Cov teebmeem ntawm L-Arginine Thiab -Adrenergic Receptor Ntawm Txoj Cai Ntawm Lub Raum Ua Haujlwm

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TSEEM CEEB: Lub raum yog ib qho tseem ceeb ntawm lub cev. Nrog rau ob qho tib si excretory thiab endocrine ua haujlwm, nws ua lub luag haujlwm tseem ceeb hauv kev tswj hwm lub cev lub cev ib txwm muaj. Raws li ib tug precursor ntawm nitric oxide (NO) synthesis nyob rau hauv zit, L-arginine yog koom nyob rau hauv intracellular thiab intercellular signaling ntawm NO, ib tug vasoactive yam yog li plays ib tug tseem ceeb caij nyob rau hauv kev tswj lub cev physiological zog ntawm lub raum. Alpha-adrenergic receptor (,-AR) kho cov paj hlwb kom tswj tau lub plawv, cov hlab ntsha, thiab lub paj hlwb ntawm lub cev. Q-AR faib nyob rau hauv vascular du nqaij feem ntau kho vasoconstriction. Kev ua haujlwm ntawm ,-AR rau adrenergic agonists txo qis hauv cov qauv nas ntawm lub raum tsis ua haujlwm, ntshav qab zib, kub siab, thiab sab laug ventricular hypertrophy, uas cuam tshuam rau lub xeev hemodynamic thiab vascular tone ntawm lub raum. Ntawm no peb txheeb xyuas txoj hauv kev uas

L-arginine txhim kho lub teb ntawm y-AR rau nws cov agonists los ntawm elucidating hom kev ua f NO / ;-AR thiab lawv cov teebmeem ntawm lub raum ua haujlwm.

Lo lus tseem ceeb: L-arginine; nitric oxindole; - adrenergic receptor; raum

Raws li lub teb chaws uas muaj cov neeg coob coob nyob hauv lub ntiaj teb, nrog kev laus ntawm cov pej xeem, qhov kev pheej hmoo ntawm cov kab mob ntev tau nce siab dua, ntawm cov uas.mob raum mobtau mus txog 10.8 feem pua, uas yog ib qho ntawm "cov neeg tua tsis pom" uas ua phem rau pej xeem kev noj qab haus huv. Nyob rau hauv xyoo tas los no, kev tshawb fawb ntawmlub raum ua haujlwmtau nyiam ntau yam, tshwj xeeb tshaj yog kev tshawb fawb txog kev tiv thaiv thiab kev kho mob raum kab mob, thiab kev txhim kho lub raum ua haujlwm tseem ceeb tshwj xeeb. L-arginine yog cov neeg nqa khoom muaj nitrogen ntau tshaj plaws hauv cov nqaij mos hauv lub cev thiab yog lub hauv paus rau kev sib txuas ntawm polyamines thiab nitric oxide (nitric xide, NO), thiab lwm yam molecules muaj zog hauv lub cev. TSIS yog ib qho tseem ceeb endogenous gas signal molecule, uas tuaj yeem tso tawm los ntawm cov neurons thiab tuaj yeem tsim los ntawm cov ntaub so ntswg ntawm lub cev xws li lub plawv, lub hlwb,daim siab, raum, thiab plab hnyuv. Nws yog koom nrog hauvmob plawv, ntshai, thiablub cev tiv thaiv kab mobntawm lub cev. Nws plays lub luag haujlwm tseem ceeb hauv ntau yam txheej txheem physiological thiab pathological. Cov kev tshawb fawb tau pom tias TSIS yog qhov tseem ceeb rau kev tswj hwm lub raum ua haujlwm. , Adrenergic receptors (-adrenergic receptor, -AR) yog dav faib nyob rau hauv ntau yam ntaub so ntswg hlwb ntawm lub cev thiab koom nyob rau hauv cov kev cai ntawm glycogenolysis, vasoconstriction, cardiac inotropy, thiab lwm yam physiological teebmeem. Cov kev tshawb fawb tau pom tias qhov tshwm sim ntawm kev kub siab, sab laug ventricular hypertrophy (LVH) thiab kab mob raum muaj feem cuam tshuam rau qhov tsis muaj NO hauv lub cev, thiab exogenous L-arginine muaj txiaj ntsig zoo rau kev txhim kho cov kab mob no. Kev ua haujlwm ntawm ;-AR rau adrenergic agonists tau txo qis hauv lub raum tsis ua haujlwm thiab LVH nas piv rau cov nas noj qab haus huv. Tsis ntev los no, Ahmad et al. tau qhia tias exogenous TSIS MUAJ precursors tuaj yeem tswj cov endothelial nitric xide synthase (eNOS) / NO / cyclic guanosine momo-phosphate (cGMP) txoj hauv kev hauv LVH nas thiab ,-AR reactivity, nthuav tawm thawj zaug uas muaj kev cuam tshuam ntawm q;-AR thiab TSIS MUAJ precursors, tab sis hom kev txiav txim ntawm ob thiab lawv cov teebmeem ntawm kev tswj lub raum ua haujlwm tseem tsis tau meej meej. Yog li, tsab xov xwm no tshuaj xyuas lub luag haujlwm ntawm L-arginine thiab ;-AR hauv kev tswj hwm lub raum ua haujlwm, txhawm rau muab cov ntaub ntawv siv rau kev kho mob.

Nyem rau kawm cistanche tubulosa extract cov txiaj ntsig

Generation ntawm NO thiab kev tswj lub raum ua haujlwm

Kev tsim cov L-arginine thiab TSIS TAU Cov amino acid tseem ceeb L-arginine yog cov khoom siv ua ntej ntawm ntau yam khoom siv roj ntsha hauv lub cev. Lub cev siv L-arginine ua raw khoom thiab ua tiav cov synthesis ntawm endogenous NO nrog kev koom tes ntawm oxygen, nitric x-ide synthase (NOS), thiab ib tug me me ntawm txo coenzyme II (NADPH). Tam sim no, muaj peb subtypes ntawm NOS paub: endothelial, neuronal, thiab inducible. Raws li ib qho kev so ntawm endothelial, cov hlwb endothelial tsis tsuas yog txuas ntxiv ua ke thiab zais NO hauv lub xeev basal, tab sis kuj tso NO rau vascular du nqaij thaum txhawb nqa los ntawm acetylcholine, bradykinin, platelets sib sau ua ke, thiab kev hloov pauv hauv cov ntshav txaus siab. Ib tug series ntawm kev ua exert vasodilatory teebmeem. Muaj ob hom kev ua haujlwm tseem ceeb ntawm NO. Ib qho yog cGMP-nyob ntawm txoj kev. TSIS MUAJ tsim los ntawm cov hlwb endothelial diffuses mus rau vascular du leeg hlwb thiab activates soluble guanylate cyclase (sGC), uas catalyzes guanosine cyclase. Triphosphate hloov mus rau hauv cGMP, thiab cov protein kinase G tau qhib los ntawm kev txhawb nqa ntawm cGMP thiab ua rau cov hom phiaj sib txawv rau phosphorylate, yog li koom nrog hauv vasodilation, thiab neutrophil activation, thiab lwm yam. Lwm qhov yog txoj hauv kev cGMP-kev ywj pheej, uas yog, TSIS ncaj qha ntxiv ib pawg nitroso rau cysteine ​​residue ntawm lub hom phiaj protein los ntawm S-nitrosylation los tswj kev ua haujlwm ntawm lub hom phiaj protein.

Cov txiaj ntsig ntawm NO ntawm kev tswj hwm lub raum ua haujlwm Raws li qhov tseem ceeb vasodilator hauv lub cev, TSIS tuaj yeem tswj hwm vascular nro thiab ntshav ntws los ntawm kev so cov leeg nqaij leeg, inhibiting cov leeg nqaij pob txha, inhibiting platelet aggregation, thiab ua kom cov leukocytes, cuam tshuam rau vascular. remodeling thiab vasodilation. Qhov cuam tshuam ntawm NO ntawm kev tswj lub raum ua haujlwm tseem ceeb heev. Piv txwv li, TSIS muaj peev xwm tswj tau qhov kev ua haujlwm ntawm lub cev sib txuas ntawm lub raum, cuam tshuam rau reabsorption ntawm Na * thiab dej, thiab tswj qhov sib npaug ntawm cov dej thiab ntsev. Podocytes yog hom cell loj uas tsim cov txheej txheem visceral ntawm lub raum capsule thiab ib feem tseem ceeb ntawm glomerular filtration barrier. Tsis muaj catalyzed los ntawm eNOS muaj qee yam kev tiv thaiv ntawm glomerular podocytes. Bachmann et al. kawm txog kev qhia ntawm eNOS nyob rau hauv lub raum los ntawm immunohistochemistry thiab lwm yam kev sim thiab pom tias eNOS protein feem ntau yog faib nyob rau hauv endothelial hlwb ntawm afferent thiab efferent arterioles, glomerular capillaries, intrarenal hlab ntsha, thiab medullary ncaj cov hlab ntsha me me, nws tus kheej thiab tsim NO tuaj yeem txhim kho. Kev ua haujlwm ntawm lub raum cov hlab ntsha, koom nrog kev tswj hwm ntawm lub raum ntshav khiav thiab lub raum medulla ntshav perfusion, cuam tshuam rau glomerular filtration tus nqi, tswj lub raum sympathetic paj hlwb thiab inhibit platelet adhesion thiab aggregation thaum lub sij hawm o. Tsis muaj qhov tsis txaus yog tshwm sim hauv cov kab mob raum, xws li TSIS muaj qhov tsis txaus tuaj yeem cuam tshuam rau lub raum sodium excretion, lub raum vasculature elasticity, thiab lub raum reabsorption thiab excretion. Tsis tas li ntawd, renal matrix remodeling yuav kawg ua rau lub raum puas. Kev tsim cov matrix thiab nws cov tsub zuj zuj hauv lub raum yog cuam tshuam nrog qhov tsis muaj NO hauv vivo. TSIS TAU tseem koom nrog hauv cov txheej txheem pathological ntawm glomerulosclerosis.

Kev nthuav qhia ntawm -AR thiab kev tswj hwm lub raum ua haujlwm

Cov qauv thiab kev faib tawm ntawm -AR -AR yog G protein-coupled receptor nrog 7 transmembrane qauv, muaj 3 intracellular thiab 3 extracellular voj qauv, nws N-terminus nyob extracellularly, thiab nws C-terminus nyob rau hauv intracellular. Lub C-terminus ntawm peptide saw thiab qhov thib ob thiab thib peb intracellular loops muaj qhov chaw khi rau G protein (guanylate binding protein), uas tuaj yeem tsim teeb liab hloov pauv los ntawm kev sib txuas nrog G protein. Xyoo 1985, International Union of Pharmacology tau faib -ARs rau hauv raws li qhov sib txawv ntawm cov khoom siv tshuaj. -AR, u-AR thiab up-AR 3 subtypes. ;-AR yog dav faib nyob rau hauv lub cev nqaij daim tawv thiab lub cev, ntawm uas x-AR feem ntau yog faib nyob rau hauv lub hlwb, cov hlab ntsha, plawv, siab, adrenal caj pas, thiab vas deferens, thiab ib feem me me yog faib nyob rau hauv lub prostate thiab lub raum; piv nrog rau lwm cov ntaub so ntswg, u-AR yog nyob rau hauv Kev faib yog siab dua nyob rau hauv lub hlwb thiab lub plawv, whereas up-AR tsuas yog muaj nyob rau hauv lub hlwb. Feng et al. kawm nas raum ;-AR thiab pom tias nws muaj ntau tshaj plaws faib rau hauv lub raum cortex, thiab nws qhov ntom ntom ntawm lub raum cortex mus rau lub raum papilla; qhov ntom ntawm u-AR thiab u-AR nyob rau hauv lub raum yuav luag tib yam nyob rau hauv lub cortex thiab medulla. Ib yam li ntawd, peb lub subtypes ntawm -AR, ug-AR, thiab up-AR tau yuav luag sib npaug sib npaug hauv qhov sib npaug ntawm cov tubules.

Lub luag haujlwm thiab hom ntawm -AR -AR tuaj yeem koom nrog hauv kev tswj hwm kev ua haujlwm ntawm cov ntaub so ntswg thiab hlwb los ntawm ntau txoj hauv kev. Raws li G protein-coupled receptor, -AR tuaj yeem ua los ntawm kev xa xov thib ob, uas yog, phospholipase C ntawm plasma membrane yog qhib los ntawm Gq / 11 protein kom hydrolyze phospholipid molecule phosphatidylinositol diphosphate rau thawj Ob tug tub txib molecules inositol thiab triphosphate. diacylglycerol. Inositol triphosphate tuaj yeem khi thiab qhib cov calcium ion raws ntawm endoplasmic reticulum lossis tonoplast membrane kom tso cov calcium ions sab hauv; diacylglycerol tuaj yeem khi thiab qhib cov protein kinase C kom ua rau muaj kev cuam tshuam ntau. -AR kuj activates ntau lwm yam effectors, nrog rau cov mitogen-activated protein kinase txoj kev, cyclic adenosine monophosphate metabolism, thiab lwm yam. Tsis tas li ntawd, ,-AR activates mitochondria thiab tswj cell proliferation thiab loj hlob.

Kev tswj ntawm lub raum ua haujlwm los ntawm -AR Ntau qhov kev tshawb fawb tau pom tias TSIS muaj kev tswj hwm ntawm lub raum ua haujlwm. Txawm li cas los xij, muaj qee qhov kev tshawb fawb tsom rau kev tswj hwm ntawm ,-AR ntawm lub raum ua haujlwm. Cov kev tshawb fawb tau pom tias kev ua kom tsis zoo ntawm ,-AR txhawb nqa qhov kev qhia ntawm cov teeb meem nuclear-kB kom ua rau mob, ua rau cov cellular matrix deposition, raum tubulointerstitial fibrosis, thiab lwm lub raum matrix remodeling, thiab thaum kawg ua rau lub raum puas. Hauv vitro thiab hauv vivo kev sim tau pom tias u thiab -AR ua lub luag haujlwm tseem ceeb hauv epinephrine-mediated vasoconstriction hauv ob qho tib si thiab muaj kab mob, thiab p-AR tuaj yeem sib koom ua ke nrog ;, -AR los kho lub raum vasoconstriction. , thiab cov nas hypertensive ua rau lub raum tsis ua haujlwm kom ua rau muaj kev ua haujlwm ntawm un-AR. ,-AR-mediated lub raum vasoconstriction tuaj yeem cuam tshuam rau lub raum ntshav perfusion, kev tswj hemodynamic, thiab lwm yam, thiab tseem ceeb heev rau kev saib xyuas ntawm lub raum ua haujlwm. Hauv cov kab mob xws li lub raum tsis ua haujlwm thiab mob ntshav qab zib mellitus, kev ua haujlwm ntawm ,-AR rau agonists tau txo qis, qhia txog qhov tseem ceeb ntawm -AR hauv kev tswj hwm lub raum ua haujlwm.

L-arginine thiab -AR txoj kev

Lee et al. qhia tau hais tias ib qho exogenous mov ntawm L-arginine tuaj yeem kho lub plawv norepinephrine hyperactivity nyob rau hauv cov nas hypertensive spontaneously los ntawm up-regulating NOS / sGC / cGMP txoj kev. Cov kev tshawb fawb tau pom tias muaj zog ntxiv rau lub raum oxidative kev ntxhov siab thiab txo qis ntawm eNOS attenuate raum u-AR teb hauv LVH nas. Qhov txo qis ntawm basal raum cortical perfusion thiab -AR vasoconstrictor cov lus teb hauv LVH nas yog cuam tshuam nrog kev txo qis ntawm eNOS/NO txoj hauv kev. Kev kawm los ntawm Ahmad et al. qhia tau hais tias kev sib cuam tshuam ntawm exogenous TSIS precursor thiab ,-AR qhia tias TSIS MUAJ precursor tuaj yeem tswj hwm eNOS / NO / cGMP txoj hauv kev hauv lub raum ntawm LVH nas, thiab ua rau u-AR, u-AR, thiab p-AR cuam tshuam nrog ib leeg. Ua kom muaj kev teb rau adrenergic agonists.

Kev tswj hwm los ntawm G-proteins Hauv glomeruli, qhov kev qhia ntawm eNOS yog nyob hauv cov hlwb endothelial, thaum neuronal NOS feem ntau yog qhia hauv cov quav hniav densa. TSIS tsim cov vasodilation nyob rau hauv cGMP-raws li nyob rau hauv ib tug tshwj xeeb spatial qauv, piv txwv li, TSIS diffuses rau lub glomerulus, thiab activates SCC nyob rau hauv endothelial hlwb kom nce cGMP theem, uas ntxiv activates protein kinase G ua los ntawm phosphorylating lub hom phiaj proteins. Cov txiaj ntsig saum toj no qhia tias TSIS ua haujlwm los ntawm kev tswj hwm qib ntawm tus xa xov thib ob-cGMP hauv G protein txoj hauv kev. Xav tias ,-AR ua raws li G protein-coupled receptor, nws hom kev ua haujlwm yog los ntawm kev xa xov thib ob. . Yog li ntawd, TSIS MUAJ precursors yuav tswj,-AR teb los ntawm G proteins.

Kev tswj hwm los ntawm -arrestin -arrestin yog ib qho adapter protein thiab cov teeb liab transduction regulatory protein uas yog ib qho tseem ceeb hauv G protein-coupled receptor-txog teeb liab transduction. Tam sim no muaj plaub tus tswv cuab ntawm tsev neeg raug ntes, qhov pom kev ntes (arrestin 1 thiab 4) thiab tsis pom kev ntes (arrestin 2 thiab 3, tseem hu ua -arrestin 1 thiab 2). Lawv yog cov qauv zoo sib xws, muaj txog 400 amino acid residues, nrog rau cov qauv kev txuag tau zoo, nrog rau ob daim ntawv tiv thaiv sib luag, N-terminal thiab C-terminal domains, feem. Tom qab G protein-coupled receptors tau qhib thiab phosphorylated los ntawm agonists, lawv tuaj yeem lees paub los ntawm -arrestin thiab khi rau nws, thiab inhibit qhov kev sib txuas ntawm G proteins thiab receptors los ntawm kev tsim cov steric hindrance, yog li txiav los yog tsis muaj zog cov receptors kho cov teeb liab txoj hauv kev. -arrestin tsis tsuas yog koom nrog hauv kev sib koom ua ke, desensitization, thiab degradation ntawm G protein-coupled receptors tab sis kuj ua raws li ib qho kev taw qhia molecule los kho -AR teeb liab transduction. Tsis ntev los no, Hayashi et al. pom qhov sib txuas ntawm -arrestin thiab ,-AR, uas yog nitrosylation ntawm ib qhov chaw tshiab ntawm -arrestin xaiv inhibits -arrestin nws tus kheej raws li ib qho kev taw qhia molecule-mediated txoj kev, thov ib tug dav mechanism rau -arrestin-biased teeb liab transduction los ntawm G protein-coupled receptors . Nyob rau tib lub sijhawm, Ozawa et al. kuj tau pom qhov sib txuas ntawm NO, -arrestin, thiab ;-AR, uas yog, -arrestin cuam tshuam nrog ib leeg cysteine ​​los ntawm eNOS thiab yog nitrosylated, thiab nws cov dynamic S -Nitrosylation thiab denitration modulate stimulus-induced G protein txoj hauv kev. Raws li NO's cGMP-kev ywj pheej hom ntawm kev txiav txim, TSIS muaj kev tswj hwm -AR teb rau agonists los ntawm nitrosylation ntawm -arrestin.

Hauv kev xaus, lub raum tsis yog tsuas yog lub cev excretory ntawm lub cev tab sis kuj yog ib qho tseem ceeb ntawm cov kab mob endocrine, uas ua lub luag haujlwm tseem ceeb hauv kev tswj hwm lub cev ntawm lub cev. Nyob rau hauv xyoo tas los no, kev tshawb fawb txog kev tiv thaiv thiab kev kho mob ntawm lub raum kab mob thiab kev txhim kho lub raum kev ua haujlwm tau nyiam ntau yam. Raws li cov vasodilator yam tseem ceeb, TSIS yog qhov tseem ceeb los tswj lub raum ua haujlwm ib txwm muaj, thaum ,-AR koom nrog kev tswj hwm lub raum vasoconstriction, thiab txo qis ntawm nws cov lus teb ncaj qha lossis tsis ncaj qha cuam tshuam rau lub raum ua haujlwm. Hauv daim ntawv no, los ntawm kev sib tham txog kev ua haujlwm thiab hom kev ua ntawm NO thiab -AR, lub luag haujlwm thiab kev tswj hwm ntawm L-arginine thiab -AR hauv kev tswj hwm lub raum kev ua haujlwm tau txheeb xyuas, thiab nws tau qhia meej tias TSIS TAU ua ntej- tswj lub raum. NO / cGMP txoj hauv kev thiab ua rau lub raum Txoj hauv kev ntawm kev txhim kho,-AR cov lus teb muab cov lus qhia rau kev kawm txog cov txheej txheem ntawm kev mob raum mob thiab muab lub hauv paus theoretical rau kev kawm txog cov tshuaj tshiab.