TY - JOUR
T1 - Investigating the effects of the Rho-kinase enzyme inhibitors AS1892802 and fasudil hydrochloride on the contractions of isolated pregnant rat myometrium
AU - Ergul, Merve
AU - Turgut, Nergiz H.
AU - Sarac, Bülent
AU - Altun, Ahmet
AU - Yildirim, Şahin
AU - Bagcivan, Ihsan
N1 - Publisher Copyright:
© 2016 Elsevier Ireland Ltd. All rights reserved.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - 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 EC 50 (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 × 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.
AB - 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 EC 50 (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 × 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.
KW - AS1892802
KW - Fasudil hydrochloride
KW - Myometrium
KW - Rho-kinase inhibitor
KW - Tocolysis
UR - http://www.scopus.com/inward/record.url?scp=84965129386&partnerID=8YFLogxK
U2 - 10.1016/j.ejogrb.2016.04.031
DO - 10.1016/j.ejogrb.2016.04.031
M3 - Artículo
C2 - 27160814
AN - SCOPUS:84965129386
SN - 0301-2115
VL - 202
SP - 45
EP - 50
JO - European Journal of Obstetrics and Gynecology and Reproductive Biology
JF - European Journal of Obstetrics and Gynecology and Reproductive Biology
ER -