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Tadalafil increases Akt and extracellular signal-regulated kinase 1/2 activation, and prevents apoptotic cell death in the penis following denervation

Lysiak JJ, Yang SK, Klausner AP, Son H, Tuttle JB, Steers WD

The Journal of urology, 2008

Abstract

PURPOSE: Despite techniques to preserve the cavernous nerves during radical prostatectomy erectile dysfunction remains a complication. We determined whether bilateral cavernous nerve resection induces apoptosis in the penis. We also determined whether treatment with the phosphodiesterase-5 inhibitor tadalafil prevents apoptosis as well as the specific mechanisms involved.

MATERIALS AND METHODS: Mice were subjected to cavernous nerve resection or sham surgery. Penises were processed for the identification of apoptotic cells, changes in phosphorylation of several protein kinases and immunolocalization of specific kinases. Mice were also placed on tadalafil or vehicle after cavernous nerve resection and the penises were processed as described. Statistical analysis was performed with the Mann-Whitney U test for comparisons among groups or Student's t test.

RESULTS: An increase in apoptotic cavernous smooth muscle and endothelial cells was evident by 2 weeks, which further increased 4 and 6 weeks after cavernous nerve resection. Apoptosis coincided with an increase in the phosphorylation of c-jun N-terminal kinase and p38 mitogen activated protein kinase. Phospho-c-jun N-terminal kinase was immunolocalized to endothelial and smooth muscle cells. Treatment with tadalafil decreased the number of apoptotic cells and increased the phosphorylation of the 2 survival associated kinases Akt and extracellular signal-regulated kinase 1/2.

CONCLUSIONS: These results provide a rationale for…

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