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

Abstract

To investigate the mechanism of ATP-sensitive potassium channel (K(ATP)) on nitride oxide (NO) regulating contractile activity of isolated lymphatics from hemorrhagic shock (HS) rats. 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 combined or respectively with K(ATP) inhibitor glibenclamide (Gli), opener of K(ATP) pinacidil (Pin), NO donor L-arginine (L-Arg), protein kinase A (PKA) inhibitor H-89, PKA donor 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-1-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. 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. K(ATP) involved in NO modulating pumping function of isolated lymphatics of HS rats, and the effect may be relative to the signal pathway of NO-cAMP-PKA and NO-cGMP-PKG.