Investigating the effects of the Rho-kinase enzyme inhibitors AS1892802 and fasudil hydrochloride on the contractions of isolated pregnant rat myometrium
| Autor: | Bülent Saraç, Nergiz Hacer Turgut, Ihsan Bagcivan, Sahin Yildirim, Ahmet Altun, Merve Ergül |
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| Přispěvatelé: | [Ergul, Merve -- Turgut, Nergiz H.] Cumhuriyet Univ, Fac Pharm, Dept Pharmacol, PK 848, TR-58140 Sivas, Turkey -- [Sarac, Bulent -- Altun, Ahmet -- Yildirim, Sahin -- Bagcivan, Ihsan] Cumhuriyet Univ, Fac Med, Dept Pharmacol, TR-58140 Sivas, Turkey |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Pyridines Hydrochloride Tocolysis Rho-kinase inhibitor Uterine contraction Uterine Contraction 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pregnancy 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Internal medicine Animals Medicine Rats Wistar Protein Kinase Inhibitors rho-Associated Kinases biology business.industry Phenylurea Compounds Myometrium Fasudil Obstetrics and Gynecology Fasudil hydrochloride Smooth muscle contraction Actin cytoskeleton AS1892802 Rats Nitric oxide synthase 030104 developmental biology Endocrinology Reproductive Medicine chemistry Rho kinase inhibitor biology.protein Female medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | European Journal of Obstetrics & Gynecology and Reproductive Biology. 202:45-50 |
| ISSN: | 0301-2115 |
| DOI: | 10.1016/j.ejogrb.2016.04.031 |
| Popis: | WOS: 000379095300009 PubMed ID: 27160814 Objectives: Rho-kinases (ROCKs), are one of the dynamic structures of the actin cytoskeleton and they mediate different biological processes, including regulation of calcium sensitivity of smooth muscle contraction. The activation of Rho A/ROCK system is thought to be effective on the termination time of the pregnancy process. The aim of this study, was to investigate in vitro effects of the ROCK enzyme inhibitors, clinically available fasudil hydrochloride, and a new promising inhibitor AS1892802, on the contractions of isolated pregnant rat myometrium. Study design: Term pregnant Wistar albino rats (n = 12), weighing 200-220 g, were used in this study. Myometrial tissues obtained from rats were dissected into four full-thickness longitudinal muscle strips and then myometrial tension was recorded isometrically. The inhibitory effects of cumulative concentrations of AS1892802 and of fasudil hydrochloride in the presence and absence of ODQ (guanylate cyclase inhibitor), L-NAME (nitric oxide synthase inhibitor) and L-NNA (endothelial nitric oxide synthase inhibitor) on oxytocin-induced myometrial contractions were measured, and values for -log10 EC50 (pD(2)) and mean maximal inhibition (E-max) were compared. Results: Both ROCK inhibitors, AS1892802 and fasudil hydrochloride starting from the concentrations of 10(-6) M reached statistical significance on contraction amplitude and frequency of myometrial strips (p < 0.05). The inhibition of the amplitude and frequency of myometrial contractions was antagonized with ODQ (10(-5) M; only amplitude), L-NAME (3 x 10(-5) M) and L-NNA (10(-5) M) (p < 0.05). Conclusion: These results suggest that fasudil hydrochloride and AS1892802 may contribute to the development of new tocolytic drugs. We conclude that AS1892802 and fasudil hydrochloride perform this inhibitory effect partially through ROCK inhibition and the NO/cGMP pathway. (C) 2016 Elsevier Ireland Ltd. All rights reserved. Cumhuriyet University Scientific Research Project (CUBAP, Sivas, Turkey) [T-587] This study was supported by Cumhuriyet University Scientific Research Project T-587 (CUBAP, Sivas, Turkey). |
| Databáze: | OpenAIRE |
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