Vasorelaxant effect of novel Rho-kinase inhibitors on isolated thoracic aorta rings and underlying mechanisms
10.3969/j.issn.1001-1978.2016.10.015
- VernacularTitle:新结构Rho激酶抑制剂对离体胸主动脉血管环舒张作用及机制研究
- Author:
Tianyi YUAN
;
Subo WANG
;
Huifang ZHANG
;
Yucai CHEN
;
Xiaozhen JIAO
;
Ping XIE
;
Lianhua FANG
;
Guanhua DU
- Publication Type:Journal Article
- Keywords:
Rho-kinase inhibitors;
isolated aorta rings;
vasodilation;
endothelium;
K+ channels;
Ca2+channels
- From:
Chinese Pharmacological Bulletin
2016;32(10):1404-1410
- CountryChina
- Language:Chinese
-
Abstract:
Aim To evaluate the vasorelaxant effect of two new chemical entities, J35242 and J35243, on iso-lated rat thoracic aorta rings as Rho-kinase inhibitors, and further to explore the underlying mechanisms of these two compounds. Methods Isolated rat thoracic aorta rings pre-contracted by KCl or norepinephrine ( NE) were used to evaluate the vasodilatory effect of J35242 and J35243 . Through the interventions of sev-eral tool drugs, the mechanisms of compounds concern-ing endothelium, K+ channels and Ca2+ were studied. Results J35242 and J35243 showed potent relaxant effect on both KCl and NE pre-contracted vessels, and exhibited partial endothelium dependency. L-NAME and Methylene Blue( MB) could influence the relaxant effect of these compounds. Meanwhile, the compounds could inhibit intracellular Ca2+ release and extracellu-lar Ca2+ influx, which indicated that the compounds might block the calcium channels to relax the vessels. In addition, the two compounds probably did not dilate the aorta rings through opening potassium channels. Conclusions J35242 and J35243 have vasorelaxant effects on vessels in vitro and the potency of J35242 is stronger than that of J35243 . The underlying mecha-nisms might be endothelium-dependent. Also the com-pounds might block Ca2+ channels, lowering intracel-lular Ca2+ concentration to relax the vessels.
