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KMID : 0356420020200020075
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Journal of Korean Andrology
2002 Volume.20 No. 2 p.75 ~ p.81
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The Role of Chronic Endothelin Antagonism for Preserving Erectile Function in Experimental Diabetic Rats
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Yang Dae-Yul
Kim Sung-Yong
Kim Ha-Young
Hyun Jae-Seog
Hellstrom Wayne J.G.
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Abstract
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B>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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KEYWORD
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Endothelins, Diabetes mellitus, Corpus cavernosum
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