Expression of caveolin-1 in cavernous tissue on a denervated animal model and its modification with sildenafil.

Becher, E⁽¹⁾; Toblli, J⁽²⁾; Castronuovo, C⁽¹⁾; Nolazco, C⁽¹⁾; Rosenfeld, C⁽¹⁾; Grosman, H⁽³⁾; Vazquez, E⁽⁴⁾; Villar, ME⁽⁴⁾

⁽¹⁾Div. Urology, Hospital de Clinicas "José de San Martín". University of Buenos Aires. ⁽²⁾Laboratory of Experimental Medicine, Hospital Alemán. ⁽³⁾Dept. Clinical Biochemistry, School of Pharmacy and Biochemistry, University of Buenos Aires ⁽⁴⁾Dept. Biologic Chemistry, School of Sciences, University of Buenos Aires. Buenos Aires, Argentina.

Introduction: Radical pelvic surgery is a major cause of erectile dysfunction; it is related to the extent of the neural injury and might be influenced by early pharmacological intervention. Caveolae are specialized plasma membrane invaginations on the surface of most cells involved in endocytosis. Animal studies showed that aging and hypertension decreases trabecular SM/collagen ratio and as well as the concentration of caveolae and hence, a reduced expression of caveolin-1 (Cav-1), a caveolar protein present in cavernous tissue.
Objective: to determine de expression of Cav-1 as marker of cavernous tissue damage and to evaluate the impact of early sildenafil administration in animal models of partial and total penile denervation.
Methods: 36 adult Sprague-Dawley rats were divided into 6 groups (n:6) of bilateral, unilateral penile denervation and sham surgery with and without daily administration of 10 mg/kg of sildenafil.
The animals were killed 7 weeks after the procedure and corporal tissue was analyzed with western blotting and immunostaining with antibodies against Cav-1 and alpha-actin (standard marker).
Results: Mean values for Cav-1 and alpha-actin were: Bilat: C:1.4 A:3.9 (p<0.01 vs. all groups), Unilat: C:3.5 A:6.2 (p<0.01 vs. sham, unilat+s, sham+s), Sham: C:12.5 A:15.7 (p<0.01 vs. bilat+s, unilat+s), Bilat+S: C:4.7, A:7.2 (p<0.01 vs. unilat+s, sham+s), Unilat+S: C:8.0 A:10.6(p<0.01 vs. unilat+s, sham+s), Sham+S: C:13.2 A:14.5 (see table).
Conclusions: Expression of Cav-1 and alpha-actin in cavernous tissue is significantly reduced by pelvic nerve injury and is related to the extent of the neural damage. Early administration of sildenafil elicits a positive effect on Cav-1 expression, meaning cavernous tissue preservation, with a greater impact on animals with unilateral injury. In the future, the possibility of dosing Cav-1 in penile or peripheral blood could be useful as a marker of cavernous tissue health.

Tabla: Caveolin in cavernous smooth muscle. Positive staining area (%)