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

被引:35
作者
Ahn, GJ
Yu, JY
Choi, SM
Kang, KK
Ahn, BO
Kwon, JW
Kang, SK
Lee, BC
Hwang, WS
机构
[1] Dong A Pharmaceut Co, Res Inst, Yongin 449905, Kyunggi, South Korea
[2] Seoul Natl Univ, Coll Vet Med, Dept Theriogenol, Seoul, South Korea
来源
INTERNATIONAL JOURNAL OF ANDROLOGY | 2005年 / 28卷 / 05期
关键词
DA-8159; diabetic rat; endothelial dysfunction; intracoporal pressure; phosphodiesterase type 5 inhibitor;
D O I
10.1111/j.1365-2605.2005.00537.x
中图分类号
R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
摘要
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 < 0.05). At the 5 Hz frequency, DA-8159 10 mg/kg also induced a significant increase in the AUC compared with the diabetic control. The maximum ICP/MAP ratio (%) of the 10 mg/kg treatment group was significantly higher in both the 10 Hz and 5 Hz frequency groups ( p < 0.05). A treatment of 3 mg/kg tended to increase the AUC and peak ICP/MAP but was not statistically significant. The Ach EC50 value of the diabetic group was significantly higher than in the normal control (120.50 +/- 22.90 nM vs. 86.80 +/- 9.30 nM, respectively), and 10 mg/kg treatment group showed a significantly lower EC50 value (88.38 +/- 19.7 nM). The ET-1 level was lower in groups treated with DA- 8159, 3 mg/kg and 10 mg/kg treatment induced a statistical difference compared with the diabetic control ( 1.15 +/- 0.34 fmol/mL vs. 2.51 +/- 0.55 fmol/mL, respectively, p < 0.05). These results demonstrate that chronic administration of DA-8159 could attenuate the development of the ED in diabetes and its effect is associated with an improvement in the endothelial function.
引用
收藏
页码:260 / 266
页数:7
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