title: The effect of sub-chronic systemic ethanol treatment on corpus cavernosal smooth muscle contraction: the contribution of RhoA/Rho-kinase.
abstract: 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.
authors.affiliation: Department of Pharmacology, Medical Faculty, Çukurova University, Adana, Turkey.
authors.forename: Eda Karabal
authors.initials: EK
authors.lastname: Kumcu
authors.affiliation: Department of Pharmacology, Pharmacy Faculty, Çukurova University, Adana, Turkey.
authors.forename: Fatma
authors.initials: F
authors.lastname: Aydinoglu
authors.affiliation: Department of Plant and Animal Production, Mudurnu Süreyya Astarci Vocational School, Abant Izzet Baysal University, Bolu, Turkey.
authors.forename: Erhan
authors.initials: E
authors.lastname: Astarci
authors.affiliation: Department of Pharmacology, Medical Faculty, Çukurova University, Adana, Turkey. ogulener@gmail.com.
authors.forename: Nuran
authors.initials: N
authors.lastname: Ogulener
mesh_terms: D000818:Animals; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010413:Penis / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
chemical_list: D010656:Phenylephrine; D000431:Ethanol; D011189:Potassium Chloride; C515854:Rock1 protein, mouse; C515855:Rock2 protein, mouse; D054460:rho-Associated Kinases; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
keywords: Ethanol; KCl; Mouse corpus cavernosum; Phenylephrine; RhoA/Rho-kinase