INVESTIGATIVE UROLOGY

Long-Term Effect of Experimental Hypercholesterolemia on Cavernosal Tissues
Karaboga R, Kilic O, Yaman O, Percinel S, Anafarta K
Department of Urology, Ankara University Medical Faculty, Ankara, Turkey
Urology. 2006; 67: 431-4

• Objectives: To determine the effect of long-term experimental hypercholesterolemia on cavernosal tissues and to evaluate whether these alterations are reversible after improvement of hypercholesterolemia.
• Methods: Thirty-seven New Zealand male rabbits with a mean age of 5 to 6 months and a weight of 2 to 2.5 kg were included in this study. The control group (group 1, n = 7) was fed with normal standard rabbit chow for 24 weeks, the hypercholesterolemia group (group 2, n = 17) was fed with a 1% pure cholesterol diet for 24 weeks, and the reversibility group (group 3, n = 13) was fed first with the 1% pure cholesterol diet for 24 weeks and then with normal standard rabbit chow for 12 weeks. The basal and 24-week serum lipid profiles of all groups and the 36-week serum lipid profiles of group 3 were measured. Core tissue samples 4 mm in diameter taken from formalin-fixed, paraffin-embedded tissue blocks of rabbit corpus cavernosum were examined for Masson trichrome histochemically and desmin and smooth muscle actin by the tissue array method using immunohistochemistry.
• Results: Hypercholesterolemia was observed in groups 2 and 3 at 24 weeks compared with group 1. In group 3, at 36 weeks, the cholesterol levels were decreased. A statistically significant (P < 0.05) irreversible decrease was observed in smooth muscle actin level in group 3 (reversibility group) by immunohistochemical analysis. The decrease in desmin was reversible, and no significant difference was observed in collagen among the three groups.
• Conclusions: Long-term chronic effects of experimental hypercholesterolemia on cavernosal smooth muscles might be irreversible and this might alter erectile function.
  
  
• Editorial Comment
  Conditions associated with altered function of nerves and endothelium, such as hypertension, smoking, hypercholesterolemia, diabetes, etc. may cause circulatory and structural changes in the penile erectile tissue and can result in arterial insufficiency and impaired smooth muscle relaxation (1). Hypercholesterolemia is considered one of the main risk factors of cardiovascular diseases and also for vasculogenic erectile dysfunction. It was demonstrated more than 5 years ago that hypercholesterolemia may cause impairment of endothelium-dependent relaxation and that oxidized LDL is the major causative cholesterol of the impaired relaxation response (2). The vascular endothelial growth factor (VEGF), which is an angiogenic growth factor and an endothelial cell-specific mitogen, and whose actions are coupled to nitric oxide, is probably involved in this kind of injury, because it was found that intracavernosal injections of VEGF appear to protect corporal endothelium from hypercholesterolemia induced injury, preserving endothelial dependent corporal smooth muscle relaxation in hypercholesterolaemic rabbit (3). Recently, it was found a significantly lower in vivo and in vitro erectile response to phosphodiesterase-5 inhibition in hypercholesterolaemic rabbits than in controls (4).
  The effect of experimental hypercholesterolemia on the ultrastructure of cavernosal smooth muscle cells, endothelial cells, elastic fibers, and collagen, which are the key structures for erection, were morphologically analyzed in hypercholesterolaemic rabbits, 5 years ago, by the same research group of the present paper (5). The findings shown that hypercholesterolemia in this animal model affect the percentage of staining for smooth muscle actin, endothelial cells, elastin, and collagen III and IV. However, the authors stated that this effect is temporary depending on the blood cholesterol levels, and, therefore, might not alter the erectile function.
  The present study, by Karaboga et al., is very much important because demonstrates by the first time, in our knowledge, that the long-term chronic effects of experimental hypercholesterolemia on cavernosal smooth muscles might be irreversible and therefore might alter erectile function.

References
1. Andersson KE: Erectile physiological and pathophysiological pathways involved in erectile dysfunction. J Urol. 2003; 170(2 Pt 2): S6-13; discussion S13-4.
2. Kim SC: Hyperlipidemia and erectile dysfunction. Asian J Androl. 2000; 2: 161-6.
3. Henry GD, Byrne R, Hunyh TT, Abraham V, Annex BH, Hagen PO, Donatucci CF: Intracavernosal injections of vascular endothelial growth factor protects endothelial dependent corpora cavernosal smooth muscle relaxation in the hypercholesterolemic rabbit: a preliminary study. Int J Impot Res. 2000; 12: 334-9.
4. Firoozi F, Longhurst PA, White MD: In vivo and in vitro response of corpus cavernosum to phosphodiesterase-5 inhibition in the hypercholesterolaemic rabbit. BJU Int. 2005; 96: 164-8. Comment in: BJU Int. 2005; 96: 1424.
5. Yesilli C, Yaman O, Anafarta K: Effect of experimental hypercholesterolemia on cavernosal structures. Urology. 2001; 57: 1184-8.

Dr. Francisco Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil