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

Abstract

Introduction 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. Aim 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. Methods 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. Main Outcome Measures 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 α-smooth muscle actin (α-SMA) positive immunostaining per area and (ii) caveolin-1 expressed as a percentage of area. Results A marked decrease in both caveolin-1 and α-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. Conclusion Caveolin-1 and α-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.

Nitric Oxide-Induced Vasorelaxation in Response to PnTx2-6 Toxin from Phoneutria nigriventer Spider in Rat Cavernosal Tissue

“…Based on these data, the role of PnTx2-6 seems to act locally, not centrally. Improved cavernosal relaxation evoked by PnTx2-6 was found to be further increased in the presence of the PDE5 inhibitor, sildenafil ( Figure 6B), a common therapeutic strategy to treat ED [52,53]. Considering that PnTx2-6 increases NO bioavailability in penile tissue thus enhancing erectile function, and increasing cGMP levels augments this response, we speculate that PnTx2-6 toxin regulates penile function independent of PDE5.…”

The effects of combined free radical scavenger and sildenafil therapy on age-associated erectile dysfunction: An animal model

“…[42] Others have demonstrated reduced expression of caveolin-1 following pelvic nerve injury and have suggested the possibility of using caveolin-1 as a biomarker for cavernosal health. [4344]…”

Gas what: NO is not the only answer to sexual function

“…Alterations in caveolin‐1 expression were reported in different animal models such as decreased caveolin‐1 expression in diabetic, aged and nerve injured rats penis (Becher et al ., ) or increased caveolin‐1 mRNA expression in SHR and protein expression in hypercholesterolaemic rat penis (Bakircioglu et al ., ; Yono et al ., ). Investigating the role of caveolar domains in erectile function of these gasotransmitters may bring new targets for ED treatment.…”