Chronic administration of phosphodiesterase 5 inhibitor improves erectile and endothelial function in a rat model of diabetes

• Published in: International journal of andrology 2005-10, Vol.28 (5), p.260-266
• Main Authors: AHN, GOOK JUN, YU, JAE YOUNG, CHOI, SEUL MIN, KANG, KYUNG KOO, AHN, BYOUNG OK, KWON, JONG WON, KANG, SUNG KEUN, LEE, BYEONG CHUN, HWANG, WOO SUK
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Aorta, Thoracic - drug effects; Biological and medical sciences; Blood Pressure - drug effects; Cyclic Nucleotide Phosphodiesterases, Type 5; DA-8159; Diabetes Mellitus, Experimental - physiopathology; Diabetes. Impaired glucose tolerance; diabetic rat; Electric Stimulation; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; endothelial dysfunction; Endothelin-1 - metabolism; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fundamental and applied biological sciences. Psychology; Gynecology. Andrology. Obstetrics; intracoporal pressure; Male; Male genital diseases; Mammalian male genital system; Medical sciences; Penile Erection - drug effects; Phosphodiesterase Inhibitors - administration & dosage; Phosphodiesterase Inhibitors - therapeutic use; phosphodiesterase type 5 inhibitor; Phosphoric Diester Hydrolases - metabolism; Pyrimidines - administration & dosage; Pyrimidines - therapeutic use; Rats; Rats, Sprague-Dawley; Sulfonamides; Vasodilation - drug effects; Vertebrates: reproduction
• ISSN: 0105-6263; 1365-2605
• DOI: 10.1111/j.1365-2605.2005.00537.x

Summary This study was conducted to determine if the long‐term administration of the phosphodiesterase type 5 (PDE 5) inhibitor, DA‐8159, to diabetic rats can ameliorate the development of erectile dysfunction (ED) and endothelial dysfunction. After inducing diabetes with streptozotocin, DA‐8159 was orally administered at a dose of 3 mg/kg or 10 mg/kg for 8 weeks. To examine the effect on erectile response, electrostimulation of the cavernous nerve with the parameters of 3 V, 5 ms, 5 Hz or 10 Hz, was performed to measure the intracavernous pressure (ICP) and mean arterial pressure (MAP). Thoracic aorta relaxation in vitro was evaluated by adding acetycholine (Ach) cumulatively to the bathing medium. In addition, the plasma endothelin‐1 (ET‐1) levels were measured in order to investigate the effect of DA‐8159 on endothelial dysfunction. The area under the curve (AUC) from the ICP/MAP ratio in the 10 Hz stimulation showed a significantly increased AUC after the 10 mg/kg treatment compared with the diabetic group (8891 ± 619 vs. 6316 ± 1016, respectively, p