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Korean J Androl. 2002 Aug;20(2):75-81. Korean. Original Article.
Yang DY , Kim SY , Kim H , Hyun JS , Hellstrom WJ .
Department of Urology, Hallym University School of Medicine, Seoul, Korea.
Department of Urology, Gyeongsang National University School of Medicine, Chinju, Korea..
Department of Urology, Tulane University School of Medicine, New Orleans, Lousiana, USA.

PURPOSE: This study was designed to investigate the role of chronic endothelin receptor antagonism to preserve erectile function in diabetic rats. MATERIALS AND METHODS: Forty adult male Sprague-Dawley rats (250-350 gm) were divided into 4 groups: Group 1, non-diabetic control rats (n=5); Group 2, non-diabetic rats fed 10 mg/kg of RO-485695, a combined endothelin receptor antagonist (n=5); Group 3, diabetic control (n=15); Group 4, diabetic rats fed 10 mg/kg of RO-485695 (n=15). Streptozotocin, 65 mg/kg, was used for development of diabetes mellitus. Body weight and blood glucose levels were measured every 2 weeks and drug feeding was done by oral gavage. Twelve weeks after induction of diabetes and RO-485695 treatment, erectile function was determined by measurement of intracavernosal pressure (ICP) and maximal arterial pressure (MAP) after electrical stimulation of the cavernosal nerve. RT-PCR analysis for detection of mRNA of endothelin-1, endothelin receptor A (ET-A), and endothelin receptor B (ET-B), and Western blot analysis and immunohistochemical evaluation of the eNOS protein were performed. RESULTS: Body weight and blood glucose levels were not influenced by 10 mg/kg of RO-485695. Erectile function after 5 volts stimulation was significantly decreased in the diabetic rat (group 3 & 4) compared with the non-diabetic rat (group 1 & 2) (64.3+/-9.6 vs 41.9+/-14.8 mmHg), but increased in group 4 compared with group 3 (44.3+/-16.9 vs 36.6+/-10.1 mmHg). The mRNA expression of endothelin-1 was up-regulated significantly in group 3 & 4 when compared with group 1 & 2. However this endothelin expression was down-regulated in group 4 compared with group 3. The mRNA expression of ET-A among 4 groups was not significantly different. ET-B band in rat cavernosal tissue could not be observed in any group under these conditions. eNOS protein expression was increased in group 4 compared with group 3. CONCLUSIONS: Chronic endothelin receptor antagonism in the experimental diabetic rat model has been demonstrated to preserve cavernosal erectile function, suggesting a possible therapeutic role for endothelin receptor antagonists in diabetic erectile dysfunction.

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