EXPRESSION OF CAVEOLIN-1 AND HEME-OXYGENASE-1 IN CAVERNOUS TISSUE OF SPONTANEOUS HYPERTENSIVE RATS: INFLUENCE OF SILDENAFIL CITRATE

MAZZA OSVALDO; TOBLLI JORGE; SACCA PAULA; GROSMAN HALINA; CASTRONUOVO CYNTHIA; BECHER E; VAZQUEZ ELBA

El Cairo, Egipto

Congreso; 12 Congreso Mundial de la Sociedad Internacional de la Medicina Sexual (ISSM; 2006

Sociedad Internacional de Medicina Sexual

AIM: Caveolae are specialized plasma membrane invaginations on the surface of most cells. Caveolin-1, which is a membrane-protein associated with caveolae and trans-Golgi network derived vesicles, is present in smooth muscle (SM) in the erectile tissue. Furthermore, the localization of heme degradation enzymes on plasma membrane caveolae presents a novel evidence that caveolin-1 interacts and modulates heme oxygenase1 HO-1 activity. Some studies in old rats indicate that aging decreases trabecular SM/collagen ratio and reduces expression of caveolin-1, consequently it may contribute to erectile dysfunction. It is currently accepted that spontaneous hypertensive rats (SHR) present morphological changes in the erectile tissue. This remodelling in erectile structures is not only in the interstitium but also in SM from vessels and cavernous spaces. Therefore, the purpose of this study is to evaluate whether SHR presents an altered expression of caveolin-1 and heme oxygenase isoforms due to the pathologic remodeling induced by arterial hypertension in the vascular bed and in the cavernous space, and secondary, whether sildenafil citrate plays a protective role on these structures.   METHODS: Twelve-week-old SHR (n=16) and control Wistar-Kyoto (WKY) rats (n=16), during four months 1) SHR (n=8) without treatment; 2) SHR with sildenafil citrate (n=8); 3) WKY without  treatment (n=8); and 4) WKY with sildenafil citrate. Sildenafil citrate 10 mg/Kg/day is administered in drinking water. At the end of the experiment, all the rats are killed. The penises are rapidly excised, and harvested at 0ºC for western blot analysis of caveolin-1 (anti-caveolin 1, BDTransduction Lab, San Diego, CA, USA) and HO-1 (anti-heme oxygenase 1, Stressgen, Victoria, BC, Canada). The intensity of bands of immunoblocks are quantified by densitometry.   RESULTS:  Turkey-Kramer Multiple Comparison Test   Groups                       N                     Caveolin-1                  HO-1                                                             Mean ± SD                 Mean ± SD _________________________________________________________      1) SHR                        8                      1.5   ±  0.3                   1.1 ±    0.3 2) SHR + S                 8                      1.1   ±  0.3                   0.9 ±    0.2 3) WKY                      8                      6.1   ± 0.7                   4.5 ±    0.4 4) WKY + S               8                      2.4   ± 0.4                   1.6 ±    0.3   WKY vs SHR, SHR+S and WKY+S (p0.05)                       CONCLUSION: Caveolin-1 and HO-1 are both significantly higher in WKY versus SHR. These alterations in Caveolin-1 and HO-1 observed in SHR can be an early expression of the aging process caused by high blood pressure. Sildenafil citrate fails in modifying the low expression of these two proteins