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ATP-sensitive potassium channel involved in modulation of nitride oxide regulating contractile activity of isolated lymphatics from hemorrhagic shock rats

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Author:
No author available
Journal Title:
Chinese Critical Care Medicine
Issue:
8
DOI:
10.3760/cma.j.issn.1003-0603.2012.08.004
Key Word:
失血性休克;离体实验;淋巴管;收缩性;一氧化氮;ATP敏感性钾通道;Hemorrhagic shock;In vitro;Lymphatics;Contractility;Nitric oxide;ATP-sensitive potassium channel

Abstract: Objective To investigate the mechanism of ATP-sensitive potassium channel (KATP) on nitride oxide (NO ) regulating contractile activity of isolated lymphatics from hemorrhagic shock ( HS ) rats.Methods Eighty four Wistar rats were randomly divided into control group (n=6),HS 0.5-hour group (n=36),HS 2-hour group (n=42).A segment of thoracic duct of rats was adopted for isolated lymphatics after HS,then the HS 0.5-hour and 2-hour lymphatics were incubated combinedly or respectively with KATP inhibitor glibenclaimde ( Gli ),opener of KATP pinacidil (Pin),NO doner L-arginine (L-Arg),protein kinase A (PKA) inhibitor H-89,PKA doner 8-bromine-cyclic adenosine monophosphate (8-Br-cAMP),nitricoxide synthase ( NOS ) inhibitor N-nitro-L-arginine methyl ester (L-NAME),soluble guanylyl cyclase (sGC) inhibitor 1 h-[1,2,4]-oxadiazole-[4,3-a]-quinoxalin-l-one (ODQ),protein kinase G (PKG) inhibitor KT-5823 (named as HS 0.5 h,HS 0.5 h + L-Arg,HS 0.5 h + L-Arg + H-89,HS 0.5 h + L-Arg + Gli,HS 0.5 h + 8-Br-cAMP,HS 0.5 h + 8-Br-cAMP + Gli and HS 2 h,HS 2 h + L-NAME,HS 2 h + L-NAME + Pin,HS 2 h + ODQ,HS 2 h + ODQ + Pin,HS 2 h + KT-5823,HS 2 h +KT-5823 + Pin,n=6).By lymphatic perfusion in vitro,contractile frequency (CF) was recorded,and contractile amplitude (CA),tonic index (TI) and fractional pump flow (FPF) were calculated.Results The results suggested that the CF,TI,FPF of HS 0.5-hour lymphatics were significantly increased compared with control group,and the CF,TI,FPF decreased significantly when incubated with L-Arg.H-89 could deteriorate the decreased effect of L-Arg on CF and FPF,and Gli could deteriorate the decreased effect of L-Arg on FPF.When the HS 0.5-hour lymphatics incubated with 8-Br-cAMP,the CF and FPF were all decreased significantly,and when the HS 0.5-hour lymphatics incubated with 8-Br-cAMP and Gli,the CF was significantly higher than HS 0.5 h + 8-Br-cAMP group,and the TI and FPF decreased significantly compared with HS 0.5-hour group.The CF,FPF,TI of HS 2-hour lymphatics were significantly decreased compared with control group.L-NAME could increase the CF,TI,FPF; ODQ could increase the CF,TI; KT-5823 could increase the CF and FPF; when incubated with Pin respectively,the CF and FPF when incubated with L-NAME were decreased,the CF,TI and FPF when incubated with ODQ were decreased,in addition,the CA was recovered as level of control group,the CF and FPF when incubated with KT-5823 were decreased.Conclusion KATP involved in NO modulating pumping function of isolated lymphatics of HS rats,and the effect may berelative to the signal pathway of NO-cAMP-PKA and NO-cGMP-PKG.

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