The morphological changes after SHH inhibition were so extensive that they affected penile physiology and caused significant ED. We propose the hypothesis that decreased SHH signaling is a cause of ED in neurological models of impotence by increasing apoptosis in penile smooth muscle, which leads to morphological changes within the corpora cavernosal sinusoidal tissue, and thus to ED. This hypothesis is supported by previous observations of decreased SHH protein, smooth muscle and endothelium, significantly increased apoptosis, and erectile dysfunction in BB/WOR diabetic rats.
In this study we have examined a second model of ED, the bilateral CN-injured Sprague Dawley rat, in order to determine if decreased SHH signaling derived from the nerves is the cause of morphology changes (increased apoptosis, smooth muscle and endothelial degradation) which occur in the corpora cavernosa postprostatectomy, and to evaluate if SHH protein treatment of the penis can be used to prevent CN injury-induced apoptosis. In this study we have shown that the active form of SHH protein was significantly decreased following CN injury and that SHH treatment at the time of CN injury was able to prevent/postpone CN injury-induced apoptosis. These results show that SHH has significant potential to be developed as a treatment to prevent smooth muscle apoptosis in the penis postprostatectomy.