Angiotensin II and Angiotensin-(1-7) in Paraventricular Nucleus Modulate Cardiac Sympathetic Afferent Reflex in Renovascular Hypertensive Rats.docVIP

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Angiotensin II and Angiotensin-(1-7) in Paraventricular Nucleus Modulate Cardiac Sympathetic Afferent Reflex in Renovascular Hypertensive Rats.doc

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Angiotensin II and Angiotensin-(1-7) in Paraventricular Nucleus Modulate Cardiac Sympathetic Afferent Reflex in Renovascular Hypertensive Rats

AngiotensinIIandAngiotensin-(1-7)inParaventricular NucleusModulateCardiacSympatheticAfferentReflex inRenovascularHypertensiveRats Hai-JianSun,PengLi,Wei-WeiChen,Xiao-QingXiong,YingHan* DepartmentofPhysiology,NanjingMedicalUniversity,Nanjing,Jiangsu,China Abstract Background: The enhanced cardiac sympathetic afferent reflex (CSAR) is involved in the sympathetic activation that contributestothepathogenesisandprogressionofhypertension.ActivationofAT1receptorsbyangiotension(Ang)IIinthe paraventricularnucleus(PVN)augmentstheenhancedCSARandsympatheticoutflowinhypertension.Thepresentstudyis designedtodeterminewhetherAng-(1-7)inPVNplaysthesimilarrolesasAngIIandtheinteractionbetweenAng-(1-7)and AngIIonCSARinrenovascularhypertension. Methodology/PrincipalFindings:Thetwo-kidney,one-clip(2K1C)methodwasusedtoinducerenovascularhypertension. The CSAR was evaluated by the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to epicardialapplicationofcapsaicininsinoaortic-denervatedandcervical-vagotomizedratswithurethaneanda-chloralose anesthesia.EitherAngIIorAng-(1-7)inPVNcausedgreaterincreasesinRSNAandMAP,andenhancementinCSARin2K1C rats than in sham-operated (Sham) rats. Mas receptor antagonist A-779 and AT1 receptor antagonist losartan induced oppositeeffectstoAng-(1-7)orAngIIrespectivelyin2K1Crats,butlosartanhadnoeffectsinShamrats.Losartanbutnot the A-779 abolished the effects of Ang II, while A-779 but not the losartan blocked the effects of Ang-(1-7). PVN pretreatmentwithAng-(1-7)dose-dependentlyaugmentedtheRSNA,MAP,andCSARresponsestotheAngIIin2K1Crats. AngIIlevel,AT1receptorandMasreceptorproteinexpressioninPVNincreasedin2K1CratscomparedwithShamratsbut Ang-(1-7)leveldidnot. Conclusions:Ang-(1-7)inPVNisaseffectiveasAngIIinenhancingtheCSARandincreasingsympatheticoutflowandboth endogenous Ang-(1-7) and Ang II in PVN contribute to the enhanced CSAR and sympathetic outflow in renovascular hypertension.Ang-(1-7)inPVNpotentiatestheeffectsofAngIIinrenov