Dab tsi yog Cov txiaj ntsig zoo ntawm Nitric Oxide ntawm lub raum
Mar 14, 2022
Yog xav paub ntxiv:ali.ma@wecistanche.com
Ntu Ⅲ: Nitric oxide signaling nyob rau hauv lub raum tswj thiab cardiometabolic noj qab haus huv
Mattias Carlström
NYEM QHOV NO RAUⅠ & Ⅱ
Abstract
Feem ntau ntawm cov kab mob plawv thiab cov kab mob metabolic ua ke nrograumkev ua haujlwm tsis zooyog nce thoob ntiaj teb. Qhov triad ntawm kev tsis sib haum xeeb no cuam tshuam nrog kev mob hnyav thiab kev tuag nrog rau kev lag luam loj heev. Kev nkag siab ntxiv ntawm cov txheej txheem pathophysiological yog qhov tseem ceeb los tsim cov kev tiv thaiv tshiab los yog kev kho mob. Ntawm cov tswv yim mechanisms, compromisednitric oxide(NO) bioactivity txuam nrog oxidative kev nyuaj siab yog suav tias yog ib qho tseem ceeb. TSIS MUAJ (nitric oxide) yog ib tug luv luv-lived diatomic signaling molecule uas exerts heev heev ntawm covlub raum, lub plawv thiab vasculature nrog rau peripheral metabolically active lub cev. Qhov enzymatic L-arginine-dependent NO (nitric oxide) synthase (NOS) txoj hauv kev yog classical saib raws li lub ntsiab ntawm endogenous NO (nitric oxide) tsim. Txawm li cas los xij, kev ua haujlwm ntawm NOS (nitric oxide synthase)Qhov system feem ntau cuam tshuam hauv ntau yam pathologies suav nrograum, kab mob plawv thiab metabolic. Lwm txoj hauv kev, nitrate-nitrite-NO (nitric oxide) txoj kev, ua rau endogenous los yog kev noj haus-derived inorganic nitrate thiab nitrite yuav tsum recycled ntawm serial txo kom tsim bioactive nitrogen hom, suav nrog TSIS (nitric oxide), ywj siab ntawm NOS (nitric oxide synthase)qhov system. Kev taw qhia los ntawm cov hom nitrogen no txuas nrog cGMP-dependent thiab ywj siab mechanisms. Novel txoj hauv kev los kho NO (nitric oxidehomeostasis thaum lub sij hawm NOS (nitric oxide synthase) deficiency thiab oxidative kev nyuaj siab muaj peev xwm kho cov kev siv nyob rau hauv lubraum, mob plawv thiab metabolic.
Nyem rau Cistanche tubulosa hmoov rau mob raum
Cov teebmeem hauv plawv.
Cov kev tshawb fawb tseem ceeb tau tsom mus rau cov kev cuam tshuam ntawm cov hlab plawv ntawm inorganic nitrate supplementation, nrog rau cov teebmeem ntawm cov ntshav siab, endothelial muaj nuj nqi, thiab cov hlab ntsha. Hauv 2006, thawj txoj kev tshawb fawb qhia txog kev txo cov ntshav siab ntawm nitrate supplementation hauv cov neeg laus noj qab haus huv tau pom tias 0.1 mmol / kg ib hnub ntawm sodium nitrate txo qis diastolic ntshav siab los ntawm txhais tau tias. yuav luag 4mmHg (REF.15). Ib txoj kev tshawb fawb tom qab uas tau siv li ntawm peb npaug ntau dua ntawm kev noj zaub mov nitrate, hauv daim ntawv ntawm cov kua txiv beetroot, tau pom tias muaj cov nyhuv txo qis hauv cov ntshav siab (piv txwv li txo qis hauv cov ntshav siab ntawm 10.4mmHg thiab diastolic ntshav siab ntawm 8mmHg), ua ke nrog vasoprotective thiab antiplatelet zog ntawm nitrate. Ntau pab pawg tshawb fawb txij li thaum tau lees paub cov ntshav siab txo qis ntawm nitrate hauv cov tib neeg noj qab haus huv. Hauv ob qhov kev tshuaj ntsuam meta ntawm cov kev tshawb fawb no, systolic ntshav siab tau txo los ntawm 4.1-4.8mmHg thiab diastolic ntshav siab tau txo los ntawm 1.7-2.0 mmHg (REFsi5,15) . Ib qho ntawm cov kev tshuaj ntsuam meta no kuj tau txheeb xyuas cov txiaj ntsig ntawm nitrate kom tsawg ntawm lwm cov kab mob plawv thiab qhia txog kev txhim kho endothelial muaj nuj nqi, txo cov hlab ntsha, thiab txo platelet aggregation nrog qhov kev cuam tshuam no15.
Ntau cov kev tshawb fawb sim siv ntau yam kab mob plawv-vascular qauv, uas feem ntau cuam tshuam nrograumthiab metabolic dysfunction, kuj tau pom cov txiaj ntsig zoo ntawm cov hlab plawv tom qab kev kho mob nrog inorganic nitrate, nrog rau cov nyhuv antihypertensive thiab txhim kho endothelial function8.1s157. Cov txheej txheem hauv qab uas ua rau muaj kev cuam tshuam nrog ntau lub hauv nruab nrog cev thiab kev hloov kho ntawm RAAS, inhibition ntawm arginase, kho eNOS. (nitric oxide synthase)muaj nuj nqi, dampening ntawm sympathetic hyperactivity, thiab anti-inflammatory thiab anti-oxidative teebmeem.
Ib txoj kev tshawb fawb hauv 15 cov neeg mob ntshav siab tau pom tias kev noj zaub mov zoo nitrate tau txhim kho endothelial muaj nuj nqi thiab txo qis systolic thiab diastolic ntshav siab. Qhov siab tshaj plaws ntshav siab-txo cov nyhuv tau pom kwv yees li ntawm 3-4h tom qab noj nitrate thaum cov ntshav plasma nitrite nce siab, thiab cov nyhuv kav ntev li 24 teev. Thawj ob qhov kev tshawb fawb tshawb fawb txog kev mob plawv ntawm cov tshuaj nitrate ntev ntev hauv cov neeg mob ntshav siab tau ua los ntawm ib leeg hauv 2015 thiab tsim cov txiaj ntsig tsis sib haum59160. Ib txoj kev tshawb fawb pom tias TSIS MUAJ (nitric oxide) txo qis hauv ntshav siab tom qab 1 lub lis piam ntawm nitrate supplementation, qhov uas lwm tus tau pom tias cov ntshav siab txo qis tom qab noj cov nitrate txhua hnub piv nrog cov placebo thaum lub sijhawm 4-lub lim tiam, tsis muaj cov tsos mob ntawm tachyphylaxisi{{2} }. Ib txoj kev tshawb fawb 2020 qhia tau hais tias kev noj nitrate txhua hnub rau 5 lub lis piam, nyob rau hauv daim ntawv ntawm cov nplooj ntsuab ntsuab los yog tshuaj nitrate, tsis tau txo cov ntshav siab hauv cov neeg laus uas muaj ntshav siab ua ntej lossis theem. 1 mob ntshav siab piv nrog rau kev noj zaub mov tsis txaus-nitrate I6. Cov kev tshawb pom sib txawv no tsis zoo li yog vim qhov sib txawv ntawm cov koob tshuaj nitrate niaj hnub, uas zoo sib xws hauv peb qhov kev tshawb fawb (kwv yees li 0.1 mmol / kg / hnub), thiab tsis tuaj yeem piav qhia los ntawm tus neeg mob hnub nyoog, lub cev qhov hnyav lossis poj niam txiv neej. Txawm li cas los xij, qhov sib txawv ntawm cov tshuaj antihypertensive ib txhij, cov neeg mob pej xeem, kev noj nitrate hauv cov placebo thiab ntshav siab thaum lub sijhawm pib ntawm nitrate supplementation yuav ua rau muaj feem cuam tshuam. Lwm qhov kev sim tshuaj xyuas tau pom tias kev noj tshuaj nitrate ib hnub ib zaug (kwv yees li 0.1 mmol / kg / hnub) rau 6 lub lis piam txhim kho cov hlab ntsha hauv cov neeg mob hypercholesterolemia, uas cuam tshuam nrog kev txo qis hauv cov ntshav siab 62. Tej yam tshwm sim ntawm nitrate supplementation ntawm metabolic thiab/los yograumkev ua haujlwmtsis tau tshaj tawm hauv cov kev tshawb fawb soj ntsuam no.
Arterial txhav yog txuam nrog kev laus thiab yog ib qho kev pheej hmoo loj rau cov kab mob plawv xws li myocardial infarction thiab stroke. Kev tshuaj xyuas thiab kev tshuaj xyuas meta-tshaj tawm ntawm kev sim ntsuas randomized tau ua los kwv yees qhov cuam tshuam ntawm kev rov ua haujlwm nitrate (tsawg kawg 3 hnub) ntawm peripheral thiab central ntshav siab thiab arterial txhav hauv cov neeg noj qab haus huv thiab hauv cov neeg mob uas muaj kev pheej hmoo ntawm cov kab mob plawv vim Kev rog rog, ntshav siab, kab mob peripheral artery, hypercholesterolemia thiab / lossis plawv tsis ua haujlwm. Cov ntaub ntawv sib sau los ntawm 45 cov kev tshawb fawb siv kwv yees li 500mg nitrate ib hnub tau pom tias txo qis hauv systolic (txhais tau tias-2.91mmHg) thiab ntshav siab diastolic (txhais tau tias-1.45mmHg). Kev tshuaj xyuas cov ntaub ntawv los ntawm peb qhov kev sim uas ntsuas qhov nruab nrab (aortic) ntshav siab kuj pom tias txo qis nrog nitrate supplementation (txhais tau tias systolic -1.6 mmHg, txhais tau tias diastolic -2.0mmHg). Txawm li cas los xij, meta-kev tshuaj ntsuam pomTSIS MUAJ (nitric oxide)Qhov sib txawv tseem ceeb hauv cov teebmeem ntawm nitrate supplementation ntawm cov ntshav siab ntawm cov pab pawg ntawm cov neeg mob uas muaj kev noj qab haus huv sib txawv. Qhov tseem ceeb, qhov txo qis hauv cov ntshav siab nrog nitrate supplementation hauv qhov kev tshuaj ntsuam meta, thiab hauv kev tshuaj ntsuam meta ntawm cov ntaub ntawv los ntawm cov tib neeg noj qab haus huv 5415, yog piv nrog cov uas tau pom nyob rau hauv kev sim txo qis sodium kom tsawg thiab ntawm Kev Noj Qab Haus Huv Kev Noj Qab Haus Huv (DASH) kev noj zaub mov. ,1s ib. Kev tshuaj xyuas cov ntaub ntawv los ntawm xya qhov kev sim uas ntsuas qhov ntsuas qhov ntsuas qhov ntsuas thiab cov mem tes nthwv dej tshaj tawm pomTSIS MUAJ (nitric oxide)Cov txiaj ntsig tseem ceeb ntawm kev tswj hwm nitrate ntawm arterial stiffness83. Txawm li cas los xij, cov kws tshawb fawb tau sau tseg tias cov kev sim muaj nyob rau hauv cov tib neeg uas muaj cov kab mob plawv ntxiv (xws li mob ntshav siab, ntshav qab zib lossis hyperlipidemia) kuj tsawg thiab lawv cov kev soj ntsuam zoo li yuav tsis muaj zog los txheeb xyuas qhov sib txawv tseem ceeb. Cov kev tshawb fawb ntxiv yuav tsum tau kos cov lus pom zoo hauv cov pab pawg neeg mob no.
Zuag qhia tag nrho, cov pov thawj tam sim no rau lub sij hawm ntev txaus siab rau cov kab mob plawv ntawm nitrate supplementation hauv cov neeg mob uas muaj kab mob plawv, nrog rau kev kub siab, yog qhov tsis txaus ntseeg. Yog li ntawd, kev sim tshuaj loj ntxiv nrog ntau cov tshuaj nitrate yuav xav tau.
Cardiovascular teebmeem ntawmnitrate supplementationntawm lub raum ua haujlwm
Cov teebmeem metabolic.
Kev tswj cov metabolism tsis zoo nrog kev rog rog thiab hyperglycemia yog sib txuas nrog kev pheej hmoo ntawm DKD, uas cuam tshuam nrog cov txheej txheem glomerular thiab tubular mechanisms6617. Ntxiv nrog rau cov ntaub ntawv kho mob tau zoo ntawm ACE inhibitors thiab Ang IIrecep-tor blockers hauv cov neeg mob.raumua 6819, kev sim loj hauv kev sim tau pom tias kev kho mob nrog sodium / glucose co-transporter-2(SGLT2) inhibitors tuaj yeem txo qis albuminuria, kev pheej hmoo ntawm CKD (mob ntev raumkab mob)Kev loj hlob thiab kev mob plawv hauv cov neeg mob nrog T2DM thiabraumtug 7o. Cov txiaj ntsig zoo ntawm SGLT2inhibition tsis zoo li yuav tsum tau kho los ntawm kev txhim kho glycemic tswj. Kev sim ua pov thawj qhia tias lawv yuav tshwm sim los ntawm ntau yam glomerulotubular mechanisms, 17 xws li kev hloov kho ntawm cov lus teb myogenic thiab TGF nrog rau cov tubular reabsorption thiab muaj peev xwm hloov kho ntawm lub raum sympathetic paj hlwb. Cov txheej txheem no tuaj yeem muaj feem cuam tshuam ncaj qha rau NO (nitric oxide)bioactivity.
Cov nas uas tsis muaj eNOS (nitric oxide synthase)txhim kho ntshav siab7 thiab cov yam ntxwv zoo li cov mob metabolic (ie. hypertension, dyslipidemia, insulin tsis kam thiab rog) 17t. Tsis tas li ntawd, eNOS (nitric oxide synthase)deficiency nyob rau hauv nas yog txuam nrogmob rauml75-17 thiab nrawm nrawm ntawm CKD (mob ntev raumkab mob)ib 7817. Yuav luag ib xyoo caum dhau los, ntxiv nrog kev noj zaub mov noj ntawm nitrate tau pom tias rov qab cov yam ntxwv ntawm metabolic syndrome hauv cov nas uas tsis muaj eNOS. (nitric oxide synthase)15. Ntau qhov kev tshawb fawb tau tshawb pom txij li tau lees paub tias nitrate supplementation muaj cov txiaj ntsig zoo hauv metabolic, uas koom nrog kev hloov kho ntawm mitochondrial muaj nuj nqi thiab oxidative kev nyuaj siab, ua kom AMP-activated protein kinase (AMPK) kos npe thiab hloov kho cov phiaj xwm nqes nrog rau sterol regulatory element-binding protein 1. , acetyl-CoA carboxy-lase, nruab nrab-chain tshwj xeeb acyl-CoA dehydrogenase, mitochondrial thiab peroxisome proliferator-activated receptor-y coactivator la7, 181-184. Ib qho kev sib txuas ntawm nitrate thiab / lossis nitrite supplementation thiab AMPK activation kuj tau pom nyob rau hauv cov qauv kev sim ntawm lub plawv tsis ua hauj lwm nrog khaws cia ejection fraction1 thiab IRI ntawm lub plawv 18 nrog rau hauv kev tshawb fawb txog cov txiaj ntsig zoo ntawm qhov supplementation ntawm lub neej ntev 6. Kev paub txog cov txheej txheem tshwj xeeb ntawm AMPK ua kom muaj zog hauv ntau hom cell (piv txwv li, hepatocytes, adipocytes, skeletal leeg hlwb thiab cardiomyocytes) raug txwv, tab sis kev tshawb fawb tau qhia txog kev koom tes ntawm nitrate thiab / lossis nitrite-mediated modulation ntawm lub zog- Kev paub txog txoj hauv kev, suav nrog inhibition ntawm lub hom phiaj ntawm rapamycin6, ua kom sirtuin 3 (REF.18) thiab PKA, thiab kev hloov kho ntawm mitochondrial-derived ROs7,185.
Kev sim ua pov thawj qhia tias kev ntxiv nrog nitrate yuav yog ib qho tshiab, muaj kev nyab xeeb thiab pheej yig txoj kev kho mob rau cov neeg mob T2DM ntawm qhov muaj feem pheej hmoo ntawm kev tsim DKD8181,187.Tam sim no, ob peb qhov kev sim tshuaj tau sim cov txiaj ntsig zoo ntawm nitrate hauv cov neeg mob T2DM. Ib qho kev sim me me hauv 27 tus neeg mob uas muaj T2DM tsis pom muaj qhov cuam tshuam tseem ceeb ntawm 2 lub lis piam ntawm nitrate supplementation (250ml beetroot kua txiv txhua hnub) ntawm cardio-metabolic functions (uas yog, ntshav siab, endothelial function thiab insulin rhiab heev) 8. Lwm txoj kev tshawb fawb uas tau tshawb xyuas cov teebmeem metabolic ntev ntev ntawm cov tshuaj nitrate tsawg (250mg ib hnub rau 24 lub lis piam) hauv cov neeg mob T2DM pom tsis muaj qhov sib txawv tseem ceeb hauv kev tswj glycemic ntawm nitrate (n=35) thiab placebo pawg ( n{16}) 89. Yog vim li cas rau qhov tsis muaj txiaj ntsig ntawm ob txoj kev tshawb fawb no, uas sib piv nrog cov pov thawj kev sim ntau, yuav yog qhov tseeb tias yuav luag txhua tus neeg koom tau txais kev kho mob metformin, uas paub tias ua kom AMPK10.Nyob rau hauv tus qauv nas ntawm cov kab mob cardiometabolic, tsis muaj ntxiv. Cov txiaj ntsig zoo ntawm cov hlab plawv thiab cov kab mob metabolic tau pom thaum noj nitrate supplementation nrog metformin, qhia txog cov txheej txheem zoo sib xws. Kev tshawb fawb theem II uas tshawb xyuas cov teebmeem cardiometabolic ntawm nitrite therapy (40 mg, peb zaug ib hnub twg) rau 12 lub lis piam rau cov neeg laus uas muaj theem 1-2 kub siab, metabolic syndrome thiab ib txwm muaj.raummuaj nuj nqileej twg tsis tau txais cov tshuaj uas cuam tshuam rau cov metabolism hauv qabzib tau pom tias nitrite maj mam txo cov ntshav siab thaum thawj 8 lub lis piam ntawm kev kho mob (los ntawm kwv yees li -10 mmHg), tab sis cov ntshav siab tau pib rov qab mus rau qhov pib tom qab 10-12 lub lis piam. Hyperinsulinaemic-euglycaemic clamp cov kev tshawb fawb qhia tias nitrite supplementation ua rau muaj kev cuam tshuam rau kev txo qis cov piam thaj endogenous thiab txhim kho insulin rhiab heev. Strikingly, kev txhim kho tseem ceeb hauv carotid intima-media thickness thiab brachial artery endothelial muaj nuj nqi tau pom tom qab 12 lub lis piam ntawm kev kho nitrite.
Cov teebmeem metabolic ntawm NO (nitric oxide) ntawm lub raum ua haujlwm
Cov teebmeem rau lub raum.
Cov neeg mob nrog CKD (mob ntev raumkab mob)thiab cov nrograumua tsis tiavtau compromised NOS (nitric oxide synthase)muaj nuj nqi, txo NO (nitric oxide)bioactivity 819 thiab nce kev mob plawv thiab kev tuag. Tsis tas li ntawd, kev sib raug zoo ntawm lub raum nitrate clearance thiabraummuaj nuj nqitau pom nyob rau hauv cov neeg mob nrog CKD (mob ntev raumkab mob)0. Kev tshawb fawb hauv cov neeg laus thiab menyuam yaus nrograumua tsis tiavtau qhia tias peritoneal dialysis thiab hemodialysis sessions yog txuam nrog NO (nitric oxide)homeostasis, ntsuas raws li kev txo qis hauv cov qib ntawm nitrate, nitrite thiab cGMP (ib qho cim ntawm NO. (nitric oxide)teeb liab) 194-17. Cov kev tshawb fawb soj ntsuam yuav tsum tau tshawb xyuas cov nqi kho mob ntawm kev kho NO (nitric oxide)homeostasis, siv nitrate thiab/los yog nitrite supplementation, nyob rau hauv cov neeg mob uas muaj kev pheej hmoo siab.
Hauv ntau cov kev tshawb fawb sim, kev kho mob ntev nrog inorganic nitrate thiab nitrite tau cuam tshuam nrog kev kho mob xws li txo qis ntawmraumraug mobthiab preservation ntawmraumntshav khiav thiab GFR hauv cov qauv ntawmraumkab mobnrog los yog tsis muaj coexistent hypertension thiab kab mob metabolic 8.1s, nrog rau cov qauv nrog cov tshuaj pharmacological ntev ntawm NOS (nitric oxide synthase), unilateral nephrectomy ua ke nrog kev noj zaub mov siab 18, ob-raumib qho clip, deoxycorticosterone acetate ntsev, Ang II infusion920, kev laus thiabraumTSI [0203. Raws li cov kev tshawb fawb no, ntau lub tswv yim tau npaj los ua kom muaj txiaj ntsig zoo ntawm nitrate thiab nitrite supplementation. Cov no suav nrog dampening ntawm oxidative kev nyuaj siab los ntawm kev txo qis hauv NADPH oxidase kev ua, nce antioxidant muaj peev xwm ntawm superoxide dismutase, nce NO. (nitric oxide)bioactivity, txo qis hauv Ang II rhiab heev thiab hom I angiotensin II receptor qhia nyob rau hauv lub renovascular system, dampen-ing ntawm lub raum sympathetic paj hlwb thiab modulation ntawm lub cev tiv thaiv kab mob phenotypes thiab mitochondrial function8.
Hauv cov neeg laus noj qab haus huv, mob ntshav qab zib hom 2 ntawm nitrite koob tshuaj-raws li (0 58-5.21 mmol/kg/h) txo cov ntshav siab piv nrog cov placebo tab sis tsis muaj qhov cuam tshuam loj rau GFR ntsuas siv 5Cr-EDTA. clearance20,205. Cov lus teb ntshav siab no tau ntxiv rau hauv cov ntshav siab piv nrog cov neeg tsis muaj zog (txhais tau tias txo qis hauv cov ntshav siab ntawm 17 mmHg vs 10mmHg). Cov kws tshawb fawb tau pom tias qhov txo qis hauv cov ntshav siab tau cuam tshuam nrog kev txo qis hauv cov zis ntawm ENaCy thiab aqua-porin 2, tab sis qhov cuam tshuam ntawm nitrite infusion ntawm fractional sodium excretion tsis sib haum (uas yog, tsis hloov pauv, txo qis lossis nce ntxiv){{12 }}. Hauv cov tib neeg noj qab haus huv, cov teebmeem nitrite-mediated tsis cuam tshuam nrog kev hloov pauv hauv plasma lossis cov zis cGMP thiab tsis muaj kev cuam tshuam loj heev los ntawm kev inhibition ntawm XOR, ACE lossis carbonic anhydrase0. Ntxiv mus, kev noj zaub mov nitrate ntxiv (kwv yees li 0.1 mmol / kg / hnub) rau 1 lub lis piam tsis hloov pauv eGFR ( ntsuas siv creatinine tshem tawm) piv nrog cov placebo hauv cov txiv neej noj qab haus huv 20.
Kev tshuaj xyuas thiab kev tshuaj ntsuam xyuas meta uas tau tshawb xyuas ntau yam hloov pauv txoj kev ua neej tau pom tias kev noj zaub ntau dua txo qhov kev pheej hmoo ntawm CKD. (mob ntev raumkab mob)208. Qhov kev cuam tshuam no yuav cuam tshuam li cas rau kev noj nitrate ntau ntxiv. Txog niaj hnub no, tsis muaj cov tshuaj placebo-tswj tshuaj ntsuam xyuas tau tshawb xyuas qhov cuam tshuam ntawm cov tshuaj nitrate ntev ntev hauv cov neeg mob uas muajraumkab mob. Txawm li cas los xij, kev tshawb nrhiav kev sib tw hauv cov neeg mob CKD (mob ntev raumkab mob)(theem 2-4) vim muaj ntshav siab lossis ntshav qab zib nephropathies pom qhov txo qis ntawm cov ntshav siab thiab lub raum tiv thaiv qhov ntsuas 4h tom qab ib koob tshuaj nitrate (300mg) 2. Ntxiv mus, txoj kev tshawb fawb yav tom ntej nrog lub sijhawm ua raws li yuav luag 6 xyoo tau xaus lus tias ib txwm noj nitrate thiab / lossis nitrite los ntawm cov khoom noj khoom haus tau ua rau nws tus kheej cuam tshuam nrog kev txo qis ntawm kev kub siab thiab CKD. (mob ntev raumkab mob)210.
Ua ke, cov kev tshawb fawb soj ntsuam tau pom tias nitrate supplementation yog txuam nrog kev txo qis ntawm cov ntshav siab, uas zoo li hais tau ntau dua rau cov neeg mob ntshav siab. Hauv cov tib neeg noj qab haus huv, qhov txiaj ntsig no tsis cuam tshuam nrog kev hloov pauv loj hauvraummuaj nuj nqiTxawm li cas los xij, qhov txiaj ntsig zoo ntawm lub raum haemodynamics tau pom hauv cov neeg mob CKD (mob ntev raumkab mob). Nyob rau yav tom ntej, kev siv cov placebo-tswj, randomized sim yog xav tau los txiav txim siab yog tias ntxiv nrog inorganic nitrate thiab / lossis nitrite los kho NO (nitric oxide)bioactivity tuaj yeem yog ib qho kev kho mob ntxiv kom qeeb qhov kev loj hlob ntawmraumkab mobthiab cuam tshuam cov hlab plawv thiab cov kab mob metabolic. Cov teebmeem zoo li no tsis tu ncua tau tshaj tawm hauv cov kev tshawb fawb sim.
CKD (mob ntev raumkab mob): Ua li casTSIS MUAJ (nitric oxide) cuam tshuamraumkab mob
Cov lus xaus thiab cov kev xav yav tom ntej
Ntau xyoo dhau los txij li qhov kev tshawb pom ntawm NO (nitric oxide)Raws li qhov tsis txaus ntseeg ntawm endothelium-derived los ntawm kev so kom txaus, tab sis qee qhov kev tsis sib haum xeeb tseem muaj nyob rau ntawm nws qhov tsim thiab qhov tseeb ntawm cov teeb liab molecule, nrog rau nws cov teeb liab qis thiab qhov chaw cuam tshuam hauv kev noj qab haus huv thiab kab mob. TSIS MUAJ (nitric oxide)thiab lwm yam bioactive nitrogen oxide hom muaj lub luag haujlwm tseem ceeb hauv ntau yam kev ua haujlwm ntawm lub cev, suav nrog kev hloov kho ntawm lub cev.raum, mob plawv thiab metabolic systems. TSIS MUAJ (nitric oxide)yog classical muab los ntawm L-arginine-dependent NOS (nitric oxide synthase)isoforms, tab sis kuj tuaj yeem tsim endogenously ntawm serial txo cov kauj ruam ntawm inorganic nitrate thiab nitrite. Qhov no nitrate-nitrite-NO (nitric oxide)txoj hauv kev, uas tuaj yeem txhawb nqa los ntawm kev noj zaub mov, yog qhov tseem ceeb tshwj xeeb hauv cov xwm txheej uas ua haujlwm ntawm NOS (nitric oxide synthase)Qhov system txo qis lossis tsis ua haujlwm (uas yog, hypoxia, ischemia thiab pH qis). Downstream signaling thiab functional effects linked with two cGMP-dependent and -independent mechanisms. Txo NO (nitric oxide)bioactivity vim muaj kev cuam tshuam NO (nitric oxide)tiam los yog nce metabolism tau txuam nrog kev laus thiabraum, kab mob plawv thiab cov kab mob metabolic, uas feem ntau ua ke nrog cov cim ROS nce ntxiv ua rau oxidative kev nyuaj siab. Hauvraum, TSIS (nitric oxide)Nws yog ib qho tseem ceeb rau kev koom tes hauv autoregulation thiab kev hloov pauv ntawm tubular thauj, uas tej zaum yuav yog qhov tseem ceeb hauv kev txhim kho thiab kev loj hlob ntawm kev kub siab, CKD. (mob ntev raumkab mob), ischaemia-reperfusion raug mob thiab DKD. Txawm hais tias ntau qhov kev tshawb fawb sim tau pom tias muaj txiaj ntsig zoo ntawm nitrate thiab nitrite ntxiv rauraumkab mobthiab cov teeb meem cuam tshuam, cov txiaj ntsig no tos kev txhais lus kho mob ntxiv. Cov tswv yim tshiab uas twb muaj lawm thiab yav tom ntej uas nce NObioactivity thiab txo oxidative kev nyuaj siab, ntawm ob qho tib si pharmacological thiab kev noj haus, yuav muaj peev xwm kho tau los tiv thaiv thiab kho.raumkab mobthiab cuam tshuam cov teeb meem cardiometabolic. Ib qho ntawm cov teeb meem nrog cov neeg sib tw tshuaj tshiab no yog txhawm rau txhim kho lawv qhov chaw nyob thiab lub sijhawm xa mus kom ua tiav cov txiaj ntsig xav tau yam tsis muaj kev cuam tshuam tsis zoo hauv lub cev lub cev redox signaling.