Expression of Caveolin-1 in Penile Cavernosal Tissue in a Denervated Animal Model after Treatment with Sildenafil Citrate

Abstract

Radical pelvic surgery is a major cause of erectile dysfunction due to iatrogenic cavernous nerve damage. Endothelial nitric oxide synthase, which generates nitric oxide (NO) in the cavernosal tissues, localizes to specialized plasma membrane invaginations known as caveolae. Growing evidence suggests that caveolae are major components of signal trafficking and that stimuli that affect the concentration of the main structural protein of caveolae, caveolin-1 influence NO signaling. To evaluate caveolin-1 expression as a marker of cavernous tissue damage and determine the impact of early sildenafil administration on caveolin-1 expression in animal models of partial and total surgical penile denervation. Thirty-six rats were divided into six groups (N = 6 per group) that received bilateral or unilateral penile denervation or sham surgery, with and without sildenafil 10 mg daily for 7 weeks. Sections were taken from the proximal middle portion of the penis of all animals. Cavernous tissue was delineated by the tunica albuginea, then the extent of immunostaining for the following parameters was quantitated to determine (i) cavernous smooth muscle layer in the cavernous space expressed as the percentage of alpha-smooth muscle actin (alpha-SMA) positive immunostaining per area and (ii) caveolin-1 expressed as a percentage of area. A marked decrease in both caveolin-1 and alpha-SMA expression in cavernous smooth muscle tissue and in the endothelium of rats was noted after a bilateral and unilateral neurotomy. Specimens from animals receiving sildenafil exhibited higher mean immunostaining values for both proteins in cavernous tissue. The differences were statistically significant compared with groups receiving the same surgical treatment without sildenafil. Caveolin-1 and alpha-SMA expression in cavernous tissue is significantly reduced by pelvic nerve injury, and the loss is related to the extent of the neural damage. Early administration of sildenafil elicits caveolin-1 expression, which appears to preserve cavernous tissue.