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
| Autor: | Wen Ji Li, Soo Woong Kim, Kyong Shin Ryu, Jae-Seung Paick, Kwanjin Park |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Nephrology medicine.medical_specialty Programmed cell death Phosphodiesterase Inhibitors Urology Apoptosis Pyrimidinones Diabetes Complications Rats Sprague-Dawley Erectile Dysfunction Internal medicine Diabetes mellitus medicine Animals Sulfones Phosphodiesterase inhibitor Protein kinase B business.industry Muscle Smooth Phosphodiesterase 5 Inhibitors Streptozotocin medicine.disease Rats Disease Models Animal Endocrinology Erectile dysfunction business Proto-Oncogene Proteins c-akt Penis Signal Transduction medicine.drug |
| Zdroj: | European Urology. 53:1282-1289 |
| ISSN: | 0302-2838 |
| Popis: | 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.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.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, p0.05). 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.Chronic treatment with PDE5I activated Akt signalling, which suppressed pro-apoptotic stimuli and maintained erectile function in rat model of diabetic erectile dysfunction. |
| Databáze: | OpenAIRE |
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