Kumcu Eda Karabal, Aydinoglu Fatma, Astarci Erhan, Ogulener Nuran
Department of Pharmacology, Medical Faculty, Çukurova University, Adana, Turkey.
Department of Pharmacology, Pharmacy Faculty, Çukurova University, Adana, Turkey.
Naunyn Schmiedebergs Arch Pharmacol. 2016 Mar;389(3):249-58. doi: 10.1007/s00210-015-1204-4. Epub 2016 Jan 4.
The aim of this study was to evaluate whether the sub-chronic systemic ethanol exposure has direct effect on cavernosal smooth muscle contractions induced by KCl (depolarizing) and phenylephrine (α1-receptor agonist), and the possible involvement of RhoA/Rho-kinase pathway. Sub-chronic systemic ethanol was applied to mice with inhalation route for 14 days. The blood levels in ethanol-treated mice averaged 121.2 ± 9.1 mg/dl. KCl (80 mM) and phenylephrine (10 nM-100 μM) induced sustained contractions in corpus corporal strips from sham-treated mice. Sub-chronic ethanol treatment reduced the contractions to KCl. However, phenylephrine-induced contractions were not affected by ethanol treatment. Rho-kinase inhibitor fasudil (50 μM) and Y-27632 (50 μM) inhibited contractions to KCl and phenylephrine in sham-treated mice. Ethanol treatment increased the inhibitory effect of Rho-kinase inhibitors on contractions to phenylephrine. The relaxations induced by fasudil (100 μM) and Y-27632 (500 μM) did not change in ethanol treatment group. In ethanol-treated group, the expression of RhoA decreased compared to sham-treated group. Also, ROCK1 expression was reduced by ethanol but not statically significant to sham-treated group; however, the expression of ROCK2 increased in ethanol group. From these findings, it seems that phenylephrine and KCl-induced contractions depends on RhoA/Rho-kinase-mediated Ca(2+) sensitization. Also, these results suggest that the ethanol treatment decreased the expression of RhoA, and the inhibitory effect of ethanol on KCl-induced contractions may be due to, at least in part, the inhibition of a RhoA/Rho-kinase in mouse corpus cavernosum.
本研究的目的是评估亚慢性全身乙醇暴露是否对氯化钾（去极化剂）和去氧肾上腺素（α1受体激动剂）诱导的海绵体平滑肌收缩有直接影响，以及RhoA/ Rho激酶途径是否可能参与其中。通过吸入途径对小鼠进行14天的亚慢性全身乙醇处理。乙醇处理小鼠的血液乙醇水平平均为121.2±9.1mg/dl。氯化钾（80mM）和去氧肾上腺素（10nM - 100μM）可诱导假处理小鼠海绵体条带产生持续收缩。亚慢性乙醇处理可减弱对氯化钾的收缩反应。然而，去氧肾上腺素诱导的收缩不受乙醇处理的影响。Rho激酶抑制剂法舒地尔（50μM）和Y - 27632（50μM）可抑制假处理小鼠对氯化钾和去氧肾上腺素的收缩反应。乙醇处理增强了Rho激酶抑制剂对去氧肾上腺素收缩反应的抑制作用。法舒地尔（100μM）和Y - 27632（500μM）诱导的舒张在乙醇处理组中未发生变化。在乙醇处理组中，与假处理组相比，RhoA的表达降低。此外，乙醇使ROCK1的表达降低，但与假处理组相比无统计学意义；然而，乙醇组中ROCK2的表达增加。从这些发现来看，去氧肾上腺素和氯化钾诱导的收缩似乎依赖于RhoA/Rho激酶介导的Ca(2+)致敏。此外，这些结果表明，乙醇处理降低了RhoA的表达，乙醇对氯化钾诱导收缩的抑制作用可能至少部分归因于对小鼠海绵体中RhoA/Rho激酶的抑制。
