Ghasemi Mehdi, Sadeghipour Hamed, Asadi Shahrzad, Dehpour Ahmad Reza
Department of Pharmacology, School of Medicine, Medical Sciences / University of Tehran, PO Box: 13145-784, Tehran, Iran.
Life Sci. 2007 Sep 1;81(12):960-9. doi: 10.1016/j.lfs.2007.06.020. Epub 2007 Jul 3.
The purpose of the present study was to investigate the relaxant responses to the ATP-sensitive potassium (K(ATP)) channel opener cromakalim in corpus cavernosum strips from 1-, 2-, 4-, 6-, and 8-week streptozocin-induced diabetic rats. Cromakalim (1 nM-0.1 mM) produced concentration-dependent relaxation in phenylephrine (7.5 microM)-precontracted isolated rat corporal strips. Compared with age-matched control animals, a significant enhancement in cromakalim-induced relaxation of corpus cavernosum was observed in 2-week diabetic animals, whereas the relaxant responses to cromakalim were decreased in 6-and 8-week diabetic animals. However, the cromakalim-induced relaxation was not altered in either 1-week or 4-week rat corporal strips in comparison with corresponding age-matched non-diabetic groups. Preincubation with the K(ATP) channel blocker glibenclamide (10 microM) significantly inhibited the cromakalim-induced relaxation in both non-diabetic and diabetic rat corpus cavernosum, but neither the voltage-dependent K(+) channel (K(V)) antagonist 4-aminopyridine (1 mM) nor the calcium-activated K(+) channel (K(Ca)) antagonist charybdotoxin (0.1 microM) had significant effect on cromakalim-induced relaxation in both control and diabetic rat corporal strips. Relaxation responses to the nitric oxide donor sodium nitroprusside (1 nM-0.1 mM) in diabetic rat corpus cavernosum were similar to that of age-matched controls. These data demonstrated that the relaxant responses to cromakalim were altered in diabetic cavernosal strips in a time dependent manner, suggesting that the period of diabetes mellitus may play a key role in the K(ATP) channels function in rat corpus cavernosum.
本研究旨在探讨1周、2周、4周、6周和8周链脲佐菌素诱导的糖尿病大鼠海绵体条对ATP敏感性钾（K(ATP)）通道开放剂克罗卡林的舒张反应。克罗卡林（1 nM - 0.1 mM）在去氧肾上腺素（7.5 microM）预收缩的离体大鼠海绵体条中产生浓度依赖性舒张。与年龄匹配的对照动物相比，2周糖尿病动物中观察到克罗卡林诱导的海绵体舒张显著增强，而6周和8周糖尿病动物对克罗卡林的舒张反应降低。然而，与相应年龄匹配的非糖尿病组相比，1周或4周大鼠海绵体条中克罗卡林诱导的舒张没有改变。用K(ATP)通道阻滞剂格列本脲（10 microM）预孵育可显著抑制非糖尿病和糖尿病大鼠海绵体中克罗卡林诱导的舒张，但电压依赖性钾（K(V)）通道拮抗剂4 - 氨基吡啶（1 mM）和钙激活钾（K(Ca)）通道拮抗剂蝎毒素（0.1 microM）对对照和糖尿病大鼠海绵体条中克罗卡林诱导的舒张均无显著影响。糖尿病大鼠海绵体对一氧化氮供体硝普钠（1 nM - 0.1 mM）的舒张反应与年龄匹配的对照相似。这些数据表明，糖尿病海绵体条对克罗卡林的舒张反应呈时间依赖性改变，提示糖尿病病程可能在大鼠海绵体K(ATP)通道功能中起关键作用。
