IAOe?IIAEUeIA AEAAeAI?ss IAOE OE?A?IE

?INOEOOO O?C?IEIA?? ?i. I.I. AIAIIIEUeOess

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Aiea?i Aeaien A?eoi?iae/

OAeE
612.2:612.821:616.24

AeINE?AeAEAIIss IAAeOEss?IEO IAOAI?CI?A O*ANO? IENEAeO ACIOO OA

?AOeAIOI??A N-IAOEE-D-ANIA?OAOO A ?AAOEssOe?? AeEOAEUeIIAI

?EOIIAAIACO O IIAIIA?IAeAEAIEO UO?ssO

03.00.13 — O?c?ieia?y ethaeeie ? oaa?ei

Aaoi?aoa?ao aeena?oaoe?? ia caeiaoooy iaoeiaiai nooiaiy

eaiaeeaeaoa a?ieia?/ieo iaoe

Eeaa — 1999

Aeena?oaoe??th ? ?oeiien

?iaioo aeeiiaii o a?aeae?e? ii aea/aiith a?iiene/ieo noai?a

?inoeoooo o?c?ieia?? ?i. I.I. Aiaiiieueoey IAI Oe?a?ie

Iaoeiaee ea??aiee: aeieoi? iaaee/ieo iaoe, i?ioani?

NA?AAeAIEI Ieoaeei Ieoaeeiae/

?inoeooo o?c?ieia?? ?i. I.I. Aiaiiieueoey IAI Oe?a?ie

caa?aeoaa/ a?aeae?eo ii aea/aiith a?iiene/ieo noai?a

Io?oe?ei? iiiiaioe: aeieoi? a?ieia?/ieo iaoe OAIIAAE Ethaeieea
Ieeiea?aia

?inoeooo o?c?ieia?? ?i. I.I. Aiaiiieueoey IAI Oe?a?ie

i?ia?aeiee iaoeiaee ni?a?ia?oiee a?aeae?eo

o?c?ieia?? e?iaiia?ao

aeieoi? iaaee/ieo iaoe NIEIAEIA Aiaoie?e ?aaiiae/

?inoeooo oa?iaeieia?? oa oieneeieia?? AII Oe?a?ie

aieiaiee iaoeiaee ni?a?ia?oiee a?aeae?eo

aenia?eiaioaeueii? oa?ai??

I?ia?aeia onoaiiaa: eaoaae?a o?c?ieia?? ethaeeie oa oaa?ei Ee?anueeiai

oi?aa?neoaoo ?iai? Oa?ana Oaa/aiea

Caoeno a?aeaoaeaoueny «_27_» «_ea?oiy_ » 1999 ?. i «_14__» aiaeei?

ia can?aeaii? niaoe?ae?ciaaii? a/aii? ?aaee Ae 26.198.01 i?e ?inoeooo?

o?c?ieia?? ?i. I.I. Aiaiiieueoey IAI Oe?a?ie ca aae?anith: 252024

Ee?a, aoe. Aiaiiieueoey, 4.

C aeena?oaoe??th iiaeia iciaeiieoeny o a?ae?ioaoe? ?inoeoooo o?c?ieia??

?i. I.I. Aiaiiieueoey

Aaoi?aoa?ao ?ic?neaiee «24» «_ethoiai» 1999 ?.

A/aiee nae?aoa? niaoe?ae?ciaaii? a/aii? ?aaee

aeieoi? a?ieia?/ieo iaoe C.I. Ni?ie?ia-Ia??ia

CAAAEUeIA OA?AEOA?ENOEEA ?IAIOE

Aeooaeuei?noue oaie. Iaiao?aei?noue aeine?aeaeaiiy oeaio?aeueii?
?aaoeyoe?? aeeoaeueiiai ?eoiiaaiaco o iiaiia?iaeaeaieo nnaaoe?a
iia’ycaia iiiaae ona c oei, ui a no?oeoo?? i?e/ei nia?oiino? ae?oae a
?aiiueiio iaiiaoaeueiiio ia?eiae? aeeoaeuei? ?iceaaee caeiathoue
i?ia?aeia i?noea. E??i oiai, a aeooa?nuee?e oa iaiiaoieia?/i?e
i?aeoeoe? aeei?enoiaothoueny oa?iaeieia?/i? i?aia?aoe, ye? iiaeooue
aooe aeiii?aie ieneaeo acioo (NO) ? aeieaoi?aie ?aoeaioi??a
N-iaoee-D-ania?oaoo (NMDA) (Ia?eiaa, Oaaaeia, 1993). A?aeiii, ui NO o
ia?aia?e nenoai? aeeiio? ooieoe?th ?ao?ia?aaeiiai ianaiaeaea?a,
iiaeoeyoi?a ye caoaeaeoth/i?, oae ? aaeuei?aii? neiaioe/ii?
ia?aaea/? (Dawson & Snyder, 1994; Wu & Dun, 1996), iieacaii eiai
ni?iiiaei?noue aei aeieoaaiiy iioaioe?aecaeaaeieo eaeueoe??aeo eaiae?a
iae?ii?a (Nieiaeiaa, Einothe, 1998). Iiaeeeaei oeyoii noeioeyoe??
aeoeaiino? oa?iaioo, ui a?ae-iia?aea? ca a?ineioac NO (NO-neioace), ?
ca?eueoaiiy aioo??oiueiee?oeiii? eiioeaio?aoe?? ?ii?a eaeueoe?th
aiane?aeie aeoeaaoe?? NMDA-?aoeaioi??a (Dawson & Snyder, 1994). Ia
oaia??oi?e /an o e?oa?aoo?? a?aenooi? aeai? i?i oeaio?aeueiee aieea NO
ia aeeoaeueiee ?eoi o iiaiia?iaeaeaieo oaa?ei, ye o ii?i?, oae ? ca
oiia a?iien??. Iaeiei ?c caaaeueiiaeciaieo iaoiae?a eieae?caoe??
iae?ii?a, ye? i?noyoue NO-neioaco, ? a?noio?i?/ia ?aeaioeo?eaoe?y
ia?ea?iiai oa?iaioo i?eioeiai?ae aaeai?i aeeioeeaioeae oinoao
(NADPH)-ae?aoi?ace (Dawson et al., 1991; Vincent & Kimura, 1992).
NADPH-ae?aoi?aci?aaeoeai? oa NO-neioaci?ioii?aaeoeai? iae?iie
eieae?ciaai? o aei?ineeo oaa?ei o iaaeoey?ieo no?oeoo?ao, i?e/aoieo aei
aaia?aoe?? aeeoaeueiiai ?eoio (Vincent & Kimura, 1992; Dun et
al.,1994). Aiaeia?/i? ?iaioe, ye? aoee a i?iaaaeai? ia iiaiia?iaeaeaieo
oaa?eiao, iaa?aeii?. ?ieue NMDA-?aoeaioi??a o ?aaoeyoe?? aeeoaeueiiai
?eoio o iiaiia?iaeaeaieo oaa?ei ia iaaeoey?iiio ??ai? caeeoa?oueny ia
inoaoi/ii c’yniaaiith. A ae-nia?eiaioao ia c??cao aeiaaanoiai iiceo
iiaiia?iaeaeaieo uo?yo io?eiai? aeai? i?i oa, ui NMDA-?aoeaioi?e ia
aa?ooue o/ano? a aeeoaeueiiio ?eoiiaaiac? (Funk et al., 1993).
Iaiao?aeii i?aee?aneeoe, ui oe? aeine?aeaeaiiy i?iaiaeeeeny a
?ic/ei? c i?aeaeuaiith ao?e/? eiioeaio?aoe??th ?ii?a eae?th,ui iiaea
i?ecaiaeeoe aei iioaioe?ae- aai eaeueoe?ecaeaaeii? aeanaineoecaoe??
NMDA-?aoeaioi??a (McBain & Mayer, 1994). ?acii c oei a?aeiii, ui
aie?eaoe?y aeciaaiiiai NMDA i?ecaiaeeoue aei noeioeyoe?? aeeoaeueiiai
?eoio, yeee aaia?o?oueny iaaeoeini?iaeueieie i?aia?aoaie
iiaiia?iaeaeaieo uo?yo (Greer et al., 1991; Kashiwagi et al., 1993).
I?ioe??//y ?nioth/eo aeaieo na?ae/aoue i?i iaiao?aei?noue i?iaeiaaeaiiy
aeine?aeaeaiue o aeaiiio iai?yieo. A?aeiii, ui ca a?iiene/ieo oiia
a?aeaoaa?oueny ca?eueoaiiy aea?eueiaiiy aeooaiaoo, ui iiaea i?ecaiaeeoe
aei aeoeaaoe?? NMDA-?aoeaioi??a (Mitiani at al., 1991; Johnston, 1997).
O/anoue NMDA-?aoeaioi??a o oeaio?aeuei?e ?aaoeyoe?? aeeoaeueiiai
?eoio o iiaiia?iaeaeaieo i?e a?iien?? i?e oeueiio ia ciaeoei
aeinoaoiueiai a?aeia?aaeaiiy a e?oa?aoo?ieo aeaea?aeao. Aeciaii, ui
a?aeoeeaiiy eiioeaio?aoe?? ?ii?a aiaeith aeey iaaeoey?ii?
oaii/ooeeaino? aeeoaiiy ? a?eueo neeueiei iiae?acieeii, i?ae a?aeoeeaiiy
aaciaiai neeaaeo (Eaeueiainii, 1997). Ca iiaeyaeii ?yaeo aeine?aeiee?a
(Cohen, 1979; Arita et al., 1988), oeaio?aeuei? oaii?aoeaioi?e
aaio?aeueii? iiaa?oi? aeiaaanoiai iiceo iaaeathoue caoaeaeoth/iai
oii?/iiai aieeao ia ?ini??aoi?i? iae?iie ?eoiiaaia?oth/i? ia?aae?.
I?eionea?oueny, ui NMDA-?aoeaioi?e iiaeooue a?aoe o/anoue o
caoaeaeo/?e neiaioe/i?e ia?aaea/? ia oeyoao, ye? a?aeiia?aeathoue ca
iiaeoeyoe?th caoaeeeaino? ?eoiiaaia?oth/eo iae-?ii?a (Funk et al.,
1993). Aea cia/aiiy ?aoeaioi??a aeaiiai oeio oa aiaeiaaiiiai ieneaeo
acioo a iaaeoey?i?e oaii/ooeeaino? aeeoaiiy ia aea/aii.

Iaoa aeine?aeaeaiiy iieyaaea o aecia/aii? ?ie? NO oa
NMDA-?aoeaioi??a caoaeaeoth/eo ai?iieeneio o ?aaoeyoe?? aeeoaeueiiai
?eoio iiaiia?iaeaeaieo uo?yo ia iaaeoey?iiio ??ai?.

Aieiai? caaea/?:

1. Aeine?aeeoe NADPH-ae?aoi?acio ?aaeoeai?noue iae?ii?a
iaaeoey?ieo no?oeoo?, i?e/aoieo aei aeeoaeueiiai ?eoiiaaiaco, o
iiaiia?iaeaeaieo uo?yo.

2. Aea/eoe aieea NO oa aeieoaaiiy NMDA-?aoeaioi??a ia aeaeo?e/io
aeoeai?noue o ae?ao?aaiaeueiiio ia?a? /anoeiai ecieueiaaieo
iaaeoeini?iaeueiuo i?aia?ao?a iiaiia?iaeaeaieo uo?yo (*?INI).

3. Aecia/eoe ?ieue NO o ci?i? aeaeo?e/ii? aeoeaiino? o
ae?ao?aaiaeueiiio ia?a? *?INI i?ae /an aieeao NMDA.

4. Aeine?aeeoe aieea NO oa aeieoaaiiy NMDA-?aoeaioi??a ia
aeaeo?e/io aeoeai?noue o ae?ao?aaiaeueiiio ia?a? *?INI i?e
a?iien?? oa i?e cieaeaii? ?I ciai?oiueiee?oeiii? ??aeeie.

Iaoeiaa iiaecia iaea?aeaieo ?acoeueoao?a. Aia?oa aeine?aeaeaii
?iciiae?eaiiy iae?ii?a, ye? i?noyoue NADPH-ae?aoi?aco (a yeino? ia?ea?o
NO-neioace), oa ?o na?aaeith u?euei?noue a yae?ao aaio?aeueii? ?
aei?naeueii? ?ani??aoi?ieo a?oi iae?ii?a (A?A e Ae?A) aeiaaanoiai iiceo
iiaiia?iaeaeaieo uo?yo. Iieacaii i?enooi?noue i?/aieo ee?oei a yae?ao
A?A oa Ae?A, ?o iiioeyoe?th c iaea?eueoith u?euei?noth aeyaeaii a
?ino?aeuei?e /anoei? A?A – a iaeano? eaoa?aeueiiai ia?aa?aaioiee?oeiiiai
?aoeeoey?iiai yae?a. Aia?oa i?iaeaiiino?iaaii o/anoue NO a ?aaoeyoe??
aeeoaeueiiai ?eoio, yeee aaia?o?oueny *?INI iiaiia?iaeaeaieo uo?yo,
aeine?aeaeaii aeaye? iaoai?cie oe??? o/ano?. Aia?oa iieacaii ?ieue
aiaeiaaiiiai NI a oii?/iiio oi?iiciiio eiio?ie? aeeoaeueiiai ?eoio,
yeee cae?enith?oueny ?ino?aeueiith /anoeiith aaio?ieaoa?aeueiiai
a?aeae?eo aeiaaanoiai iiceo (AEAAeI) iiaiia?iaeaeaieo uo

?yo, o ii?i? ? ca oiia a?iiene/iiai oanoo. I?aeoaa?aeaeaii o/anoue
aiaeiaaiiiai NO a iiina?aaeeoaaii? aieeao aeoeaaoe?? NMDA-?aoeaioi??a
ia aeeoaeueiee ?eoi *?INI. Aia?oa aeine?aeaeaii ?ieue aiaeiaaiiiai NO a
iaaeoey?i?e oaii/ooeeaino? aeeoaiiy; iieacaii, ui oeae iae?iiiaeoeyoi?
iiina?aaeeiao? aeoeaaoe?th aeeoaeueiiai ?eoio *?INI i?e cieaeaii? ?I
noia?oocoth/iai ?ic/eio. Aia?oa aeine?aeaeaii aieea aeciaaiieo aeiii??a
NO ia aeeoaeueiee ?eoi *?INI. Iieacaii ca?eueoaiiy o?eaaeino?,
aiie?ooaee oa ?ioaa?aeueii? ?ioaineaiino? ?ini??aoi?ieo ?ic?yae?a (??)
c iaeii/aniei ciaioaiiyi ?o /anoioe i?e aie?eaoe?? aeiii??a NO.
I?iaeaiiino?iaaii ni?iiiaei?noue i?o?ii?oneaeo iao??th aei aeieoaaiiy
NMDA-?aoeaioi??a, ui aa?ooue o/anoue a ?aaoeyoe?? aeeoaeueiiai ?eoio
*?INI. Ca oiia a?iiene/iiai oanoo iiia?aaeiy aie?eaoe?y i?o?ii?oneaeo
iao??th i?ecaiaeeea aei a?eueo ae?aaeaiiai ca?eueoaiiy ?ioaa?aeueii?
?ioaineaiino? ?? ? iaioiai a?aeiiniiai i?eai?/aiiy ?o /anoioe, ui ?
i?aeoaa?aeaeaiiyi ?acoeueoao?a aenia?eiaio?a ?ioeo aeine?aeiee?a,
i?iaaaeaieo in vivo ia aei?ineeo oaa?eiao. O oeae aea /an aie?eaoe?y
i?o?ii?oneaeo iao??th i?e ianooiiiio aieea? ?ic/eio c? cieaeaiei ?I
ciaiooaaea noeioeyoe?th /anoioe aeeoaeueiiai ?eoio *?INI. Iaea?aeai?
?acoeueoaoe ?icoe?ththoue ?nioth/? oyaeaiiy i?i o/anoue NMDA-?aoeaioi??a
o ?aaoeyoe?? aeeoaeueiiai ?eoio ia iaaeoey?iiio ??ai? o
iiaiia?iaeaeaieo oaa?ei. Aia?oa iieacaii ca?eueoaiiy o?eaaeino? ?? o
ae?ao?aaiaeueiiio ia?a? *?INI i?e aie?eaoe?? eaoai?io, ui iiaea
na?ae/eoe i?i o/anoue NMDA-?aoeaioi??a o ia?aeeth/aii? aaeeoo ia aeaeeo
ia iaaeoey?iiio ??ai? o iiaiia?iaeaeaieo uo?yo. Oeae iaoai?ci
caaacia/o?oueny no?oeoo?aie ?ino?aeueii? /anoeie AEAAeI. Aia?oa
iieacaii o/anoue NMDA-?aoeaioi??a o oac? ei?ioei/anii? noeioeyoe??
aeeoaeueiiai ?eoio *?INI ca oiia a?iiene/iiai oanoo, a oaeiae o
a?eueo o?eaaeiio i?ioean? aeoeaaoe?? /anoioe aeeoaeueiiai ?eoio i?e
cieaeaii? ciai?oiueiee?oeiiiai ?I.

Oai?aoe/ia oa i?aeoe/ia cia/aiiy ?iaioe. ?acoeueoaoe
aeine?aeaeaiiy iathoue iaaio oai?aoe/io oe?ii?noue, ine?eueee
aeicaieythoue noi?ioaaoe iia? oyaeaiiy i?i iaaeoey?i? iaoai?cie o/ano?
NO ? NMDA-?aoeaioi??a o ?aaoeyoe?? aeeoaeueiiai ?eoio o
iiaiia?iaeaeaieo oaa?ei a ii?i?, a oaeiae i?e a?iien?? oa cieaeaii?
ciai?oiueiee?oeiiiai ?I, ye? a?aeaoaathoueny i?ae /an aaaaoueio
iaoieia?/ieo noai?a, o oiio /ene? ? aeeoaeueieo ?iceaae?a. I?aeoe/ia
cia/aiiy ?iaioe iieyaa? o aeaiiino?aoe?? iiaeeeaino? ci?ithaaoe
ia?aiao?e iaaeoey?iiai aeeoaeueiiai ?eoio iiaiia?iaeaeaieo oaa?ei oeyoii
oa?iaeieia?/iiai aieeao ia iaoai?cie eiai ?aaoeyoe?? ca o/anoth NO
oa NMDA-?aoeaioi??a.

Iniaenoee aianie caeiaoaa/a. Caeiaoaa/ai iniaenoi aeeiiaii anth
aenia?eiaioaeueio /anoeio, i?iaaaeaii aiae?c oa ocaaaeueiaiiy ??
?acoeueoao?a o ca’yceo c aeaieie e?oa?aoo?e. Caeiaoaa/ a?aa aeoeaio
o/anoue a iaaiai?aii? ?acoeueoao?a aenia?eiaio?a. Aia?oa caeiaoaa/ai
i?iaeaiiino?iaaii ?nioaaiiy o iiaiia?iaeaeaieo uo?yo ii?oieia?/iiai
aaceno o/ano? NO a ?aaoeyoe?? aeeoaeueiiai ?eoio, io?eiaii aeai? i?i
a??ia?aeiee aieea aiaeiaaiiiai NO oa aeciaaiieo eiai aeiii??a, a
oaeiae aeieoaaiiy NMDA-?aoeaioi??a ia ?ioaa?aeueio aeaeo?e/io
aeoeai?noue iaaeoey?iiai aeeoaeueiiai aaia?aoi?o. I?ia?aiia
caaacia/aiiy, ui ianeoaiao? aeaeo?io?c?ieia?/i? aenia?eiaioe,
?ic?iaeaia A.A. Oai?eii oa A.A. Ia?/aieii.

Ai?iaaoe?y aeena?oaoe??. Iniiai? iieiaeaiiy ?iaioe aeiiia?aeaeeny oa
iaaiai?thaaeeny ia XV C’?cae? Oe?a?inueeiai o?c?ieia?/iiai oiaa?enoaa
(Aeiiaoeuee, 1998), I?aeia?iaei?e eiioa?aioe?? «Hypoxia:
Destructive and Constructive Effect» (Ee?a, 1998), Anaoe?a?inuee?e
iaoeia?e eiioa?aioe??»I?iaeaie a?eiai? o?c?ieia??» (Eooeuee, 1998),
I?aeia?iaei?e eiioa?aioe?? «?ieue iiiiieneaea acioa a i?ioeannao
aeeciaaeayoaeueiinoe» (Ieine, 1998), I (onoaiia/?e) eiioa?aioe??
Oe?a?inueeiai oiaa?enoaa iae?iiaoe (Ee?a,1998),can?aeaiiyo a?aeae?eo
ii aea/aiith a?iiene/ieo noai?a ?inoeoooo o?c?ieia?? ?i. I.I.
Aiaiiieueoey IAI Oe?a?ie (1997,1998), can?aeaii? naeoi?o o?c?ieia??
a?noea?aeueieo nenoai ?inoeoooo o?c?ieia?? ?i. I.I. Aiaiiieueoey IAI
Oe?a?ie (1998).

Ioae?eaoe??. Ca ?acoeueoaoaie ?iaioe iioae?eiaaii /ioe?e noaoo? oa
oace i’yoe aeiiia?aeae.

No?oeoo?a oa ianya aeena?oaoe??. Aeena?oaoe?y neeaaea?oueny c?
anooio, iaeyaeo e?oa?aoo?e, iieno iaoiae?a aeine?aeaeaiiy, ?acoeueoao?a
aeine?aeaeaiiy, iaaiai?aiiy ?acoeueoao?a, aeniiae?a oa nieneo
aeei?enoaieo aeaea?ae ?c 177 iaeiaioaaiue. ?iaioo aeeeaaeaii ia 156
noi??ieao oa ?ethno?iaaii 22 ?enoieaie ? 5 oaaeeoeyie .

INIIAIEE CI?NO AeENA?OAOe??

Iaoa??aee oa iaoiaee aeine?aeaeaiue.

A?noio?i?/i? aeine?aeaeaiiy i?iaaaeai? ia 8 o?e-/ioe?eaeiaiaeo
uo?yoao e?i?? A?noa?. Aeyaeaiiy NADPH-ae?aoi?aci?aaeoeaieo (NADPH-ae)
no?oeoo? i?iaiaeeeiny ca aeiiiiiaith iiaeeo?eiaaiiai iaoiaeo
A?inaioa ? E?io?e (Vincent & Kimura, 1992; Petrovicky & Nemcova,
1995) ia o?iioaeueieo c??cao aeiaaanoiai iiceo oa ia?oeo o?ueio
naaiaio?a nieiiiai iiceo. I?ae aeeaieei ao??iei ia?eicii o oaa?ei
?ice?eaaee iicie, yeee i?ney 10-15 oa noia?ooc?? o?enaoi?ii (4-5%
ia?aoi?iaeueaeaa?aeo ia 0.1 I oinoaoiiio aooa??, pH 7.3) aeae?eyee ?
i?ioyaii 2 aiae i?iaiaeeee iinoo?enaoe?th i?e 4-50 N. I?ney 24 aiae
aeniiceoe?? a 15%-io ?ic/ei? naoa?ice o e??inoao? aeaioiaeyee c??ce 50
iei caaoiaoee. I?iaiaeeee a?noio?i?/io ?aaeoe?th o na?aaeiaeu? 0.1 I
oinoaoiiai aooa?o (pH 7.3), ui i?noeei 0.3% o?eoiio O-100, 0.5 ia/ie
aeaeeoiueiai oao?acie?oia, 1.0 ia/ie NADPH iao???ai? nie? oa 1.2 ia/ie
iaeaoo iao??th (an? ?aaeoeae ae?iaieoeoaa «Sigma,» NOA), i?e 37o N
i?ioyaii 40-60 oa. Aeine?aeaeaiiy c??c?a oa ?o i?e?ioioia?aooaaiiy
cae?enithaaee ca aeiiiiiaith na?oeiaiai i?e?ineiio («Carl Zeiss,
Jena», I?ia//eia). Eieae?caoe?th NADPH-ae-?aaeoeaieo ee?oei ia
noaiao o?iioaeueieo c??c?a i?iaiaeeee ca aeiiiiiaith
aeaioeii?aeeiaoiiai a?aoiiiaoae?aieea, iaae? yaea? eiio?iethaaeenue ca
aeiiiiiaith noa?aioaene/iiai aoeano (Paxinos & Watson, 1986).

Aeaeo?io?c?ieia?/i? aeine?aeaeaiiy. Aeey aeaioiaeaiiy *?INI in
situ (Suzue, 1984) aoei aeei?enoaii 167 o?e-/ioe?eaeiaiaeo uo?yo
e?i?? A?noa?. I?ae aeeaieei ao??iei ia?eicii i?iaiaeeee aei?naeueio
eai?iaeoiieth oa a?eaoa?aeueiee ia?a??c aei?naeueieo nieiiiiiceiaeo
ei??ioe?a. Aeae? ?ice?eaaee aaio?aeueio iiaa?oith noaieo iiceo, yeee
ia?a??caee ca ??aiai aeoiaeo ei??ioe?a n. abducens. A?aei?aia?iaoaaee
i?aaee ae?ao?aaiaeueiee ia?a. I?ney i?iaaaeaiiy aaio?aeueii?
eai?iaeoii?? nieiiee iicie ia?a??caee ca ??aiai N6-N7. O aeayeeo
aenia?eiaioaeueieo na??yo i?iaiaeeee iiia?a/i? ia?a??ce AEAAeI ca
?ino?aeueiith iaaeith ei??ioe?a IX-X ia? /a?aiiiiiceiaeo ia?a?a — i?ae
oaii/ooeeaeie ciiaie I ? S. Ca?aeii aeaiei e?oa?aoo?e (Ia?/aiei oa
?i., 1995), ia?a??ce ca oeei ??aiai i?ecaiaeyoue aei noeioeyoe??
/anoioe ?? o ae?ao?aaiaeueiiio ia?a? *?INI uo?yo ia?oeo aei?a aeeooy.
Aeaeo?e/io aeoeai?noue o ae?ao?aaiaeueiiio ia?a? (??) a?aeaiaeeee
a?iiey?ii, i?aeneethaaee (eiao?oe??io i?aeneeaiiy 104-105 ),
aeene?ei?ioaaee oa ?ioaa?oaaee ca aeiiiiiaith aiie?ooaeii-/anoioiiai
?ioaa?aoi?o c iino?eiith /ano 30.0 in. ?ioaa?iaai? neaiaee iiaeaaaee
ia 12-?ic?yaeiee aiaeiai-oeeo?iaee ia?aoai?thaa/ (AOeI), c’?aeiaiee c
ia?niiaeueiei eiii’thoa?ii.

Aeey noia?ooc?? aeei?enoiaoaaee iiaeeo?eiaaiee ?ic/ei E?aano
ianooiiiai neeaaeo (o i?e?iieyo ia 1 e ): NaCl — 124.0; KCl- 5.0;
KH2?I4 1.2; CaCl2 — 2.4; MgSO4- 1.3; NaHCO3 — 26.0; aetheica-30.0 (pH
7.4). O neeaae? oanooth/iai ?ic/eio c ?I 7.0 eiioeaio?aoe?th NaCl aoei
ca?eueoaii aei 140, a NaHCO3 — ciaioaii aei 10 i?e?iieue ia 1 e,
aeniiceoe?y aeaiiai ?ic/eio neeaaeaea 3 oa. ?ic/eie iane/oaaee
ea?aiaaiii (95% I2 + 5% NI2) i?ioyaii 10 oa i?e oaeaeeino? iiaea/?
aaciai? noi?o? 1 e/oa. A?iien?y iiaeaethaaeany aie?eaoe??th i?ioyaii
3 oa noia?oocoth/iai ?ic/eio, iane/aiiai ca oeo aea oiia aaciaith
noi?ooth, ui i?noeea 95% N2 ? 5% NI2. Oaeaee?noue noia?ooc?? neeaaeaea
4.0 ie/oa i?e 26.5 oN. I?ioyaii aenia?eiaio?a i?iaiaeeeiny aei??aiiy
?I2 ? ?I noia?oocoth/iai ?ic/eio, a oaeiae i?e?ii?ia ?ic/eio,
a?ae?a?aieo aaciina?aaeiuei ia aaio?aeuei?e iiaa?oi? aeiaaanoiai
iiceo, ca aeiiiiiaith i?e?iaiae?caoi?o (pH/Blood Gas Analyzer,
Type OP-215 «Radelkis», Oai?ueia). O na?aaeiueiio ?I2 o ?ic/ei? iaae
iiceii neeaaeaei 431± 34 ii ?o. no. o eiio?ie? oa 36± 9 ii ?o.no. ca
oiia a?iiene/iiai oanoo. Na?aaei? cia/aiiy ?I ?ic/eio neeaaeaee
7.34±0.09 o eiio?ie?, 7.30±0.11 i?e a?iien?? oa 7.01±0.06 aeey
oanooth/iai ?ic/eio c? cieaeaiei ?I.

A ?iaio? canoinoaaee: 1) eiieo?aioiee ?ia?a?oi? NO-neioace
iaoeeiaee ao?? NG-i?o?i-L-a?a?i?io (L-NAME) o eiioeaio?aoe?yo 1.0 oa
10.0 ieIieue/e; 2) ae/a/ee aaiiaeia?i, aaaio, ui ca’yco? NO (Hb), o
eiioeaio?aoe?? 0.30 ieIieue/e; 3) aeciaaii? aeiii?e NO i?o?ii?oneae
iao??th (SNP) ? i?o?iae?oea?ei o eiioeaio?aoe?yo 1.0 oa 10.0
ieIieue/e; 4) L-a?a?i?i, noano?ao a?ineioaco NO, o eiioeaio?aoe?yo
1.0 oa 10.0 ieIieue/e; 5) aaii?no a?aeiia?aeiiai oeio ?aoeaioi??a
NMDA o eiioeaio?aoe?? 5.0 ieIieue/e (an? ?aaeoeae ae?iaieoeoaa
«Sigma», NOA); 6)iaeiieo?aioiee aeieaoi? NMDA-?aoeaioi??a
2-(i?oi-oei?oai?e)-2-(iaoeeai?ii)-oeeeeiaaenai (eaoai?i, «Gedeon
Richter», Oai?ueia) o eiioeaio?aoe?yo 1.0, 10.0 oa 100.0 ieIieue/e.

Oanooth/? aeniiceoe?? (a?iiene/iiai ? aoeeaeioe/iiai ?ic/ei?a,
?ic/eio, ui i?noea NMDA) neeaaeaee 3 oa. A ie?aieo aenia?eiaioaeueieo
na??yo?o i?iaiaeeee i?ney 10 oa noia?ooc?? ?ic/eiii, ui i?noea iaeei ?c
aeine?aeaeoaaieo i?aia?ao?a, aai ?o eiia?iaoe?th. ?a?no?aoe?th ??
i?iaiaeeee i?ioyaii 9 oa (3 oa eiio?ieth, 3 oa — noia?ooc?y oanooth/ei
?ic/eiii ? 3 oa — a?aeieaaiiy). Ioe?ithaaee na?aaei? iieacieee
o?eaaeino? ?? (O?, in), ?o /anoioe (Fi, oa-1), aiie?ooaee (A, oiiai?
iaeeieoe?) oa eioaa?aeueii? ?ioaineaiino? (?, oiiai? iaeeieoe?). Iaeia
oiiaia iaeeieoey a?aeiia?aea? /anoio? 5 Aoe i?e aiieeooae? 5 ieA
?ioaa?iaaiiai neaiaeo ca iaeei oeeee ii?ino eaiaeo AOeI. Io?eiai?
?acoeueoaoe ia?iaeyee noaoenoe/ii ca aeiiiiiaith t-e?eoa??th
No’thaeaioa ( Ieioea? e ae?., 1991).

?acoeueoaoe aeine?aeaeaiue.

Aeine?aeaeaiiy NADPH-ae-?aaeoeaiino? iae?ii?a iaaeoey?ieo no?oeoo?,
i?e/aoieo aei aaia?aoe?? aeeoaeueiiai ?eoio, o iiaiia?iaeaeaieo uo?yo.
Cia/io e?euee?noue NADPH-ae-?aaeoeaieo iae?ii?a aoei ciaeaeaii ia an?o
?ino?ieao aeaeueieo ??aiyo aeiaaanoiai iiceo. Ia ?ino?aeueieo ??aiyo
iaea?eueo? iiioeyoe?? iiceoeaieo ioeueoeiiey?ieo ee?oei na?aaeiueiai
ae?aiao?o (15-25 iei) aoee aeyaeai? o ?icoaoiaaieo aaio?aeueii yae?ao
?aoeeoey?ii? oi?iaoe??. Iaea?eueoo u?euei?noue i?/aieo iae?ii?a (o
na?aaeiueiio 27.9±2.6 ee?oeiia 0.1 ii2) aeyaeee o eaoa?aeueiiio
ia?aa?aaioiee?oeiiiio (LPG?), ?ino?iaaio?ieaoa?aeueiiio ?aoeeoey?iiio
(o na?aaeiueiio 14.2±2.1 ee?oei ia 0.1 ii2) oa a?aaioiee?oeiiiio
yae?ao (o na?aaeiueiio 12.67± 1.2 ee?oeiia 0.1 ii2). Ia a?eueo
eaoaeaeueieo ??aiyo NADPH-ae-?aaeoeai?noue iae?ii?a niinoa??aaee o
aaio?aeueieo iaeanoyo ia?aiaae?aiiiai ?aoeeoey?iiai yae?a (o
na?aaeiueiio 10.1± 1.3 ee?oei ia 0.1 ii2) oa aaio?aeueiiio iaaeoey?iiio
?aoeeoey?iiio yae?? (o na?aaeiueiio 4.3 ± 0.7 ee?oei ia 0.1 ii2).A?oia
i?/aieo iae?ii?a iaeiai oa na?aaeiueiai ae?aiao?o i?enooiy oaeiae o
i?ii?aeiiio ?aoeeoey?iiio yae?? oa o ?ao?ioaoe?aeuei?e iaeano?. O
iaithaeiiio yae?? ia an?o eiai ?ino?ieaoaeaeueieo ??aiyo i?enooi?
iiiaeeiie? iiceoeai? ee?oeie (o na?aaeiueiio 2.9±0.3 ee?oei ia 0.1
ii2). Iiiaeeiie? i?/ai? iae?iie aeyaeaii oaeiae ia eaoaeaeueieo ??aiyo
a iaeano? iicaiaithaeiiai yae?a. Iiceoeai? ioeueoeiiey?i? iae?iie
na?aaeiueiai aeeaiao?o niinoa??aaee ia an?o ?ino?ieaoaeaeueieo ??aiyo
a yae?? iiiaeeiieiai o?aeoo, iaea?eueoo ?o u?euei?noue (o na?aaeiueiio
6.2±0.4 ee?oei ia 0.1 ii2) aeyaeee o aaio?ieaoa?aeueieo eiai iaeanoyo.
Iiiaeeiie? i?/ai? iae?iie ciaeaeai? a yae?? i?ae’yce/iiai ia?ao oa ?o
a?oie — a iaeano? aei?naeueiiai iioi?iiai yae?a aeoeath/iai ia?ao.
Oaeei /eiii, o uo?yo ia?oeo aei?a aeeooy NADPH-ae-?aaeoeai? iae?iie
?niothoue a on?o yae?ao Ae?A oa A?A, ui iiaea neeaaeaoe ii?oieia?/io
iniiao o/ano? NO a oeaio?aeuei?e ?aaoeyoe?? aeeoaeueiiai ?eoiiaaiaco o
iiaiia?iaeaeaieo uo?yo.

Aieea NO oa aeieoaaiiy NMDA-?aoeaioi??a ia aeaeo?e/io aeoeai?noue o
ae?ao?aaiaeueiiio ia?a? *?INI. Aie?eaoe?y 10.0 ieIieue L-NAME i?ecaaea
aei a??ia?aeiiai ca?eueoaiiy /anoioe (ia 23.4%) c? ciaiueoaiiyi
o?eaaeino? (ia 12.7%), aiie?ooaee (ia 14.0%) oa ?ioaa?aeueii?
?ioaineaiino? ?? (ia 11.1%). Ci?ie aiaeia?/ii? ni?yiiaaiino?
niinoa??aaee i?e aie?eaoe?? aaiiaeia?io (oaae. 1). I?ney
a?aeie?aieaiiy ?ino?aeueii? /anoeie AEAAeI /anoioa ?? i?e aie?eaoe??
10.0 ieIieue L-NAME ciaiooaaeany ia 29.4% (oaae. 1). Aie?eaoe?y
10.0 ieIieue L-a?a?i?io aeeeeeaea i?ioeeaaei? ci?ieia?aiao??a ??: ?o
o?eaae?noue, aiie?ooaea oa ?ioaa?aeueia ?ioaineai?noue a??ia?aeii
ca?eueooaaeeny (ia 7.0%, 18.1% e 15.8% a?aeiia?aeii), a /anoioa
ciaiooaaeany ia 6,2%. I?ney a?aeie?aieaiiy ?ino?aeueii? /anoeie
AEAAeI aie?eaoe?y L-a?a?i?io, iai?ioe, aeeeeeaea ca?eueoaiiy /anoioe ??
(oaae.1). Aie?eaoe?y 10.0 ieIieue i?o?iae?oea?eio i?ecaaea aei
a??ia?aeiiai ca?eueoaiiy aiie?ooaee oa ?ioaa?aeueii? ?ioaineaiino? ??
( ia 13.0% oa 16.9% a?aeiia?aeii) oa ciaioaiiy /anoioe ia 26.2%. O
eiioeaio?aoe?? 10.0

ieIieue ?ioee aeiii? NO, SNP, oaeiae aeeeeeaa cieaeaiiy /anoioe (ia
21.1%) oa ca?eueoaiiy aiie?ooaee oa ?ioaa?aeueii? ?ioaineaiino? (ia
14.9% e 17% a?aeiia?aeii). I?ney a?aeie?aieaiiy ?ino?aeueii? /anoeie
AEAAeI SNP aeeeeeaa ca?eueoaiiy /anoioe ?? (oaae.1). Oaeei /eiii,
aie?eaoe?y aaaio?a, ui aieeaathoue ia a?ineioac NO (L-NAME, L-a?a?i?i),
ui ca’ycothoue aiaeiaaiiee NO (Hb), a oaeiae aeciaaiieo aeiii??a NO
(i?o?iae?oea?ei, SNP) i?ecaiaeeoue aei a??ia?aeieo ci?i na?aaei?o
ia?aiao??a ?ioaa?iaaii? aeaeo?e/ii? aeoea

Oaae. 1. Aieea NO ia ia?aiao?e ??, ui aaia?othoueny *?INI
iiaiia?iaeaeaieo uo?yo c ?ioaeoiei aeiaaanoei iiceii oa i?ney
a?aeie?aieaiiy ?ino?aeueii? /anoeie AEAAeI (ciie I) oeyoii iiia?a/iiai
ia?a??co.

Oiiae aeine?aeo Ti, in Fi, oa-1 A,
oi.iae. I, oi. iae.

Eiio?ieue 799±27 6.49±0.24 104.4±4.6
4549±210

Eiio?ieue i?ney ia?a??co 672±16 13.93±0.37 82.3±2.2 3403±93

L-NAME, 10.0 ieIieue 698±23* 8.01±0.23* 89.8±6.3* 4044±131*

Oa ae, i?ney ia?a??co 581±19 9.83±0.26* 81.1±2.6
3239±150

Hb, 0.3 ieIieue 790±37 7.61±0.26* 93.8±5.4*
4438±505

Oa ae, i?ney ia?a??co 678±48 13.18±0.31 81.5±5.9
3336±492

L-a?a?i?i, 10.0 ieIieue 855±38* 6.09±0.41 123.3±6.2*
5268±497*

Oa ae, i?ney ia?a??co 685±50 20.26±3.68* 88.3±6.0
3573±635

SNP, 10.0 ieIieue 871±40* 5.12±0.23* 120.0±6.8*
5322±450*

Oa ae, i?ney ia?a??co 712±38 15.6±1.07* 84.8±5.7
3574±459

I?ei?oea. C??i/eaie iicia/aii noaoenoe/io a??ia?aei?noue a?aei?i
(P<0.05) a?ae eiio?ieueieo ia?aiao??a. iino? o ae?ao?aaiaeueiiio ia?a? *?INI, ui na?ae/eoue ia ei?enoue o/ano? NO o ?aaoeyoe?? oa?aeoa?enoee aeeoaeueiiai ?eoio o uo?yo ?aiiueiai a?eo ia iaaeoeini?iaeueiiio ??ai?. Aie?eaoe?y 1.0 ieIieue eaoai?io i?ecaaea aei iacia/iiai ca?eueoaiiy o?eaaeino? ?? oa a??ia?aeiiai ca?eueoaiiy ?o /anoioe ia 8.1%. I?ney a?aeie?aieaiiy ?ino?aeueii? /anoeie AEAAeI aiaeia?/ia aie?eaoe?y eaoai?io aeeeeeaea oaiaeaioe?th aei cieaeaiiy /anoioe ?? (ia 5.5%), oiae? ye ?o o?eaae?noue, aiie?ooaea oa ?ioaa?aeueia ?ioaineai?noue a??ia?aeii cieaeoaaeeny ia 15.7%, 24.7% oa 24.8% a?aeiia?aeii. Eaoai?i a eiioeaio?aoe?? 10.0 ieIieue/e i?ecaiaeea aei a??ia?aeiiai ca?eueoaiiy o?eaaeino? ?? ia 29.6%, aiie?ooaee oa ?ioaa?aeueii? ?ioaineaiino? ia 13.5% oa 30.0% a?aeiia?aeii, aiaeii/an c? ciaioaiiyi /anoioe ia 15.4%. I?ney a?aeie?aieaiiy ?ino?aeueii? /anoeie AEAAeI eaoai?i a aiaeia?/i?e eiioeaio?aoe?? ia aeeeeeaa ca?eueoaiiy o?eaaeino? oa ?ioaa?aeueii? ?ioaineaiino? ??, oiae? ye ?o aiie?ooaea ? /anoioa a??ia?aeii ciaiooaaeeny ia 25.4% oa 8.7% a?aeiia?aeii. Oaeei /eiii, aeey ca?eueoaiiy /anoioe ?? i?e aie?eaoe?? 1.0 ieIieue eaoai?io oa ?o o?eaaeino? i?e aie?eaoe?? 10.0 ieIieue oeueiai aaaioo iaiao?aeiith ? oe?e?ni?noue ca'yce?a c ?ino?aeueiith /anoeiith AEAAeI. I?e aie?eaoe?? 100.0 ieIieue eaoai?io a?aeaoaaeiny i?eai?/aiiy an?o ia?aiao??a ?? ye ca oiia ?ioaeoiiai AEAAeI, oae ? i?ney a?aeie?aieaiiy eiai ?ino?aeueii? /anoeie. Aieea NO ia ci?ie aeaeo?e/ii? aeoeaiino? o ae?ao?aaiaeueiiio ia?a? *?INI i?e ae?? NMDA. Aie?eaoe?y 5.0 ieIieue NMDA aeeeeeaea a??ia?aeia ca?eueoaiiy /anoioe ?? ia 49.1% (oaae. 2). Ia oe? iiia?aaeiuei? aie?eaoe?? 10.0 ieIieue L-NAME NMDA ia i?ecaiaeea aei a??ia?aeieo ci?i aoaeue-yeeo oa?aeoa?enoee ??. Iiia?aaeiy aie?eaoe?y Hb i?ecaiaeeea aei aiaeia?/i?o ?acoeueoao?a: i?ae /an ianooiii? aie?eaoe?? NMDA /anoioa ?? iaa?oue aeaui ciaiooaaeany. Ia oe? aie?eaoe?? 10.0 ieIieue L-a?a?i?io i?ae /an oanoo c NMDA an? na?aaei? ia?aiao?e ?? c?inoaee a?eueo nooo?ai, i?ae o ?ioaeoieo i?aia?ao?a ( /anoioa ca?eueooaaeany o 2.25 ?ace). Iiia?aaeiy aie?eaoe?y 10.0 ieIieue SNP ia aeeeeeaea ca?eueoaiiy /anoioe ?? i?e ianooii?e aie?eaoe?? NMDA, aea aeiaeaaaiiy Hb aei ?ic/eio c SNP i?ecaiaeeei aei iaeo?ae?caoe?? aeieoth/iai aieeao SNP ia /anoioo ?? i?ae /an oanoo c NMDA (oaae.2). Oaeei /eiii, aie?eaoe?y NMDA i?ecaiaeeea aei a??ia?aeiiai ca?eueoaiiy /anoioe ??. Ca oiia iiia?aaeiueiai aeieoaaiiy NO-neioace aai ca'ycoaaiiy aiaeiaaiiiai NO oey ?aaeoeey aeieoaaeany; aie?eaoe?y L-a?a?i?io, iai?ioe, noeioethaaea ??. Aieea NO oa aeieoaaiiy NMDA-?aoeaioi??a ia aeaeo?e/io aeoeai?noue o ae?ao?aaiaeueiiio ia?a? *?INI i?e a?iien?? oa i?e cieaeaii? ?I ciai?oiueiee?oeiii? ??aeeie. A?iiene/iee oano aeeeeeaa o ?ioaeoieo i?aia?ao?a ii/aoeiaa iacia/ia ca?eueoaiiy /anoioe ??, yea oaeaeei ci?ithaaeiny ia iii?oia ?? i?eai?/aiiy. Na?aaeiy /anoioa i?ioyaii onueiai oanoo aoea a??ia?aeii ieae/ith ia 23.2% ca eiio?ieueio (oaae. 3). E??i oiai, i?e a?iien?? niinoa??aaee oaiaeaioe?th aei ca?eueoaiiy o?eaaeino?, aiie?ooaee oa ?ioaa?aeueii? ?ioaineaiino? ??. A?iiene/iee oano ia oe? aie?eaoe?? 10.0 ieIieue L-NAME aeeeeeaa a??ia?aeia ca?eueoaiiy /anoioe ?? ia 66.8% ?acii ?c a??ia?aeiei ciaiueoaiiyi o?eaaeino? (ia 14.2%), aiie?ooaee ( ia 10.4%) oa ?ioaa?aeueii? ?ioaineaiino? ?? (ia 17.8%). Iiia?aaeiy aie?eaoe?y 10.0 Oaae. 2. Aieea NO ia ia?aiao?e ??, ui aaia?othoueny *?INI, i?e aie?eaoe?? NMDA. Oiiae aeine?aeo Ti, in Fi, oa-1 A, oi. iae. I, oi. iae. 1.Eiio?ieue 771±27 6.60±0.18 104.8±5.1 4558±217 NMDA, 5.0 ieIieue 788±23 9.84±0.53* 108.6±3.4 4778±178 2.L-NAME, 10.0 ieIieue 720±21+ 6.68±0.25 90.1±2.7+ 3842±129+ NMDA, 5.0 ieIieue 750±23 6.88±0.34+ 89.8±2.8+ 3996±143+ 3.Hb, 0.3 ieIieue 765±40 7.34±0.34+ 78.8±3.5+ 3617±405+ NMDA, 5.0 ieIieue 691±40+ 6.82±0.32+ 77.4±3.5+ 3303±435+ 4.L-a?a, 10.0 ieIieue 909±36+ 5.18±0.34+ 126.3±5.2+ 4820±369+ NMDA, 5.0 ieIieue 951±84+ 11.66±2.22* 136.0±10.4+ 5249±1150 5. SNP, 10.0 ieIieue 879±33+ 6.10±0.26 120.5±5.8+ 5330±0779+ NMDA, 5.0 ieIieue 850±58+ 6.00±0.53+ 132.2±6.9*+ 5581±822+ 6. SNP, 10.0 ieIieue+ +Hb, 0.3 ieIieue 657±34+ 6.26±0.31 111.8±7.0+ 3557±410+ NMDA, 5.0 ieIieue 708±25+ 9.08±0.42* 121.0±7.4+ 3985±353* I?ei?oea. C??i/eaie iicia/aii noaoenoe/io a??ia?aei?noue a?aei?i (P<0.05) a?ae eiio?ieueieo ia?aiao??a, o?anoeeaie - a??ia?aei?noue a?aei?i ia?aiao??a o a?oiao 2-6 a?ae aiaeia?/ieo o a?oi? 1. ieIieue L-a?a?i?io i?ae /an a?iiene/iiai oanoo i?ecaiaeeea aei a?eueo ae?aaeaiiai, i?ae o ?ioaeoieo *?INI, ciaioaiiy /anoioe (ia 31.4%), aea aiie?ooaea oa ?ioaa?aeueia ?ioaineai?noue ?? i?e a?iien?? c?inoaee a?eueoa, i?ae o eiio?ie? (ia 7.0% e 12.0% a?aeiia?aeii). Iiia?aaeiy aie?eaoe?y 10.0 ieIieue SNP i?ecaiaeeea aei iaio ae?aaeaiiai, i?ae o ?ioaeoieo i?aia?ao?a,i?eai?/aiiy /anoioe ?? i?e ianooii?e a?iien?? (ia 5.7%), a o?eaae?noue oa ?ioaa?aeueia ?ioaineai?noue ?? iii?oii ca?eueooaaeeny ii??aiyii c eiio?ieai (ia 14.6% oa 17.3% a?aeiia?aeii, oaae. 3). O?eaaea (10 oa) iiia?aaeiy aie?eaoe?y 10.0 ieIieue eaoai?io aeeeeeaea ae?aaeaia ciaioaiiy an?o eiio?ieueieo iieaciee?a ??. I?ae /an ianooiiiai Oaae. 3. Aieea NO oa aeieoaaiiy NMDA-?aoeaioi??a ia ia?aiao?e ??, ui aaia?othoueny *?INI, i?e a?iien??. Oiiae aeine?aeo Ti, in Fi, oa-1 A, oi. iae. I, oi. iae. 1.Eiio?ieue 810±34 6.47±0.27 94.6±4.3 4273±227 a?iien?y 841±60 4.97±0.48* 96.7±8.7 4492±412 2.L-NAME, 10.0 ieIieue 663±41+ 6.68±0.31 69.4±2.3+ 2932±118+ a?iien?y 569±62*+ 11.14±1.02* 62.2±7.0*+ 2409±360*+ 3.L-a?a, 10.0 ieIieue 1061±35+ 5.99±0.29 119.2±6.4+ 6025±318+ a?iien?y 1087±84+ 4.11±0.35*+ 127.5±7.5+ 6748±714*+ 4. SNP, 10.0 ieIieue 1029±28+ 5.43±0.25+ 91.7±5.0 5213±340+ a?iien?y 1180±77* 5.12±0.41 90.9±8.2 6120±830*+ 5.Eaoai?i,10.0 ieIieue 426±14+ 4.92±0.20+ 65.2±7.0+ 1881±76+ a?iien?y 372±39*+ 3.76±1.08 58.4±11.0+ 1512±275*+ I?ei?oea. C??i/eaie iicia/aii noaoenoe/io a??ia?aei?noue a?aei?i (P<0.05) a?ae eiio?ieueieo ia?aiao??a, o?anoeeaie - a??ia?aei?noue a?aei?i ia?aiao??a o a?oiao 2-5 a?ae aiaeia?/ieo o a?oi? 1. a?iiene/iiai oanoo o?eaae?noue ?? ciaiooaaeany ia 12.7%, a ?o aiie?ooaea oa ?ioaa?aeueia ?ioaineai?noue - ia 10.4% oa 19,6% a?aeiia?aeii. Aea /anoioa ?? ciaiooaaeany ia 23.5%, ui i?aeoe/ii ia a?ae??ciy?oueny a?ae ?aaeoe?? ?ioaeoieo *?INI ia a?iien?th (oaae. 3). Aiae?c ci?ie oeueiai iieacieea o ia?oee oa ae?oaee 90-naeoiaeiee ?ioa?aae a?iiene/iiai oanoo iieacaa, ui aieea a?iien?? ia oe? eaoai?io i?ecaiaeea o ia?o? 90 n aei a??ia?aeiiai ciaioaiiy /anoioe ia 23.0%, oiae? ye o ?ioaeoieo *?INI /anoioa o oeae /an iacia/ii ca?eueoo?oueny. O ae?oa?e iieiaei? oanoo a?aeaoaaeiny iiaeaeueoa ciaiueoaiiy /anoioe, aea ?? cia/aiiy i?ney aie?eaoe?? eaoai?io aoei aeaui aeuei ca aiaeia?/iee iieaciee eiio?ieueiiai a?iiene/iiai oanoo. Eaoai?i o eiioeaio?aoe?? 100.0 ieIieue/e i?e ianooii?e a?iien?? o a?eueo?e /anoei? aeine?ae?a i?ecaiaeea aei iiaiiai cieeiaiiy aeeoaeueii? aeoeaiino? o ae?ao?aaiaeueiiio ia?a? *?INI. Oaeei /eiii, aeieo aaiiy NO-neioace i?e ianooii?e a?iien?? i?ecaiaeeoue aei ciaioaiiy o?eaaeino?, aiie?ooaee oa ?ioaa?aeueii? ?ioaineaiino? ?? c? no?eeei ca?eueoaiiyi ?o /anoioe. Aie?eaoe?? L-a?a?i?io oa SNP i?ecaiaeeee aei iii?oiiai ca?eueoaiiy o?eaaeino? oa ?ioaa?aeueii? ?ioaineaiino? ?? i?e a?iien?? ii??aiyii c ?ioaeoieie *?INI. SNP ni?eya oaeiae ii??aiyii iaioiio i?eai?/aiith /anoioe ?? i?e a?iien??. Aeieoaaiiy NMDA-?aoeaioi??a i?e ianooii?e a?iien?? i?ecaiaeeoue aei ciaioaiiy an?o ia?aiao??a ??, aiane?aeie /iai iiaea a?aeaoaaoeny iiaia aaeueioaaiiy aeeoaeueiiai ?eoio *?INI. Noia?ooc?y *?INI ?ic/eiii c ?I 7.0 aeeeeeaea a??ia?aeia ca?eueoaiiy /anoioe ?? ia 27%, a ?o aiie?ooaea oa ?ioaa?aeueia ?ioaineai?noue ciaiooaaeeny ia 10% e 10.5% a?aeiia?aeii. Ca oiia iiia?aaeiuei? aie?eaoe?? 10.0 ieIieue L-NAME i?e ianooiiiio aieea? ?ic/eio c ?I 7.0 /anoioa ?? a??ia?aeii ia ci?ithaaeany. Ia oe? aie?eaoe?? 10.0 ieIieue L-a?a?i?io cieaeaiiy ?I ?ic/eio aei 7.0 i?ecaiaeeei aei ae?aaeaiiai oa o?eaaeiai ca?eueoaiiy /anoioe ?? , ?o aiie?ooaee oa ?ioaa?aeueii? ?ioaineaiino?. Aie?eaoe?y ?ic/eio c ?I 7.0 i?ney ia?iaee *?INI 10.0 ieIieue SNP ia aeeeeeaea a??ia?aeiiai ca?eueoaiiy /anoioe ??. Ia oe? aie?eaoe?? eaoai?io noia?ooc?y ?ic/eiii c ?I 7.0 i?ecaiaeeea aei ei?ioei/aniiai ca?eueoaiiy /anoioe ?? (ia 22. 5% oa 19% i?e aie?eaoe?? 10.0 oa 100.0 ieIieue eaoai?io a?aeiia?aeii), a ?o aiie?ooaea oa ?ioaa?aeueia ?ioaineai?noue a??ia?aeii ia ci?ithaaeeny. Oaeei /eiii, L-NAME, eaoai?i oa SNP ciaioothoue ?aaeoe?th aeeoaeueiiai ?eoio *?INI ia cieaeaiiy ?I noia?oocoth/iai ?ic/eio, a L-a?a?i?i noeioeth? aeaio ?aaeoe?th. Iaaiai?aiiy ?acoeueoao?a. Ia i?aenoaa? io?eiaieo ?acoeueoao?a ie i?eionea?ii, ui LPGi ? iaea?eueo nooo?aei aeaea?aeii a?ineioaco NI, yeee aieeaa? ia aaia?aoe?th aeeoaeueiiai ?eoio iae?iiaie A?A o iiaiia?iaeaeaieo uo?yo. Aeayeei i?aeoaa?aeaeaiiyi oeueiio iiaea aooe ?nioaaiiy a aeaiiio yae?? o aei?ineeo uo??a aaeeei? a?oie NI-neioaci?ioii?aaeoeaieo iae?ii?a (Dun et al.,1994). A iae?iiao oeueiai oeio ii??aiyii c ee?oeiaie, ui ia i?noyoue NO-neioaco, ciaeaeaii a?eueoo u?euei?noue NMDA-?aoeaioi??a (Price et al., 1993). A?aeiii (Funk et al., 1993), ui o/anoue NMDA-?aoeaioi??a o iiaiia?iaeaeaieo uo?yo ia ? iaiao?aeiith aeey aaia?aoe?? aeeoaeueiiai ?eoio iiia?a/ieie iaaeoey?ieie c??caie 400 iei caaoiaoee ia ??ai? i?a-Aaooeeiaa?iaa eiiieaena. Ca oiia oeueiai i?aia?aoo a?eueo ?ino?aeuei? a?aeae?ee A?A, o oiio /ene? ? LPGi, aacoiiaii, ia a?aee o/anoue o ?eoiiaaiac?. ?acoeueoaoe iaoeo aeine?ae?a na?ae/aoue ia ei?enoue o/ano? NMDA-?aoeaioi??a o ?aaoeyoe?? ia?aiao??a aeeoaeueiiai ?eoio *?INI, ui ni?aiaaea? c ?acoeueoaoaie, io?eiaieie ia aei?ineeo uo?ao in vivo i?e canoinoaaii? a?eueo niaoeeo?/ieo aioaaii?no?a NMDA (Monteau et al., 1990). A iao?e ?iaio? iaea?aeaii aeai? i?i o/anoue aiaeiaaiiiai NO o oii?/iiio aaeuei?aiiio eiio?ie?, yeee cae?enith?oueny ?ino?aeueieie a?aeae?eaie AEAAeI o iiaiia?iaeaeaieo uo?yo. A?aeiii (Ogawa et al., 1995), ui NI cae?aiee ca?eueooaaoe aea?eueiaiiy aeooaiaoo a iaaeoey?ieo no?oeoo?ao, a iaeiei c iae?iiaae?aoi?ieo iaoai?ci?a oii?/iiai aaeueioaaiiy ?eoio, ui ?nio? o ?ino?aeueiiio AEAAeI, ? aeooaiaoa?a?/iee (Dillon et al., 1991). Aea a a?eueo eaoaeaeueiiio AEAAeI, aea ?icoaoiaaiee aeeoaeueiee aaia?aoi? (Smith et al., 1991), aieea aeooaiaoo ia ??ci? oeie ?aoeaioi??a oa aeeeeeaiee aiane?aeie aeoeaaoe?? NMDA-?aoeaioi??a a?ineioac NI iiaea noeioethaaoe aeeoaeueiee ?eoi. Iiaeeeai, NMDA-?aoeaioi?e aaciina?aaeiuei ia aa?ooue o/ano? a ooieoe?iioaaii? ?eoiiaaia?oth/i? ia?aae? iae?ii?a, aea a?aeiia?aeathoue ca iaaeoiaeaeaiiy aei ia? oii?/iiai aeoeaoth/iai aieeao a?ae iae?ii?a ?aoeeoey?ii? oi?iaoe?? oa oaii?aoeaioi?ieo no?oeoo? AEAAeI, a NI, ui ooai?th?oueny i?e aeoeaaoe?? NMDA-?aoeaioi??a, i?aeneeth? aeoeaoth/ee neaiae oeyoii ca?eueoaiiy aea?eueiaiiy aeooaiaoo oa aeoeaaoe?? iaNMDA-?aoeaioi??a, ui aaciina?aaeiuei aa?ooue o/anoue o aaia?aoe?? aeeoaeueiiai ?eoio (Funk et al., 1993). E??i oiai, a?aeiii, ui NMDA oa NO iiaeooue ca?eueooaaoe aea?eueiaiiy aoeaoeeoie?io a iiceo (Ohkuma et al., 1995; Leonard & Lydic, 1995), a oie?ia?a?/i? iaoai?cie ? i?ia?aeieie o iaaeoey?i?e oaii/ooeeaino? aeeoaiiy (Fukuda & Loeschcke, 1979). O iaoai?ciao ciaioaiiy /anoioe aeeoaeueiiai ?eoio i?e a?iien?? a iao?o aeine?aeao iiaea a?aoe o/anoue aiaeiaaiiee NO ca ?aooiie i?yiiai aeieoth/iai aieeao ia eaiaeuei? oa ?aoeaioi?i? no?oeoo?e ?ani??aoi?ieo iae?ii?a, a oaeiae aeoeaaoe?? oii?/iiai aaeueioaaiiy ?ino?aeueieie a?aeae?eaie AEAAeI. O iiaiia?iaeaeaieo oey ?aaeoe?y, iiaeeeai, ? aaeaioeaiith, oiio ui cieaeaiiy iaoaaie?cio i?e i?eai?/aii? aeoeaiino? ?ani??aoi?ieo iae?ii?a ni?ey? caa?aaeaiith ?o aeeoo?caeaoiino? i?e iieiaiaiio a?iiene/iiio no?an? (Cherniack et al., 1995). AENIIAEE 1. ?ieue NO a oeaio?aeuei?e ?aaoeyoe?? aeeoaiiy oa ?iciiae?eaiiy iae?ii?a, ui i?noyoue NO-neioaco, a no?oeoo?ao iaaeoey?iiai aaia?aoi?a aea/aeeny eeoa a aenia?eiaioao ia aei?ineeo oaa?eiao ? ia aea/ai? o iiaiia?iaeaeaieo; cia/aiiy NMDA-?aoeaioi??a o aeeoaeueiiio ?eoiiaaiac? o oeeo oaa?ei inoaoi/ii ia c'yniaaii. Aeooaeuei?noue iaoiai aeine?aeaeaiiy iaaeoey?ieo iaoai?ci?a o/ano? NO ? NMDA-?aoeaioi??a o ?aaoeyoe?? aeeoaeueiiai ?eoiiaaiaco o iiaiia?iaeaeaieo uo?yo iia'ycaia c iaiao?aei?noth aea/aiiy i?e/ei ii?ooaiue oeaio?aeueii? ?aaoeyoe?? ooieoe?? aeeoaiiy a iaiiaoaeueiiio ia??iae?. 2. Aeine?aeaeaii ?iciiae?e iae?ii?a, ui i?noyoue NADPH-ae?aoi?aco (ia?ea? NO-neioace) o no?oeoo?ao aaia?aoi?a aeeoaeueiiai ?eoio uo?yo ia?oeo aei?a aeeooy. A aenia?eiaioao ia /anoeiai ?cieueiaaieo ooo/ii noia?oociaaieo iaaeoeini?iaeueieo i?aia?aoao uo?yo ia?oeo aei?a aeeooy iieacaii o/anoue NO oa NMDA-?aoeaioi??a caoaeaeoth/eo ai?iieeneio o ?aaoeyoe?? ia?aiao??a ?ioaa?iaaii? aeaeo?e/ii? aeeoaeueii? aeoeaiino? o ae?ao?aaiaeueiiio ia?a? o ii?i?, i?e a?iien?? oa i?e cieaeaii? ?I ciai?oiueiee?oeiiiai ?ic/eio. 3. NADPH-ae?aoi?aci?aaeoeai? iae?iie ciaeaeai? a on?o a?aeiieo yae?ao aei?naeueii? oa aaio?aeueii? ?ani??aoi?ieo a?oi iae?ii?a aeiaaanoiai iiceo /ioe?eaeaiieo uo?yo, iaeneiaeueia na?aaeiy u?euei?noue i?/aieo iae?ii?a (27.9±2.6 ee?oei ia 0.1 ii2) iieacaia o ?ino?aeuei?e /anoei? aaio?ieaoa?aeueiiai a?aeae?eo aeiaaanoiai iiceo - a iaeano? eaoa?aeueiiai ia?aa?aaioiee?oeiiiai yae?a. 4. NO iiina?aaeeiao? iaoai?ci oii?/iiai aaeueioaaiiy /anoioe aeeoaeueiiai ?eoio, ui cae?enith?oueny ?ino?aeueiith /anoeiith aaio?ieaoa?aeueiiai a?aeae?eo aeiaaanoiai iiceo o iiaiia?iaeaeaieo uo?yo, a oaeiae oi?ioaaiiy /anoioii-aiie?ooaeieo oa?aeoa?enoee aeeoaeueiiai ?eoio, yeee aaia?o?oueny no?oe-oo?aie, ui ?icoaoiaai? a?eueo eaoaeaeueii. 5. NMDA-?aoeaioi?e aa?ooue o/anoue o iaoai?ciao oii?/iiai aaeueioaaiiy /anoioe aeeoaeueiiai ?eoio oa aaeueioaaiiy o?eaaeino? ?ini??aoe??, ui cae?eniththoueny ?ino?aeueiith /anoeiith aaio?ieaoa?aeueiiai a?aeae?eo aeiaaanoiai iiceo iiaiia?iaeaeaieo uo?yo. 6. Aiaeiaaiiee NO iiina?aaeeiao? aieea aeciaaiiiai NMDA, ui aie?eo?oueny ia aaio?aeueio iiaa?oith aeiaaanoiai iiceo iaaeoeini?iaeueieo i?aia?ao?a iiaiia?iaeaeaieo uo?yo, aea aie?eaoe?y aeiii?a NO i?o?ii?oneaeo iao??th i?ecaiaeeoue aei aeieoaaiiy noeioeyoe?? /anoioe aeeoaeueiiai ?eoio i?e ae?? NMDA. Aeaiee aieea i?o?ii?oneaeo iao??th iia'ycaiee c aeieoth/ith ae??th iaaeeeoeo NO ia NMDA-?aoeaioi?e, oiio ui ciaioo?oueny i?e aeiaeaaaii? aaiiaeia?io, ui ca'yco? NO. 7. Ca oiia a?iiene/iiai oanoo aiaeiaaiiee NO aa?a o/anoue o iaoai?ci? i?eai?/aiiy /anoioe aeeoaeueiiai ?eoio oa caa?aaeaii? iaiao?aeiiai ??aiy aiie?ooaee oa ?ioaa?aeueii? ?ioaineaiino? ?ini??aoi?ieo ?ic?yae?a, ui aaia?othoueny iaaeoeini?iaeueieie i?aia?aoaie iiaiia?iaeaeaieo uo?yo. Iiia?aaeiy aie?eaoe?y i?o?ii?oneaeo iao??th ni?ey? a?aeiinii iaioiio i?eai?/aiith /anoioe oa ca?eueoaiith ?ioaa?aeueii? ?ioaineaiino? ?ini??aoi?ieo ?ic?yae?a ca oiia a?iien??. 8. Aeieoaaiiy NMDA-?aoeaioi??a i?e ianooii?e a?iien?? i?ecaiaeeoue aei a?eueo ae?aaeaiiai i?eai?/aiiy ia?aiao??a aeeoaeueiiai ?eoio, ui aaia?o?oueny iaaeoeini?iaeueieie i?aia?aoaie iiaiia?iaeaeaieo uo?yo. 9. Aiaeiaaiiee NO iiina?aaeeiao? noeioeyoe?th /anoioe aeeoaeueiiai ?eoio, ui aaia?o?oueny iaaeoeini?iaeueieie i?aia?aoaie iiaiia?iaeaeaieo uo?yo, yea a?aeaoaa?oueny aiane?aeie aeoeaaoe?? oaii?aoeaioi??a aaio?aeueii? iiaa?oi? aeiaaanoiai iiceo noia?oocoth/ei ?ic/eiii c ?I 7.0. Aeiii? NO i?o?ii?oneae iao??th ciaioo? aeaio noeioeyoe?th, iiaeeeai, aiane?aeie aeieoaaiiy NMDA-?aoeaioi??a. 10. Aeieoaaiiy NMDA-?aoeaioi??a i?ecaiaeeoue aei ciaioaiiy noeioeyoe?? /anoioe aeeoaeueiiai ?eoio, ui aaia?o?oueny iaaeoeini?iaeueieie i?aia?aoaie iiaiia?iaeaeaieo uo?yo, i?e ae?? ?ic/eio c ?I 7.0, ui na?ae/eoue i?i o/anoue aeaiiai oeio ?aoeaioi??a o iaaeoey?i?e oaii/ooeeaino? aeeoaiiy. IA?AE?E I?AOeUe, IIOAE?EIAAIEO CA OAIITH AeENA?OAOe?? 1. Aieaei Ae.A., Ia?/aiei A.A., Na?aaeaiei I.I. Aeeyiea ieneaea acioa ia ?anie?aoi?ioth aeoeaiinoue, aaia?e?oaioth iaaeoeeinieiaeueiuie i?aia?aoaie e?unyo ?aiiaai aic?anoa a oneiaeyo aeiienee // Iae?ioeceieiaey/Neurophysiology. - 1997. - o. 29, N 6. - N. 420-430. 2. Aieaei Ae.A. O/anoea ieneaea acioa a ?aaeecaoeee aeeyiey NMDA ia ?anie?aoi?iue ?eoi, aaia?e?oaiue iaaeoeeinieiaeueiuie i?aia?aoaie iiai?iaeaeaiiuo e?unyo // Iae?ioeceieiaey/Neurophysiology. - 1998. - o. 30, N1. - N. 59-67. 3. Aieaei Ae.A., Ia?/aiei A.A., Na?aaeaiei I.I., Aaneeaiei Ae.A. O/anoea NMDA-?aoeaioi?ia a ?aaoeyoeee ?anie?aoi?iiai ?eoia, aaia?e?oaiiai iaaeoeeinieiaeueiuie i?aia?aoaie e?unyo ia?auo aeiae aeecie // Iae?ioeceieiaey/Neurophysiology. - 1998. - o. 30, N 2. - N. 129-135. 4. Aiea?i Ae.A. O/anoue NMDA-?aoeaioi??a ? ieneaeo acioo a ?aaeoe?yo iaaeoey?iiai ?ani??aoi?iiai aaia?aoi?a uo?yo ?aiiueiai a?eo ia a?iien?th oa aoeeaeic // Iae?ioeceieiaey/Neurophysiology. - 1998. o. 30, N 6. - N.483-487. 5. Aiea?i Ae.A., E?anthe I.I. Aieea i?o?iae?oea?eio ia ?ani??aoi?io aeoeai?noue, ui aaia?o?oueny iaaeoeini?iaeueieie i?aia?aoaie iiaiia?iaeaeaieo uo?yo // O?c?ieia?/iee aeo?iae. - 1998. - o. 44, N 3. - N. 133-134. 6. Na?aaeaiei I.I., Aiea?i Ae.A. O/anoue NMDA-?aoeaioi??a o ?aaoeyoe?? ?ani??aoi?ii? aeoeaiino?, yea aaia?o?oueny /anoeiai ?cieueiaaieie iaaeoeini?iaeueieie i?aia?aoaie iiaiia?iaeaeaieo uo?yo i?e a?iien?? // O?c?ieia?/iee aeo?iae. - 1998. - o. 44, N 3. - N. 148-149. 7. Aieaei Ae.A. Aeooaiaoa?ae/aneee eiio?ieue ?anie?aoi?iiai ?eoia iiai?iaeaeaiiuo e?unyo i?e aeiienee // Aeiieney: aeano?oeoeaiia e eiino?oeoeaiia aeaenoaea: Iaoa?eaeu Iaaeaeoia?. eiio. - Eeaa, 1998. - N. 51-52. 8. Aiea?i Ae., Na?aaeaiei I. Aieea ?I ciai?oiueiee?oeiiiai ?ic/eio ia iaaeoey?iee aeeoaeueiee ?eoi uo??a ia?oeo aei?a aeeooy: cia/aiiy NMDA ?aoeaioi??a // I?iaeaie a?eiai? o?c?ieia??: Iaoa??aee anaoe?. eiio. -Eooeuee, 1998. - N. 37. 9. Aieaei Ae.A., Na?aaeaiei I.I. O/anoea iiiiieneaea acioa a ?aaoeyoeee ?anie?aoi?iiai ?eoia, aaia?e?oaiiai iaaeoeeinieiaeueiuie i?aia?aoaie e?unyo ?aiiaai aic?anoa // ?ieue iiiiieneaea acioa a i?ioeannao aeeciaaeayoaeueiinoe. - Ieine, 1998. - N. 24-26. Aiea?i Ae.A. Aeine?aeaeaiiy iaaeoey?ieo iaoai?ci?a o/ano? ieneaeo acioo oa ?aoeaioi??a N-iaoee-D-ania?oaoo a ?aaoeyoe?? aeeoaeueiiai ?eoiiaaiaco o iiaiia?iaeaeaieo uo?yo. -?oeiien. Aeena?oaoe?y ia caeiaoooy iaoeiaiai nooiaiy eaiaeeaeaoa a?ieia?/ieo iaoe ca niaoe?aeuei?noth 03.00.13 - o?c?ieia?y ethaeeie ? oaa?ei. - ?inoeooo o?-c?ieia?? ?i. I.I. Aiaiiieueoey IAI Oe?a?ie, Ee?a, 1999. A aenia?eiaioao ia iiaiia?iaeaeaieo uo?yoao aea/aee ?iciiae?e iae?ii?a, ui i?noyoue NADPH-ae?aoi?aco (ia?ea? iae?iiaeueii? NO-neioace) o no?oeoo?ao iaaeoey?iiai aeeoaeueiiai aaia?aoi?o, a oaeiae ?ieue NO oa NMDA-?aoeaioi??a caoaeaeoth/eo ai?iieeneio o ?aaoeyoe?? aeeoaeueii? aeoeaiino? o ae?ao?aaiaeueiiio ia?a? ooo/ii noia?oociaaieo /anoeiai ?cieueiaaieo iaaeoeini?iaeueieo i?aia?ao?a. NADPH-ae?aoi?aci?aaeoeai? iae?iie ciaeaeai? a on?o yae?ao aei?naeueii? oa aaio?aeueii? ?ani??aoi?ieo a?oi iae?ii?a, ?o iaeneiaeueio u?euei?noue aeyaeaii o ?ino?aeuei?e /anoei? aaio?ieaoa?aeueiiai a?aeae?eo aeiaaanoiai iiceo (AEAAeI) - a iaeano? eaoa?aeueiiai ia?aa?aaioiee?oeiiiai ?aoeeoey?iiai yae?a. Anoaiiaeaii, ui aiaeiaaiiee NO iiina?aaeeiao? iaoai?ci oii?/iiai aaeueioaaiiy /anoioe aeeoaeueiiai ?eoio (Ae?), yeee ?nio? o ?ino?aeuei?e /anoei? AEAAeI, o ii?i? oa i?e a?iien??, aeoeaaoe?th /anoioe Ae? i?e cieaeaii? ciai?oiueiee?oeiiiai ?I, a oaeiae aa?a o/anoue o oi?ioaaii? aacaeueiiai Ae? a?eueo eaoaeaeueieie no?oeoo?aie AEAAeI. Iieacaii, ui oiiaith ?aae?caoe?? aieeao NMDA ia Ae? ? a?ineioac NO, aea inoaii?e iiaea aeieoaaoe NMDA-?aoeaioi?e. NMDA-?aoeaioi?e AEAAeI aa?ooue o/anoue o ?aaoeyoe?? ia?aiao??a Ae? o ii?i?, i?e a?iien?? oa i?e cieaeaii? ciai?oiueiee?oeiiiai ?I. Eeth/ia? neiaa: NO, NO-neioaca, NMDA, NADPH-ae?aoi?aca, ?I, aeeoaeueiee ?eoi, /anoeiai ?cieueiaaiee iaaeoeini?iaeueiee i?aia?ao, aaio?ieaoa?aeueiee a?aeae?e aeiaaanoiai iiceo, a?iien?y. Aieaei Ae.A. Enneaaeiaaiea iaaeoeey?iuo iaoaieciia o/anoey ieneaea acioa e ?aoeaioi?ia N-iaoee-D-ania?oaoa a ?aaoeyoeee aeuoaoaeueiiai ?eoiiaaiaca o iiai?iaeaeaiiuo e?unyo. -?oeiienue. Aeenna?oaoeey ia nieneaiea o/aiie noaiaie eaiaeeaeaoa aeieiae/aneeo iaoe ii niaoeeaeueiinoe 03.00.13 - oeceieiaey /aeiaaea e aeeaioiuo. - Einoeooo oeceieiaee ei. A.A. Aiaiiieueoea IAI Oe?aeiu, Eeaa, 1999. N iiiiuueth aenoioeie/aneiai iaoiaea enneaaeiaaii ?ani?aaeaeaiea iae?iiia, niaea?aeaueo NADPH-aeeaoi?aco (NADPH-ae, ia?ea? neioacu ieneaea acioa) a no?oeoo?ao aaia?aoi?a aeuoaoaeueiiai ?eoia (Ae?) e?unyo ia?auo aeiae aeecie. A yenia?eiaioao ia /anoe/ii eciee?iaaiiuo (in situ) eneonnoaaiii noia?ooce?oaiuo iaaeoeeinieiaeueiuo i?aia?aoao (*EINI) e?unyo ia?auo aeiae aeecie iieacaii o/anoea ieneaea acioa (NO) e NMDA-?aoeaioi?ia aicaoaeaeathueo aieiieeneio a ?aaoeyoeee ia?aiao?ia eioaa?e?iaaiiie yeaeo?e/aneie aeuoaoaeueiie aeoeaiinoe a aeeao?aaiaeueiii ia?aa a ii?ia, i?e ae-iienee e i?e nieaeaiee ?I aiaeeaoi/iiai ?anoai?a. NADPH-ae-niaea?aeauea iae?iiu auyaeaiu ai anao ecaanoiuo no?oeoo?ao aei?naeueiie e aaio?aeueiie ?anie?aoi?iuo a?oii iae?iiia i?iaeieaiaaoiai iicaa /aou?aoaeiaaiuo e?unyo, iaeneiaeueiay n?aaeiyy ieioiinoue ia/aiuo iae?iiia iieacaia a ?ino?aeueiie /anoe aaio?ieaoa?aeueiiai ioaeaea i?i-aeieaiaaoiai iicaa (AEIII) - a iaeanoe eaoa?aeueiiai ia?aaeaaioieeaoi/iiai yae?a. N i?eiaiaieai iaoiaea iiia?a/iuo ia?a?acie AEIII e aiieeeaoeee eiieo?aioiiai eiaeaeoi?a NO-neioacu, yeciaaiiuo aeiii?ia NO e noano?aoa aai aeineioaca enneaaeiaaia ?ieue NO a ?aaoeyoeee ia?aiao?ia Ae?, aaia?e?oaiiai *EINI. NO o/anoaoao a iaoaiecia oiie/aneiai oi?iiaeaiey /anoiou Ae?, inouanoaeyaiii ?ino?aeueiie /anoueth AEIII, a oaeaea a oi?ie?iaaiee /anoioii-aiieeooaeiuo oa?aeoa?enoee Ae?, aaia?e?oaiiai no?oeoo?aie, ?aniieiaeaiiuie eaoaeaeueiaa. N i?eiaiaieai iaoiaea iiia?a/iuo ia?a?acie AEIII e aiieeeaoeee iaeiieo?aioiiai aeieaoi?a NMDA-?aoeaioi?ia eaoaieia iieacaii o/anoea aeaiiiai oeia ?aoeaioi?ia a iaoaieciao oiie/aneiai oi?iiaeaiey /anoiou Ae? e oi?iiaeaiey aeeeoaeueiinoe einie?aoeee, inouanoaeyaiuo ?ino?aeueiie /anoueth AEIII iiai?iaeaeaiiuo e?unyo. Auyaeaii, /oi yiaeiaaiiue NO iiin?aaeoao aeeyiea yeciaaiiiai N-iaoee-D-ania?oaoa, aiieeoee?oaiiai ia aaio?aeueioth iiaa?oiinoue i?iaeieaiaaoiai iicaa *EINI, a oi a?aiy eae aiieeeaoeey aeiii?a NO ieo?ii?onneaea iao?ey i?eaiaeeo e eiaeae?iaaieth noeioeyoeee /anoiou Ae? i?e aeaenoaee NMDA. Aeaiiia aeeyiea ieo?ii?onneaea iao?ey naycaii n aeiee?othuei aeaenoaeai ecauoea NO ia NMDA-?aoeaioi?u, oae eae ono?aiyaony aaiiaeiaeiii, naycuaathuei NO. A oneiaeyo aeiiene/aneiai oanoa yiaeiaaiiue NO o/anoaoao a iaoaiecia oaiaoaiey /anoiou Ae? e nio?aiaiee iaiaoiaeeiiai o?iaiy aiieeooaeu e eioaa?aeueiie eioaineaiinoe einie?aoi?iuo ?ac?yaeia, aaia?e?oaiuo *EINI. I?aaeaa?eoaeueiay aiieeeaoeey yeciaaiiiai aeiii?a NO ieo?ii?onneaea iao?ey niinianoaoao ioiineoaeueii iaiueoaio oaiaoaieth /anoiou e oaaee/aieth eioaa?aeueiie eioaineaiinoe einie?aoi?iuo ?ac?yaeia a oneiaeyo aeiiene/aneiai oanoa. Aeiee?iaaiea NMDA-?aoeaioi?ia i?e iineaaeothuae aeiienee i?eaiaeeo e aieaa au?aaeaiiiio oaiaoaieth ia?aiao?ia Ae? *EINI. Yiaeiaaiiue NO iiin?aaeoao noeioeyoeeth /anoiou Ae?, aaia?e?oaiiai *EINI, i?ienoiaeyuoth i?e noia?oocee ?anoai?ii n ?I 7.0. Aeiee?iaaiea NMDA-?aoeaioi?ia i?eaiaeeo e eiaeae?iaaieth noeioeyoeee /anoiou Ae? *EINI i?e aeaenoaee ?anoai?a n ?I 7.0, /oi naeaeaoaeuenoaoao ia o/anoee aeaiiiai oeia ?aoeaioi?ia a iaaeoeey?iie oaii/oanoaeoaeueiinoe aeuoaiey. Eeth/aaua neiaa: NO, NO-neioaca, NMDA, NADPH-aeeaoi?aca, ?I, aeuoaoaeueiue ?eoi, /anoe/ii eciee?iaaiiue iaaeoeeinieiaeueiue i?aia?ao, aaio?ieaoa?aeueiue ioaeae i?iaeieaiaaoiai iicaa, aeiieney. Volgin D.V. Investigation of the medullary regulatory mechanisms of respiratory rhythmogenesis in newborn rats involving nitric oxide and N-methyl-D-aspartate receptors. -Manuscript. Thesis for the candidate's degree by speciality 03.00.13 -physiology of human and animals. - Bogomolets Institute of Physiology of the National Academy of Sciences of Ukraine, Eyiv, 1999. We have studied the NADPH-diaphorase (as a neuronal NO-synthase) reactivity in the medullary structures of respiratory rhytm (RR) generator and the role of NO and NMDA receptors of excitatory aminoacids in the regulation of respiratory activity in the phrenic nerve of the artificial superfused semi-isolated medulla-spinal cord preparations in experiments on newborn rats. NADPH-diaphorase positiveneurons were found in all nuclei of both dorsal and ventral respiratory neuron groups, the maximal density of stained cells was present in the rostral part of ventrolateral medulla (VLM) - in the region of lateral paragigantocellular reticular nucleus. It was found that endogenous NO mediates the mechanism of tonic inhibitory control of the frequency of RR located in the rostral VLM under normal andhypoxic conditions, involved in activation of the frequency of RR by low extracellular pH and in generation of the basic RR by the more caudal structures of VLM. It was shown that NO biosynthesis mediates the effect of NMDA on the RR, but NO can block NMDA receptors. NMDA receptors in the VLM involved in regulation of the parameters of RR under normal, hypoxic and low extracellular ?I conditions. Eey words: NO, NO-synthase, NMDA, NADPH-diaphorase, ?I, respiratory rhythm, semi-isolated medulla-spinal cord preparation, ventrolateral medulla, hypoxia.

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