited the activities of cavernosal caspase 3 and caspase 9, the main effectors of apoptosis. CONCLUSIONS: Chronic treatment with PDE5I activated Akt signalling, which suppressed pro-apoptotic stimuli and maintained erectile function in rat model of diabetic erectile dysfunction.
ISSN
0302-2838 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18243503

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6X10-4RN46JR-1-B&_cdi=7228&_user=168665&_orig=search&_coverDate=06%2F30%2F2008&_sk=999469993&view=c&wchp=dGLzVtb-zSkWb&md5=d6712149523b8ac3f1cfd4a5e42224f4&ie=/sdarticle.pdf

http://hdl.handle.net/10371/68089
DOI
https://doi.org/10.1016/j.eururo.2008.01.032
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College of Medicine/School of Medicine (의과대학/대학원)Urology (비뇨기과학전공)Journal Papers (저널논문_비뇨기과학전공)
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