EFFECT OF EXPERIMENTAL HYPERCHOLESTEROLEMIA ON CAVERNOSAL STRUCTURES C ¸ ETIN YES ¸ILLI, O ¨ NDER YAMAN, AND KADRI ANAFARTA ABSTRACT Objectives. To determine the effect of experimental hypercholesterolemia on the ultrastructure of cavern- osal smooth muscle cells, endothelial cells, elastic fibers, and collagen content, which are the key structures fundamental for erection. Methods. Forty-two New Zealand white rabbits were divided into a control group (group 1, n = 7, fed a standard diet), a hypercholesterolemia group (group 2, n = 20, fed a diet containing 1% cholesterol for 8 weeks), and a reversibility group (group 3, n = 15, fed a 1% cholesterol diet for 8 weeks, then switched to a standard diet for 4 weeks). Blood samples were obtained for lipid determination before and after the study. The cavernosal tissues were obtained at the end of 8 weeks for groups 1 and 2 and at the end of 12 weeks for group 3 and immunohistochemical examinations of these cells were performed. Results. Immunohistochemical analysis revealed that hypercholesterolemia produces marked and revers- ible decreases in the cavernosal content of smooth muscle cells, endothelial cells, and elastic fibers and increases the content of collagen 3 and 4. Conclusions. Our findings suggest that hypercholesterolemia in this animal model affects the percentage of staining for smooth muscle actin, endothelial cells, elastin, and collagen 3 and 4. However, since this effect is temporary depending on the blood cholesterol levels, it might not alter the erectile function. UROLOGY 57: 1184–1188, 2001. © 2001, Elsevier Science Inc. E rectile dysfunction (ED) is a common disease, especially among aging men. The incidence of ED increases with age, from a rate of 5% for com- plete ED in men 40 years old to 15% in those 70 years old or older. 1 The incidence of organic ED is estimated at 50% to 80% of the organic etiologies; atherosclerosis is the most common cause of vas- culogenic impotence. 2 Cardiovascular disease and ED share many risk factors, including diabetes, smoking, hypertension, and hypercholesterol- emia. 3 It has been shown that these risk factors impair the endothelium-mediated relaxations of blood vessels both in experimental animals and humans. 4 The purpose of this study was to determine the effect of experimental hypercholesterolemia on the ultrastructure of cavernosal smooth muscle cells (SMCs), endothelial cells (ECs), elastic fibers (EFs), and collagen content, which are the key structures fundamental to erection. MATERIAL AND METHODS Forty-two male New Zealand white rabbits (mean age 6 to 7 months, weight 3 to 3.5 kg) comprised the study subjects. These rabbits were divided into three groups according to diet (100 g/day): group 1, control, 7 rabbits, fed standard rabbit chow for 8 weeks; group 2, hypercholesterolemia group, 20 rabbits fed a high-cholesterol diet (1% cholesterol) for 8 weeks; and group 3, reversibility group, 15 rabbits, fed stan- dard rabbit chow for 4 weeks after inducing hypercholesterol- emia with 8 weeks of the high-cholesterol diet. The 1% cholesterol diet was prepared by dissolving pure cholesterol (100%) in powdered form in water and then mix- ing it with standard rabbit chow in a 1% ratio. The diet was prepared weekly for each rabbit (700 g— 693 g of standard rabbit chow plus 7 g pure cholesterol). SERUM CHOLESTEROL DETERMINATION Blood samples were obtained from the central vein of the ear from all rabbits at baseline and at the end of 8 weeks. Addi- tional blood samples were obtained from the rabbits in group 3 at the end of 12 weeks— 4 weeks after feeding with standard rabbit chow. The total cholesterol levels were determined at the biochemistry laboratory of the University of Ankara School of Medicine. From the Department of Urology, Ankara University School of Medicine, Ankara, Turkey Reprint requests: O ¨ nder Yaman, M.D., S ¸ ehit Ersan cad. Pembe Ko ¨s ¸k Sitesi B. 1 Blok, No. 15, 06680, C ¸ ankaya, Ankara, Turkey Submitted: September 18, 2000, accepted (with revisions): Jan- uary 26, 2001 BASIC SCIENCE © 2001, ELSEVIER SCIENCE INC. 0090-4295/01/$20.00 1184 ALL RIGHTS RESERVED PII S0090-4295(01)00974-8