Glabridin Relaxes Vascular Smooth Muscles by Activating BK_(Ca) Channels and Inhibiting Phosphodiesterase in Human Saphenous Vein  

作　　者：Cengiz Giüven Ali Parlar 

机构地区：[1]Department of Cardiovascular Surgery,Faculty of Medicine,University of Adiyaman,Adiyaman 02040,Turkey [2]Department of Pharmacology,Faculty of Medicine,University of Adiyaman,Adiyaman 02040,Turkey

出　　处：《Current Medical Science》2021年第2期381-389,共9页当代医学科学（英文）

摘　　要：The aim of the current study was to investigate the pharmacological activity of glabridinon the isolated human saphenous vein (SV) and explore the underlying mechanisms. Samples of patients' SVs were removed during bypass surgery, and 4-mm lengths of the vessels were placedin Krebs solution at ±4℃ and hung in an isolated organ bath to assess their contraction/relaxationresponses. The contraction/relaxation responses were recorded to observe if the cyclic guanosinemonophosphate (cGMP)/protein kinase G (PKG) pathway mediates the relaxant effect of glabridinafter treatment with blockers like ODQ (a guanylate cyclase inhibitor), KT5823 (a PKG inhibitor),isobutylmethylxanthine [IBMX, a phosphodiesterase (PDE) inhibitor], and cantharidin [Cant,a myosin light-chain phosphatase (MLCP) inhibitor]. Moreover, nitric oxide (NO), cGMP, andPKG levels in SV tissues were determined by ELISA after incubation with glabridin, N(o)-nitro-L-arginine methyl ester (L-Name, a NO synthetase inhibitor), phenylephrine (PE), ODQ, IBMX,and KT5823. The results showed that glabridin relaxed the vascular smooth muscle of humanSV pretreated with PE in a dose-dependent manner, which was independent of the endothelium.The vasorelaxant effect of glabridin was only inhibited by iberiotoxin (IbTX), Cant, and KT5823.Glabridin increased cGMP and PKG levels in SV homogenates, whereas it did not alter the NOlevel. The enhancing efects of cGMP and PKG levels by glabridin were abolished by ODQ andKT5823. In conclusion, glabridin has a vasorelaxant effect, which is associated with the activationof BKc. channels and inhibition of PDE.

关 键 词：GLABRIDIN BKCa channels human saphenous vein(SV)grafts cyclic guanosine monophosphate(cGMP) protein kinase G(PKG) 

分 类 号：R73[医药卫生—肿瘤]