Improve of erectile function in diabetic rats through regulation of RhoA/ROCK signaling pathway by Bkca

Abstract:

Objective：To investigate the effect of big conductance Ca2+-activated K+ channel（BKca）on RhoA/ROCK signaling pathway of diabetes mellitus-induced erectile dysfunction（DMED） rats. Methods：Rats were divided into control group（n=8），DMED group（n=8） and NS1619 group（treatment group，n=7）. The NS1619 group was treated with BKca specific opener（NS1619） for two weeks. Rats underwent cavernous nerve stimulation to determine the value of intracavernous pressure（ICP）/mean arterial pressure（MAP） and the number of erection was recorded. Corpus cavernosum smooth muscle was isolated for detection of contractile force. Western blot and real-time PCR were used to detect the expression of RhoA，ROCK1，ROCK2，which determined the differences of RhoA/ROCK signaling pathway and phosphorylation of myosin light chain phosphatase（MLCP）. Results：DMED rat models were successfully estab－lished. While erectile function and compliance of smooth muscle was decreased in rats with DMED，administration of NS1619 im－proved erectile responses（P=0.025，0.024） and compliance（P=0.031，0.024）. Treatment significantly decreased the expression of RhoA，ROCK2 and MYPT-1（P=0.029，0.003，0.002），but not ROCK1（P=0.533）. Compared with those in control group the NS1619 group have a higher expression levels of those protein（P=0.018，0.040，0.003）. Conclusion：Up-regulation of the RhoA/ROCK sig－naling pathway is harmful to erectile function. Activation of BKca can improve erectile function by down-regulation the level of RhoA/ROCK and phosphorylation of MLCP.