Expression of caveolin-1 in penile cavernosal tissue in a denervated animal model after treatment with sildenafil citrate.

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 alpha-smooth muscle actin (alpha-SMA) positive immunostaining per area and (ii) caveolin-1 expressed as a percentage of area. RESULTS: 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. CONCLUSION: 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.

The effect of different antihypertensive drugs on cavernous tissue in experimental chronic renal insufficiency.

BACKGROUND: Male erectile dysfunction increases in prevalence in patients with severe chronic renal failure. Since arterial hypertension induces significant damage in cavernous tissue (CT), and considering that hypertension is extremely common in patients with end-stage renal disease (ESRD), the aim of this study was to evaluate the effect of the most conventionally employed antihypertensive drugs on CT in a rat model of renal insufficiency. METHODS: Five groups of male rats with subtotal nephrectomy (STNx) and 1 with sham operations were studied over 6 months: STNx without treatment, STNx with benazepril (BZ), STNx with losartan (LS), STNx with amlodipine (AML) and STNx with atenolol (AT) plus the sham group. All rats were sacrificed at 6 months after STNx, and penises processed for LM and immunohistochemical studies. Cavernous smooth muscle (CSM) and vascular smooth muscle (VSM) from cavernous arteries and the amount of collagen type III were evaluated. RESULTS: All groups with antihypertensive drugs showed similar control in blood pressure throughout the study. Un-treated STNx, STNx with AML and STNx with AT presented significant (p<0.01) hypertrophy in both VSM and CSM, together with an increased amount of collagen type III in CT. Conversely, STNx with either BZ or LS showed a substantial (p<0.01) reduction in all of these variables, with values not different from the sham group. There was a significant (p<0.01) negative correlation between creatinine clearance and the amount of VSM, CSM and collagen type III deposition in CT in untreated STNx, STNx with AML and STNx with AT, but not in STNx with BZ, STNx with LS and sham. CONCLUSION: These results suggest that the interactions against the renin-angiotensin system (RAS) either by ACE inhibitors or angiotensin AT1 receptor blockers produce considerable benefits regarding structural abnormalities in CT in this animal model of renal insufficiency beyond blood pressure control.

[Modified laparoscopic scissors: a new instrument for performing endopyelotomy]. / Tijera laparoscópica modificada: un nuevo instrumento para realizar endopielotomía.

OBJECTIVE: The safety and success of antegrade endopyelotomy in the treatment of ureteropelvic junction (UPJ) stenosis have been documented in numerous literature reports over the last decade. We show a new available alternative to the way incision is performed. METHODS: Endopyelotomy with modified laparoscopic scissors was performed in 18 patients; 12 presented with primary obstruction and 6 with secondary obstruction. 3 mm laparoscopic scissors with one end sharpened and adapted for this technique are introduced through a nephroscope. A small puncture through the renal pelvis wall is made in the posterolateral position using the scissors' end. After that, scissors are opened under permanent endoscopic control as far as to visualization of the peripyelic space, continuing then with the internal edge of the scissors down to the UPJ. Visual control allowed us to coagulate any vessel and to avoid the bigger calibre ones. At the end of the procedure an endopyelotomy stent was placed over the safety guide wire. RESULTS: Results were good in 17 patients (94%); symptomatic relief and adequate pass of contrast to proximal ureter were observed in the remaining case, although pyelocalicilar dilation was not improved. Three vessels adjacent to the UPJ (16.6%) were discovered through the performed pyelotomy incision. Operative times were lower than 2 hours. Blood losses were minimal and patient recovery uneventful allowing hospital discharges within 48 hours. CONCLUSIONS: To use 3 mm laparoscopic scissors allows to perform endopyelotomy without changing endoscopes, precisely cutting due to retroperitoneum visualisation, and offers the chance to coagulate small calibre vascular elements and to avoid those of bigger size.