AT II Receptor Blockade Thiab Renal Denervation: Kev cuam tshuam sib txawv nrog rau kev cuam tshuam rau lub raum?

Hu rau:tina.xiang@wecistanche.com

Abstract

Keeb kwm: Angiotensin Il (Ang Il) thiab covlub raum sympatheticlub paj hlwb exert muaj zog ntawm lub raum sodium thiab dej excretion. Peb tau sim qhov kev xav tias twb tau koob tshuaj tsawg ntawm Ang I inhibitor (candesartan) yuav ua rau muaj kev cuam tshuam zoo sib xws ntawm tubular sodium thiab dej reabsorption hauv congestive heart failure (CHF) raws li pom tom qab lub raum denervation (DNX).

Cov txheej txheem: Kev ntsuas ntshav siab, lub plawv dhia (HR),lub raum sympatheticLub paj hlwb (RSNA), glomerular filtration rate (GFR), lub raum plasma flow (RPF), zis ntim, thiab zis sodium. Txhawm rau ntsuam xyuas neural tswj ntawm ntim homeostasis, 21 hnub tom qab induction ntawm CHF ntawm myocardial infarction nas underwent ntim expansion (0.9 feem pua ​​NaCL; 10 feem pua ​​​​lub cev hnyav) kom txo RSNA. CHF nas thiab tswj nrog lossis tsis muaj DNXor pretreated nrog Ang l hom -1 receptor antagonist candesartan (0.5 ug i..) tau kawm. Cov txiaj ntsig: CHF nas excretedonly68 ntxiv rau 10.2 feem pua ​​​​ntawm cov ntim ntim (10 feem pua ​​​​lub cev hnyav) hauv 90 min. CHF nas

pretreated nrog candesartan lossis tom qab DNX tawm los ntawm 92 mus rau 103 feem pua ​​​​zoo li kev tswj hwm. Kev txo qis ntawm RSNA tshwm sim los ntawm qhov ntim nthuav dav tau cuam tshuam hauv CHF nas tab sis tsis cuam tshuam los ntawm candesartan taw qhia rau kev siv tshuaj intrarenal.GFR thiab RPF tsis txawv txav hauv kev tswj lossis CHF.Conclusion: Lub luag haujlwm tseem ceeb ntawm kev nce RSNA- khaws ntsev thiab dej tsis tuaj yeem ntev dua yuav pom tom qab lub raum Ang ll receptor blockade hauv CHF nas.

Ntsiab lus:Lub raum sympathetic innervation · Angiotensin II · Congestive plawv tsis ua hauj lwm · Lub raum hlab ntsha ablation · Raum muaj nuj nqi

nyem rau cov lus qhia ntxiv txog cistanche khoom rau lub raum

Taw qhia

Nws tau paub txij li thaum xyoo pua 19thlub raum sympatheticinnervation influences ntsev thiab dej excretion ntawm lubraumnce sympathetic paj hlwb ua rau sodium thiab kua retention [1]. Tau ntau xyoo cov kev tshawb fawb soj ntsuam tau pom tias nyob rau hauv cov ntshav siab, lub raum sympathetic paj hlwb (RSNA) tau nce [2, 3].

Me ntsis kev saib xyuas me ntsis tau them rau qhov tseeb tias txawm tias nyob rau hauv qhov tsis zoo ntawm qhov ntim khaws cia, qhov chaw kho mob tseem ceeb tshaj plaws uas yog lub plawv tsis ua haujlwm (CHF), muaj qhov nce siab hauv cov hlab ntsha hauv lub raum|4, 5]. Txawm hais tias cov teebmeem ntawm lub raum paj hlwb ablation hauv arterial hypertension tau kawm ntau lub sijhawm [6-8], nws tsuas yog nyob rau hauv 10 xyoo dhau los uas cov teebmeem ntawm lub raum denervation (DNX) hauv cov neeg mob plawv tsis ua haujlwm tau kawm. [9-12].

Lub raum paj hlwb ablationtau sim hauv cov neeg mob uas muaj CHF nrog qhov zoo[13-16] thiab cov txiaj ntsig tsis zoo [17,18]. Kev tshuaj xyuas thiab kev tshuaj ntsuam xyuas meta ntawm lub raum paj hlwb ablation hauv lub plawv tsis ua haujlwm qhia tias muaj txiaj ntsig zoo ntawm kev cuam tshuam rau cov neeg mob plawv, tab sis tsis muaj kev tshawb fawb loj dua [9-12].

Ntawm qhov tod tes, intrarenal teebmeem ntawm sympathetic innervation (xws li ntawm glomeruli, tubulin, thiab juxtaglomerular apparatus) kuj tuaj yeem cuam tshuam los ntawm kev siv tshuaj, tshwj xeeb yog kev tswj hwm ntawm sympatholytics, 1 sympatholytics, thiab inhibitors ntawm renin-angiotensin system [3] ]. Tshwj xeeb tshaj yog hais txog cov teebmeem intrarenal ntawm angiotensin II (Ang II), peb muaj peev xwm qhia tau nyob rau hauv cov kev tshawb fawb yav dhau los uas tsis tshua muaj cov tshuaj inhibitor ntawm Ang II receptors ua rau txhim kho normalized sodium thiab dej excretion tsis cuam tshuam los ntawm kev mob hnyav thiab mob ntev ntawm RSNA. [19, 20].

Hauv cov kev sim no, ntsev thiab dej tso tawm, nrog rau glomerular filtration rate (GFR) thiab lub raum plasma flow (RPF), tau ntsuas kom raug ntsuas cov txiaj ntsig ntawm cov paj hlwb ntawm lub raum los ntawm kev ua haujlwm tsis zoo. Yog li, peb tau sim qhov kev xav tias qhov koob tshuaj tsawg ntawm Ang II inhibitor (candesartan) yuav ua rau muaj kev cuam tshuam zoo sib xws ntawm tubular sodium thiab dej reabsorption hauv CHF raws li pom tom qab DNX.

Khoom siv thiab cov txheej txheem

Kev Npaj Tsiaj Tsiaj thiab Cov Txheej Txheem Kev Ua Haujlwm

Txiv neej Sprague-Dawley nas, 250-300 g lub cev hnyav (Charles Riv-er Wiga, Sulzfeld, Lub teb chaws Yelemees) tau khaws cia rau hauv ib chav ntawm 24 ± 2 degree nrog nrog 60-80 feem pua ​​​​cov av noo thiab noj cov zaub mov uas muaj 0.2 feem pua ​​​​sodium nrog dawb nkag mus rau kais dej. Cov txheej txheem tau ua raws li National Institutes of Health Guide for the Care and Use of Labor-tory Tsiaj thiab tau pom zoo los ntawm tsoomfwv cov koomhaum (Mittelfranken, Ansbach thiab Unterfranken, Würzburg, Lub Tebchaws Yelemees).

Kev sim CHF

Raws li yav dhau los tau piav qhia [21] ligation ntawm intraventricular coronary artery tau siv los tsim CHF ntev. Cov nas tsuag tau muab tshuaj loog nrog methohexital sodium (50 mg / kg ip): tom qab lub tshuab cua tshuab nrog cua tau pib, lub plawv tau nkag mus rau hauv nruab nrab thoracotomy, cov hlab ntsha intraventricular coronary tau ligated thiab lub thorax kaw. Tag nrho cov kev tshawb fawb tom qab tau pib tsis pub dhau 3 lub lis piam tom qab coronary artery ligation. SHAM-kho nas yeej ib txwm npaj ua ke.

Lub raum Denervation

Ob lub lis piam tom qab coronary artery ligature, pab pawg nas nrog CHF los yog tswj tau ob tog denervated los yog underwent sham ua hauj lwm. Tom qab ob tog flank incisions, DNX tau pib los ntawm kev phais tshem tawm lub raum cov hlab ntsha thiab cov leeg ntawm adventitia, txiav tag nrho.lub raumCov paj hlwb nyob rau hauv lub tshuab kuaj kab mob dissection (25 ×), thiab kho cov hlab ntsha nrog kev daws ntawm 10 feem pua ​​​​phenol hauv 95 feem pua ​​​​ethanol [19].

Kev sim teeb tsa

Peb lub lis piam tom qab coronary artery ligature, nyob rau hauv anesthetized nas polyethylene catheters tau muab tso rau hauv cov hlab ntsha los yog venous femoral hlab ntsha thiab ntxiv polyethylene tubing rau hauv lub zais zis rau sau zis [19]. Cov ntaub ntawv kaw tseg ntawm sab xis RSNA tau ua tiav raws li tau piav qhia yav dhau los hauv nas yam tsis muaj DNX[22-24]. Los ntawm txoj kev mus rau sab nraud, lub raum paj hlwb raug muab tshem tawm los ntawm cov ntaub so ntswg sib txuas thiab muab tso rau ntawm lub tshuab hluav taws xob bipolar. Cov paj hlwb tau hloov kho tag nrho cov nthwv dej thiab sib xyaw ua ke dhau ntawm 1-s ntu nrog cov ntaub ntawv muag khoom thiab tshuaj xyuas software (SciWorks 7.2, Da-taWave Technologies, Loveland, CO, Loveland, CO, USA).

Kev soj ntsuam ntawm koob tshuaj ntawm ANGIIATI-Receptor Antagonist Candesartan

Hauv ib pab pawg sib txawv ntawm cov nas ib txwm Sprague-Dawley, 3 koob tshuaj ntawm Ang II receptor antagonist candesartan (0.5,1.5, thiab 3ug iv) tau txhaj tshuaj los tiv thaiv cov teebmeem ntawm Ang II [25]. Txhawm rau kuaj xyuas qhov thaiv ntawm qhov systemic Ang II AT receptors, peb muab 20ng ntawm ANG II intravenously 10 min ua ntej thiab 10 min tom qab txhaj tshuaj candesartan. Cov koob tshuaj qis tshaj plaws ntawm candesartan thaiv cov lus teb hemodynamic thiab tau siv hauv cov kev tshawb fawb tom ntej.

Lub raumCov lus teb rau 10 min lub sij hawm ntawm compressor infusion ntawm Ang II (13ng / min) ntawm cov zis ntim (UV) thiab urinary sodium excretion (UwaV) tau kawm. Physiological saline tau infused intravenously ntawm tus nqi ntawm 60 uL / ​​min kom txog thaum lub xeev khov kho (saline input=zis zis). Tom qab ntawd, tom qab 3 lub sijhawm tswj hwm, cov tshuaj compressor ntawm Ang II tau muab ntxiv rau hauv qhov dej rau 10 feeb, tom qab ntawd los ntawm lwm lub sijhawm 2 10min rov ua haujlwm yam tsis muaj Ang I. Ib pawg nas tau pretreated nrog saline, lwm tus tau txais 0.5ugi .v. ntawm AT1-receptor antagonist candesartan (bolus txhaj ntawm 30 μL ntim).UV thiab UNAV hauv cov pab pawg no tau raug soj ntsuam.

Volume Expansion after Low-Dose ANGII Receptor Blockade (0.5 ug Candesartan)

Sai li qhov kev npaj phais tas lawm, cov zis tau sau ntau dua 15 feeb lossis 30 feeb. Physiological saline tau tswj hwm ntawm tus nqi ntawm 60 uL / ​​min rau tag nrho lub sijhawm ntawm kev sim. Inulin thiab PAH tshem tawm tau txiav txim siab raws li tau piav qhia yav dhau los [19].

Tom qab tau ua tiav "kev nyob ruaj khov," Ang I AT1- receptor antagonist candesartan (0.5ug iv) lossis tsheb (0.9 feem pua ​​NaCl) tau txhaj tshuaj raws li bolus ( 30μL ntim iv). Tom qab 215 feeb tswj lub sijhawm, txhua tus nas tau txais kev sib tw ntim nrog ntsev rau 30 feeb (10 feem pua ​​​​ntawm lub cev hnyav). Tom qab ntawd, muaj 3 lub sijhawm ntxiv ntawm 30 feeb kom rov zoo. Cov ntshav kuaj ntawm 150 L tau sau nyob rau nruab nrab ntawm txhua lub sijhawm rau kev soj ntsuam ntawm GFR thiab RPF. Thaum kawg ntawm qhov kev sim, ib lub catheter tau muab tso rau ntawm txoj cai carotid hlab ntsha mus rau sab laug ventricle thiab tau siv los ntsuas sab laug-ventricular kawg-diastolic siab [21] muab kev ntsuam xyuas ncaj qha ntawm myocardial contractility piv rau echocardiographic txoj kev [26 ]. Thaum kawg, 3 mg ntawm ganglionic blocking tus neeg saib xyuas trimetapham-camsylate (Hoffmann-La Roche, Basel, Switzerland) tau tswj hwm los inhibit postsynaptic RSNA. Cov haujlwm keeb kwm yav dhau los uas tseem muaj tam sim no raug rho tawm los ntawm cov haujlwm uas tau sau tseg thoob plaws qhov kev sim. Ib daim ntawv qhia txog kev sim loj ntawm qhov project yog nthuav tawm hauv daim duab 1.

Kev kuaj zis

Cov zis ntim tau ntsuas gravimetrically. Cov zis thiab ntshav plasma sodium concentrations tau soj ntsuam los ntawm nplaim taws photometry, Qhov tseem ceeb rau cov zis ntim tau qhia ib gram lub cev qhov hnyav. Cov zis thiab ntshav plasma inulin thiab PAH concentrations tau txiav txim los ntawm anthrone thiab ethylenediamine txoj kev los ntsuam xyuas inulin thiab PAHclearances [19].

Kev txheeb cais

Integrated RSNA raug kaw ua μV × s. Lub hauv paus tseem ceeb ntawm RSNA (UV × s), ntsuas ntshav siab (mm Hg), thiab lub plawv dhia (bpm) tau txheeb xyuas siv ib txoj kev ANO-VA nrog Dunnett's post hoc test. Statistical tseem ceeb tau txhais raws li p<0.05. data="" are="" given="" as="" group="" means±se="" in="" the="" results="" section="" or="" tables="" and="" displayed="" in="" the="" figures="" as="" box="" and="" whiskers="" plots.="" sigmastat="" 3.5(systat="" software)="" was="" used="" for="" statistical="">

Cov txiaj ntsig

20 ng ntawm Ang II tau txhaj tshuaj hauv 10 feeb ua ntej thiab 10 feeb tom qab kev tswj hwm ntawm candesartan. Cov txiaj ntsig tau pom nyob rau hauv daim duab 2. Cov koob tshuaj ntau dua tau thaiv cov lus teb rau cov exogenous Ang II loj heev los ntawm - 69 ± 7 feem pua ​​(1.5 ugs) thiab 82 ± 5 feem pua ​​(3 ugs), feem. Qhov koob tshuaj qis tshaj n (0.5 ug) tsis cuam tshuam rau lub tshuab luam ntawv

Qhov nruab nrab lub cev hnyav ntawm cov tsiaj lub plawv tsis ua hauj lwm thiab kev tswj tau qhia meej nyob rau hauv Table 1. Ntawm kev ceeb toom, lub cev nyhav ntawm cov nas plawv tsis ua hauj lwm thiab kev tswj tsis sib txawv. Yog li ntawd, qhov ntim tseem ceeb hauv cov nas no qhia tau hais tias lub xeev mob hnyav tseem tsis tau tshwm sim ntawm nws lub sijhawm.

Lub plawv qhov hnyav / lub cev hnyav piv tau ntau dua hauv CHF nas dua li hauv kev tswj hwm ({{0}}.49±0.07 feem pua ​​​​hauv CHF vs.0.35±0.08 hauv tswj). Sab laug ventricular kawg-diastolic siab tau nce siab hauv cov nas plawv tsis ua haujlwm (18.9 ± 8.1 mm Hg) piv rau cov tsiaj tswj (2.9 ± 1.2 mm Hg). Ob qhov kev txwv tsis pub dhau CHFin peb cov tsiaj sim.

teb rau exogenous Ang II. Txawm li cas los xij, qhov koob tshuaj qis tshaj plaws ntawm AT {{0}} receptor inhibitor tau ua pov thawj tias tseem muaj txiaj ntsig zoo ntawm lub raum AT1 receptors, txij li cov dej thiab sodium retention uas tau tshwm sim los ntawm compressor koob tshuaj Ang II (13 ng / min. ), tuaj yeem cuam tshuam tom qab kev kho mob nrog 0.5 ug candesartan (Fig. 3).

los ntawm 92 mus rau 103 feem pua ​​​​uas yog qhov loj dua qhov kev tso tawm ntawm cov tsiaj tsis kho plawv. Raws li pom nyob rau hauv Table 2 urinary flow rate (UV) thiab urinary Na excretion (UNA V) nce thiab mus txog qib siab tshaj plaws thaum lub sij hawm ntim nthuav dav thiab rov qab los tswj qhov tseem ceeb hauv peb 30 lub sij hawm rov qab los. Cov qauv no zoo ib yam rau tag nrho 6 pawg tsiaj uas tsis muaj qhov sib txawv ntawm lawv. Tsiaj txhu nrog coronary artery ligature, txawm li cas los xij, tau nthuav tawm qhov nce me me ntawm UV thiab UNAV piv rau qhov muaj kev tswj hwm thiab cov tsiaj ua ntej nrog AT1 inhibitor lossis DNX.

Qhov kev hloov pauv ntawm RSNA hauv cov nas nrog cov hlab ntsha ntawm cov hlab ntsha thiab tswj cov tsiaj thaum lub sij hawm nthuav dav thiab rov qab los tau tshwm sim hauv daim duab 5, raws li. Basal absolute RSNA theem yog 500 ± 39μV rau cov pab pawg neeg lub plawv tsis ua hauj lwm thiab rau kev tswj 370 ± 34 μV.In nas nrog coronary-artery ligature, qhov siab tshaj plaws txo nyob rau hauv RSNA tshwm sim tom qab 20 min thiab nyob rau hauv cov tsiaj tswj 15 min tom qab qhov pib ntawm ntim expansion . Tsis muaj qhov sib txawv tseem ceeb hauv kev nyuaj siab tshaj plaws ntawm RSNA. Hauv thawj 30 feeb tom qab txiav tawm ntawm qhov ntim nthuav dav, RSNA rov qab los tswj cov txiaj ntsig hauv cov nas nrog cov hlab ntsha ntawm cov hlab ntsha thiab tseem nyob ntawd rau lub sijhawm rov qab los. Hauv kev tswj cov tsiaj, txawm li cas los xij, RSNA tseem muaj kev nyuaj siab.RSNA muaj qhov sib txawv ntawm cov nas uas muaj kab mob plawv thiab tswj tsiaj rau tag nrho 1.5 teev rov qab lub sijhawm. Cov qauv no tsis cuam tshuam los ntawm kev kho mob nrog Ang I AT1 inhibitor candesartan.

Nyob rau hauv tsis muaj ib pawg ntawm kev sim cov ntshav siab, lub plawv dhia, GFR, lossis RPF tau cuam tshuam los ntawm cov txheej txheem sim. Cov ntaub ntawv rau GFR thiab RPF tau tshwm sim hauv daim duab-ure6a, b. Cov ntaub ntawv qhia txog ntshav siab thiab lub plawv dhia tau muab rau hauv Table 3.

Kev sib tham

Peb cov ntaub ntawv qhia tias cov teebmeem ntawm tubular ntawm kev ua kom lub paj hlwb muaj zog (sodium thiab dej reabsorption) tuaj yeem cuam tshuam nrog qis qis ntawm Ang II receptor inhibitors. Qhov kev tshawb pom no tuaj yeem yog qhov tseem ceeb hauv kev kho mob vim tias muaj kev cuam tshuam ntawm ntsev thiab dej tuav yog qhov tseem ceeb hauv sodium retaining disorders xws li CHF.

Muaj ob peb lub tswv yim uas RSNA thiab Ang II cuam tshuam rau lub raum sodium thiab dej tuav ua rau muaj kev cuam tshuam zoo sib xws ntawm sodium thiab dej tawm hauv cov xwm txheej ntawm RSNA nce: piv txwv li, kev ua siab zoo paj hlwb txhawb lub juxtaglomerular apparatus ntxiv rau nws cov teebmeem tubular kom ib paj hlwb-dependent renin secretion yuav tshwm sim [27]. Intrarenal teebmeem ntawm Ang II ntawm ntsev thiab dej tso tawm, tshwj xeeb tshaj yog nyob rau ntawm qhov chaw luminal ntawm tubule28] tuaj yeem cuam tshuam sodium reabsorption nyob rau hauv-nyob ntawm RSNA uas paub tias cuam tshuam nrog sodium reabsorption ntawm cov chaw no [3].

Ntawm qhov tod tes, peb cov txiaj ntsig tuaj yeem pom tau tias yog kev txhawb nqa kev pom hauv cov ntaub ntawv hais tias qhov cuam tshuam ntawm tubular ntawm kev ua kom lub paj hlwb muaj zog (sodium thiab dej reabsorption) tej zaum yog nyob ntawm lub raum Ang II [29-31].

Txawm hais tias cov txheej txheem koom nrog, cov lus nug tseem ceeb yog seb lub raum puas siab puas ntsws denervation-ib txheej txheem rhuav tshem lub cev tswj lub cev- tuaj yeem muab cov txiaj ntsig tseem ceeb hauv cov neeg mob nrog CHF (nrog thiab tsis muaj ntshav siab) ntxiv rau kev kho tshuaj nrog, piv txwv li, Ang I inhibiting. kev kho mob.

Lub raum paj hlwb ablation lub cev rhuav tshem ib feem ntawm cov hlab plawv lub paj hlwb. Tab sis cov hlab ntsha no regrow thiab me ntsis paub txog cov teebmeem tom qab ntawm lub raum ua haujlwm [32], uas ua rau qhov teeb meem nyuaj.

Tsis tas li ntawd, muaj cov lus qhia hais tias kev sib haum xeeb innervation ntawm tusraumtej zaum yuav pab tswj kom perfusion ntawm ob lub raum thaum muaj ntshav poob [24, 33,34]. Qhov no tuaj yeem yog lub ntsiab lus los txiav txim siab rau cov neeg laus cov neeg mob plawv vim tias ntau thiab ntau tus neeg laus tau raug phais [35].

NHE3 (Na plus / H plus exchanger 3) yog qhov tseem ceeb tshaj plaws Nat transporter nyob rau hauv lub proximal tubules ntawm lub raum [36] thiab yog txuas rau Ang II thiab muaj feem xyuam rau hypertensive mob. Hauv vitro, nanomolar concentrations ntawm Ang Il nce NHE3 kev qhia hauv kab lis kev cai nyob ze ntawm tubule hlwb [37,38].In vivo, cov tshuaj qis qis ntawm Ang I kuj tau nce qhov kev qhia ntawm NHE3, nrog rau qhov sib thooj Nat reabsorption [39]. Tsis ntev los no, kev sib raug zoo ncaj qha ntawm Ang II thiab NHE3 nyob rau hauv qhov sib thooj tu-blues ntawm lub raum nrog cov lus teb tsis zoo-natriuresis tau tshaj tawm [40].

Tsis tas li ntawd, qhov stimulation ntawm sodium reabsorption nyob rau hauv cov ducts sau tau hais tias muaj zog cuam tshuam los ntawm Ang II hom 1-receptor activation ntawm epithelial Na channels thiab ntxiv distal transporters[41-43]. Li no, Ang I cuam tshuam rau sodium reabsorption tsawg kawg hauv tib lub tubular ntu li RSNA.

Txawm hais tias muaj kev txhaj tshuaj tsawg tsawg ntawm Ang II, peb tau yooj yim pom muaj sodium thiab dej tuav hauv peb qhov kev sim. Txij li thaum tsuas yog lub excretion ntawm ib tug luv luv saline infusion raug soj ntsuam raws li ib tug "classical" functional test ntawm lub raum sympathetic inhibition tiav, sib txawv kev sim pab pawg nyob rau hauv heev zoo sib xws tej yam kev mob yuav muab piv. Tshwj xeeb, hauv cov tsiaj uas muaj myocardial infarction, lub raum ntshav ntws, thiab GFR tsis txawv ntawm ntau pawg CHF thiab tswj cov nas. Tsis tas li ntawd, peb tau pom tias qhov kev tswj xyuas mob hnyav ntawm Ang I inhibitor tsis cuam tshuam RSNA hauv ib qho ntawm cov pab pawg tshawb xyuas. Qhov kev soj ntsuam no qhia tau hais tias candesartan tsis cuam tshuam rau lub hauv paus ntawm kev ua siab zoo paj hlwb. Txawm li cas los xij, candesartan tuaj yeem ua rau muaj kev cuam tshuam ntawm Ang I thiab cov paj hlwb uas muaj kev sib haum xeeb nyob ze ntawm lub cev. RSNA raug kaw ua ntej cov paj hlwb nkag mus rau hauv lub raum thiab taug kev mus rau hauv lub cev. Txawm li cas los xij, kev tswj hwm ntev ntawm cov tshuaj inhibiting qhov cuam tshuam ntawm Ang II tuaj yeem ua rau txo qis ntawm lub hauv paus sympathetic outflow. Qhov no tau tshwm sim los ntawm cov hlab ntsha ncaj qha kaw [2]. Qhov chaw ntawm qhov kev txiav txim ntawm qhov kev txo qis ntawm cov hlab ntsha ntawm lub paj hlwb tuaj yeem yog thaj tsam postrema uas muaj qhov siab ntawm Ang IIreceptors [44], qhov twg cov ntshav-hlwb tsis txaus tso cai rau cov tshuaj los ntawm cov kab mob hauv lub cev mus rau hauv nruab nrab. neurons [45].

Endogenous Ang II tuaj yeem hloov kho cov hlab ntsha-mediated antinatriuresis thiab antidiuresis los ntawm kev ua ua ntej lossis postsynaptic ntawm qib tubular: presynaptic yooj yim ntawm transmitter tso tawm los ntawm sympathetic varicosities los ntawm Ang II tau pom [46]. Ang II kuj tseem tuaj yeem pom muaj kev sib koom ua ke postsynaptic nrog tso tawm norepinephrine [47]: hauv daim ntawv tshaj tawm no, cov txiaj ntsig tau nthuav tawm qhia tias cov lus teb neurally mediated tubular yuav tsum tau qis qis ntawm Ang I txij li thaum kev tsim cov peptide yog inhibited, lub raum hlab ntsha- induced antinatriuresis thiab antidiuresis raug tshem tawm tab sis yuav pom dua thaum lub sij hawm infusion ntawm Ang II. Nws tau sib cav ntxiv tias Ang I exerts nws qhov kev txiav txim ntawm lub raum paj hlwb junctions ntawm lub epithelial hlwb ntawm lub raum tubule. Hauv lwm cov lus ceeb toom, intrarenal Ang II tau pab txhawb alpha-adrenoceptor-mediated sodium reabsorption hauv kev teb rau kev ntxhov siab ntawm post- thiab presynaptic Ang II receptors [48]. Li no, Ang Il tuaj yeem muaj qhov tseem ceeb rau cov teebmeem ntawm cov hlab ntsha ntawm lub raum paj hlwb kev ua haujlwm ntawm cov ntsev thiab dej tawm nrog kev nce ntxiv hauv RSNA [19] nrog rau kev ua haujlwm ntev nce hauv daim siab cirrhosis [20] thiab CHF.

Hauv cov qauv tsiaj, DNX-vim qee qhov kev txhim kho hauv cov pab pawg hauv plawv tsis ua haujlwm uas pom tau tias muaj kev sib koom siab ntau ntxiv rau cov paj hlwb 49]. Cov lus ceeb toom ntawm lub raum paj hlwb ablation nyob rau hauv cov neeg mob uas raug kev txom nyem los ntawm CHF tsis tau pom ib txwm muaj txiaj ntsig zoo [17, 18]. Nyob rau hauv ib txoj kev tshawb nrhiav ib leeg-caj npab feasibility uas siv lub raum hlab ntsha ablation nyob rau hauv cov neeg mob uas muaj systolic plawv tsis ua hauj lwm thiab lub raum tsis ua hauj lwm, txo qhov tseem ceeb ntawm NT-proBNP tab sis tsis muaj ntxiv kev txhim kho nyob rau hauv lub plawv los yog lub raum ua hauj lwm yuav ua tau pom [14]. Ntawm qhov tod tes, ib txoj kev tshawb fawb siv 60 cov neeg mob uas raug kev txom nyem los ntawm CHF nrog txo qis ejection feem qhia txog kev txhim kho ntawm lub plawv ua haujlwm raws li kev soj ntsuam los ntawm NYHA kev faib tawm tom qab lub raum paj hlwb ablation ac-ua ke los ntawm kev nce 6 min taug kev deb thiab muaj kev hloov pauv hauv NT proBNP. [13]. Tsis tas li ntawd nyob rau hauv ib qho chaw, yav tom ntej, randomized, thiab tswj kev kawm, lub raum paj hlwb ablation nyob rau hauv 60 cov neeg mob uas muaj mob systolic lub plawv tsis ua hauj lwm txhim kho lub plawv muaj nuj nqi nrog rau kev ua siab ntev [16]. Thaum kawg, hauv qhov ua tau me me, kev tshawb fawb ntawm lub raum paj hlwb ablation tau pom muaj txiaj ntsig rau cov neeg mob hauv lub plawv tsis ua haujlwm thaum ntxov [15].

Nyob rau hauv tsis muaj ib qho ntawm cov kev tshawb fawb no puas tau tsim txoj kev tshawb fawb nruj tswj cov tshuaj sib xyaw ua ke uas cov neeg mob tau siv. Yog li, qhov cuam tshuam ntawm Ang II inhibition ntawm tubular sodium thiab dej reabsorption lossis inhibitory cuam tshuam ntawm beta-adrenoceptor inhibitors ntawm juxtaglomerular apparatus uas tso tawm renin raws li hauv-creased sympathetic paj hlwb kev ua haujlwm [50] tsis tuaj yeem tham kom tsim nyog hauv cov ntsiab lus ntawm CHF. .

Afferent paj hlwb muaj nyob rau hauv thiab taug kev los ntawm ob lub raum mus rau hauv nruab nrab paj hlwb [51]. So kom txaus afferent lub raum paj hlwb tau tshaj tawm tias yuav nce hauv nas nrog CHF. Qhov kev tshawb pom no tau raug txhais raws li qhia tias hauv CHF hloov lub raum afferent paj hlwb tuaj yeem ua lub luag haujlwm rau kev pom zoo hauv nruab nrab sympathetic outflow [51]. Cov txheej txheem yuav cuam tshuam txog kev hloov pauv nitric oxide ntau lawm hauv hypothalamic paraventricular nucleus txij li lub raum afferent denervation tau pom los tiv thaiv qhov txo qis ntawm neuronal nitric oxide nyob rau hauv paraventricular nucleus hauv cov nas plawv tsis ua haujlwm uas ua rau txo qis ntawm kev ua siab zoo [51].

Hauv cov tsiaj ua qauv ntawm kev kub siab, kev ua kom lub raum tsis zoo ntawm lub raum ntawm dorsal rhizotomy tau pom tias txo cov ntshav siab [52]. Cov txiaj ntsig no qhia tias lub luag haujlwm tseem ceeb ntawm kev ua haujlwm rau lub raum paj hlwb yuav ua rau muaj kev cuam tshuam hauv nruab nrab ntawm kev sib haum xeeb. Txij li thaum los ntawm ib sab ntawm efferent sympathetic innervation ntawm lub raum yog pom tseeb kuj yog ib tug afferent paj mov los ntawm lub raum, uas kom deb li deb to taub tsis zoo cuam tshuam rau tiam ntawm sympathetic kev ua ub no, muaj yog obviously tsis tau tsuas yog ib tug yog vim li cas yuav qhia rau lub raum hlab ntsha ablation nyob rau hauv lub cev. dab tsi kab mob ua tib zoo.

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