BIBL~ISSN~53-97,56 Acta Pharmaco!ogica simca中国药理学报 1997 Nov;18(6) '5
7丑啪g I..He ,Liu CG Effect of extrace]luIar calcium off (军事医学科学院毒物药物研究所.北京100850,中国) 幻
desensitization of nieotlmc receptors in cultured rat g~}lelic
neurons J Phil ToxL~o]1 ;10:8―11 关键词交感神经节;烟碱受体;毒扁豆碱;
8 HamiliOP-MmS A,Neher E,Sflwa~am B,sig帅 F/ 变构调 蘸 再 术一―一
hT ved ~aniques for high-reso]ution cm-~nt Hd 一'
酬 叩 目的:研究毒扁豆碱阻断交感节神经元烟碱受体
Pf1 Archl98l;391:85―100. 一… … …一…… .一 '一 一
9 Mo N.D吼NI,K AG Facilitation and iahibili0n of 的作用机理.方法:以培养的新生大鼠颈上交感
nicotinicwamrmssion by eserineinthe Ⅻc ganglia ofthe 节神经元为标本,使用全细胞膜片箝技术,观察
.
;24 O93―101. 毒扁豆碱对交感节烟碱受体选择性激动剂DMPP
Al j m甜 .IIs of廿Ie niaximc acety]choline武州 诱发电流的影响.结果:毒扁豆碱(5一∞ m01
TrendsNeumsci L993;16:181―6 L-1) 浓度依赖性方式抑制DMPP诱发电流,促
" ".: . ' ep ―,进诱发电流的衰减,其抑制作用没有电压依赖性,
l粥7:10:蜥一50 ./毒扁豆碱20O mI.L 不能激活烟碱受体.结
,0 一 f 论:与骨骼肌烟碱受体相比,交感神经元烟碱受
毒扁豆碱阻断大鼠交感节神经元烟碱乙酰胆碱 体表现出不同的药理学特性
.毒扁豆碱通过作用
.卫 于变构位点抑制交感神经元烟碱受体,不影响其
郑建垒,何湘平,扬爱珍,刘传缋 . 1 I I 开放的离子通道和激动剂结合位点.
AcreI~axnacologica Si~ca中国药理学报 ]997 Nov;18(6):5 L L一5 L4
Elevation of an endogenous inhibitor of nitric oxide synthase
in diabetic rat serum1
XIONGYah,LURong,LIYuan.Jian2,DENGHan-Wu
(Department ofPharraacology,Hunan Medical University,Changsha 410078,China)
KEY WORDS argin]ne;e] l叫
mdlitus; blood u00se; malondialdehyde
choline;tb0racIc aoita
AIM:To study the朗xl0g朗10Ils inhibitor of NO
Ⅱlhase , .dimc~l-arginine(DMA)in the
diabe廿c rat sE舯蚰. METHODS:In slre口t0 n.
induced diane rats.the 】m DMA level and
endothelitma-depondent vasorelaxation to acetytcholine
(ACh)we∞determined. RESULTS:The sE 】m
DMA concentration was ineleased in the diab c rats
comparedwith their ag~-matched eonlrols(5.4±1.0
坩0.7±0.3 umol L一 ,P0.05).
Vasodilator responses to ACh were markedly
attenuated in diabetic rings.Preincubation with L―
arginine 1 mnlol L一 mduced a肚enuaDed vasodilator
responsesin diabetic rings(Fig1).
\
C o
: 墨
0
正
Acetylcholine/一Ig tool.L―
AaI.A:Effect of hyperg]yom~∞vasodi]ator
r'哼p叽瞄to ACh-m diabetic rats(●)m1d match
control rats(0)cn=10).B:Effect ofL.卸 曲 1
mmol L一 on inhibidou of vasodilator~sponses to
AaI by hypergtyce~da in the absen4~(0)or
presence(●)of L 衄 曲 (n=5). 2±s.
bp'0.o5.cp'0.o1 match control珀_乜雎the
ringsmUreatedwith L a 吐njne.
DISCUSS10N
Ttle present study~~)nfirrns previous observations
that hyperglycemia attenuates endor.helium dependent
vasorelaxation to ACh,which is impmv~by
preincubafion ll1 L gl~ine.a precursor ofNoL .
and demonstratesforthefirsttimethatthe serumlevel
of endogenous DMA is raised i171 stmptozocin-induced
diabedc rats. Endogenous or exogenous inhibitors of
NO synthase attenuated endothelium-dependent
vasorelaxafion 一.and trea~.nt with L一舡画 ∞in
vivo or in vitro improved endotbelitma-dependem
vasorelaxation in diabetic or hyperc~lesterolemic
animals , .These results.together with previous
studies that eadothelium-dependent relaxation to A0l
in hylxa~holesterolemic vessels was attenuated.while
the serumlevel ofendogenousDMAwasincreas芒din
hypercholestemlecnic rabbits " . suggest that
endogenousDMA may be a conmbutor to aaenueted
endothelium―dependent vasorelaxation in diabetic rats.
The m.chanism for the iIlcrease of DMA in the
serum of diabetic rats is not clear.Several possible
m~harliSlllS have been considered. Ftrst,blood
c~ntrafions ofDMA increased in Dati with
chronic renalfailure.whichwas ascribedtol'~klction
in excretion of DMA J. Kidney danla~e was shown
in$~zocin.induced diabetic rats."Iherefore,the
possibility that[educ~on in excretion of DMA was
considered in diabetic rats.However.all K 翟se in
sertlinlevels ofDMAmay be duetothe stimulation of
DMA production n~lerthanthem血 衄in excretion
ofDMA in hypercholesterolemic rabbitsL .
Second,it is weⅡestablished that n ldl1ase
C(PKC)activation plays all important 1"ole in the
development of vascular disease in diabetesL .
Activation of眦can directly cruise changes in the
actions of vario~enzymesin additionto altering岫
expression at the e血level .Dimethylarginine
dimethylamin~ydrolase (DDAH) metabolizes
methytazgimnesto citmlline,andit has been$11ggP.,stgd
that decreased activity of DDAH leads to local
accumulation ofDMA andinhibitionofNo synthase.
effects that would be reversed by L.a"dnineL14J.
VitaminE preventedthe activation ofPKCinduced by
hyperglycemiat
. Our recelat smdy showed that
supplemem with vitamin E decreased DMA conterlt in
hypercholestemlemic rabbits .These血diI1gs allow
us to suppose that the increase of DMA may be
secondary to the inhibition of DDAH activity v/a the
H pathway.However,如Ill1既studies meas~ng
activ 0f DDAH and H need to be done to
establish this hypothesis for the relatiomhip betweeu
the level ofDMA and眦activation.
Third,we have recently shown that the se
ofDMAis relatedtothe elevation oflipid pe~xides,
because the increase of DMA is accompanied by an
514. BIBL~:ISSN~53-9756 Acta 邮T日硎.画 Sthica中国药理学报 1997Nov;18(6)
elevation of malondialdehyde(mA)1evel and
sup01ement with antioxidam vitamin E decreases lipid
pemxides concomitantly withthe reduction ofDMAin
the serum content in hyperlipidemic rabbitsL .
Oxygen free radicals and lipid peroxide pLay all
important role in the development of diabetic
complications such as athewsclerosis.In the present
studythe concentration ofDMAwasincreased with all
elevation ofmA content in diab~c rats.However.
the relationship betweenlipid peroxide and DMA1evel
in diabefic rat serulTl is a ixoblem for further
elucidation.
In stmlmary,this study demonstrated forthe first
time that the semm level of endogenous DMA was
increasedinthe streptozocin-induced diabeticmt.Tbe
presellt results also suggestthat eIld0geⅡ0usDMAmay
be a con~butor to attenuated end0山elium.dependent
vasorelaxmionin diabetic rats.
neA'vl~irLthe sathmuctals pl既us of 阱m diab~c赋ileum
~logy 1990;98:1427―36
9 Yagi K A simpleflt~ommic assayfor~xideirL blcod
plasma.BiochemMed1976:15:212―6
10 ParkKS,LeeHW.Hortg SY,Shin S,Kim S,PaikWK
Detenninafic~of r蛐l删amino∞ in hmmn serum by 一
perf~'nmceⅡ 耐aw0mswg,,ephy.
JOnnmaw~r1988;440:2'25―30
】】XiongY.Li Y丁,YuⅪ. GZ,LiNS
FJdoge∞usint'dbi~rsof nitric叽i syrups and1ipid pe~xidafion
irL hHJer]ipidcmic rab u.
Acta Phamm~l Sin】9%:17:149―52.
12 PorteD Jr.SchwartzMW Diabctcz~omplhaafiom:whyis gluco~
~otentially toxic Scic~e 1996;272:699―70.
13} 雌乱.1be mle of肿吼n nase C activation irL the
d d∞m∞t of va训ar disease in ab吣
CurtoDm End0c删Dhabe~s】9 ;3:285―90
14 MacAJfister RJ r larry H,K~ncto M,Ogawa T.Russell R『,
Hodson H, a/ gII 锄of nitric oxide sy~hesis by
碰n蚓l埘hrgillille dimmhyl-amino~olase.
Br J Phammcol19晰;119:1533―40.
15 KtmimkiM,FumioU,NawataH, .
Vit,~nha E no~nnalizes diacylglyceool-i:ootein kinase C adi on
1Ⅺ 8 Y,Li YJt HW.融 ∞of L-~inln*against Diaba~1996;45 Suppl 3:Sl17一Sl19
induced by in
.
U 瑁 盟血r va9 l丑r sn . ,
oxygenfreem:ik:~s-hajuredlabor am ealdothdlttm一 JI. f
Aoa m Sm 科; :119-23. 糖尿病大鼠血中内源性一氧化氮合酶抑制物增高
2 VaU~ce P.L涨A,CslvctA.Colli~J,Mooc~a S
cII曲I1 of蛆∞ 叫s mbiblto~of c oxide s~csis irL
d玳m r∞ false I~ncct I992;339:572―5.
3 YuⅪ.Ij YJ,)d0IIgY Incr~of蛐∞曲 i 0f
niⅡ oxide svⅡ山es Im of t岫~lestero]fed
Life SciI9舛:5,t:了53一B.
4 0 日MA-Gaua r GirerdⅪ,Colem~SM,DzauⅥ,
Cooke JP L-舡 1 e i 呷∞v 咖d0出e1iL1 depe t va∞ 蜘肌
bv咪b e .啪Id humam
J Cl lnve~1992:90:l248―53
5 Cooke|P-Singer AH.Tmo P,Zeta P.R0w虮RA.B丑 曲m
~匝Anaathn~ic tfffects of L-argmine in the hyper-
ehol~ci',d#/fit
J Chnlnve~1992;90:ll6B一72
6 Pittxr t№BA Amelioration by L―q_ml鼬of a
时sflmaional mglnine./ni~c oxide pathway iⅡdiab~c elldo~aelittm
JCardiovlL~Pharmaecl19%;25:397―403
7 IgA.Valemi P.Sachs R.Da5M, E.AtmU JR
『n略出口吼【of coltma~"v&scIl 丑r陀serve and A01一induced coronary
Ⅷ舯 锄'Ⅲdial:l~ic p蚵cIIts with鲫画og呷bicaIly rtofBlal
0咖a Ⅲ es and normalleft vellnSzalar systolicflm~on
Di曲cIcs 19鳃;42:10l7―25
8 At Bumstock G a婶s irL 咄and pclMJd~ic
垡 .璺一蓉 李元建z,邓汉武lz.}兽7/.L
(湖南医科大学药理教研室,长抄410078,中国)
关键词盔 ;实验性量垦 :血糖;丙二醛;
乙酰胆碱;胸主动脉一 b鬟临两巷 .]
目的:测定糖尿病大鼠血中内源性NO合酶抑制
物二甲基精氨酸(DMA)的含量.方法:在链佐星
诱发的糖尿病大鼠测定血清DMA的含量和乙酰
胆碱(ACh)诱导血管内皮依赖性舒张.结果:与
对照组相比,糖尿病大鼠DMA血清浓度显著增加
(5.4±1.0 w 0.7±0.3 urnol L一,P