Stroke

stroke.ahajournals.org
Stroke.201445:AWP212
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InternationalStrokeConferencePosterAbstracts
SessionTitle:ExperimentalMechanismsand
ModelsPostersI
AbstractWP212:CombinationTherapyWithAmlodipineand
IrbesartanPersistsaNeuroprotectiveEffectAssociatedWithGlial
DeactivationonParaventricularNucleusinHypertensiveRats
YuHasegawaTakashiNakagawaKenUekawaMinglieMaHakubunLin
HiroyukiKusakaTetsujiKatayamaDaisukeSuetaKensukeToyama
NobutakaKoibuchiShokeiKimMitsuyama
+

AuthorAffiliations

Abstract
Although combination therapy with calcium channel antagonist and angiotensin II receptor
blockerissometimesmoreeffectiveforhypertensionthanmonotherapy,itislittleknownthe
significant roles against stroke onset. In this study, we investigated the beneficial effect of
thecombinationtherapywithamlodipineandirbesartanagainststrokeonsetinstrokeprone
spontaneously hypertensive rats (SHRSP). Highsaltloaded SHRSP were assigned to
1)vehicle, 2)amlodipine (AM 2mg/kg/day), 3)irbesartan (IR 20mg/kg/day), and 4)AM+IR.
The drugs were given every day until 35 days. Incidences of neurological deficit and
mortalitywere monitored every day and blood pressure was measured at 7 and 28 days.
Cerebralbloodflow(CBF),weightofbrainandleftventricle(LV)andhistologicalevaluations
wereconductedat42days.ThebloodpressureinAMandAM+IRgroupsweresignificantly
reducedcomparedwiththatinvehiclegroups.Althoughtheincidenceofneurologicaldeficit
andmortalityuntil28dayswere90%and40%invehiclegroup,theratsintreatmentgroups
were almost healthy until 35 days. After the drugs discontinued, abnormal signs were
frequentlyseeninmonotherapygroupsuntil42days(neurologicaldeficitAM50%,IR50%,
AM+IR 0%, mortality AM 30%, IR 10%, AM+IR 0%). Although there was no significant
difference in CBF among the groups, the weight of brain and LV in AM+IR group were
decreasedcomparedwiththoseinsingletreatmentgroups.
Histological findings showed that glial activation at paraventricular nucleus and atrophy of
whitematterweremoreseeninstrokegroupcomparedwithnonstrokegroups.Thesedata
suggestthatthetherapywithAM+IRpersistaneuroprotectiveeffectagainsthypertension
inducedstrokeonsetandtheeffectmightassociatewithglialdeactivationonparaventricular
nucleus.
KeyWords:
Stroke
Antihypertensiveagents
Calciumchannelblockers
AngiotensinII

AuthorDisclosures:Y.Hasegawa:None.T.Nakagawa:None.K.Uekawa:None.
M. Ma: None. H. Lin: None. H. Kusaka: None. T. Katayama: None. D. Sueta:
None.K.Toyama:None.N.Koibuchi:None.S.KimMitsuyama:None.
2014byAmericanHeartAssociation,Inc.