目的探讨Urocortin(Ucn)对自发性高血压大鼠(SHR)胸主动脉舒缩功能的作用及机制。方法采用体外血管灌流,观察Ucn对SHR胸主动脉的舒张作用,以及左旋硝基精氨酸甲酯(N(ω)n itro-L-argin ine methyl ester,L-NAME)、亚甲蓝(M ethylene B l...目的探讨Urocortin(Ucn)对自发性高血压大鼠(SHR)胸主动脉舒缩功能的作用及机制。方法采用体外血管灌流,观察Ucn对SHR胸主动脉的舒张作用,以及左旋硝基精氨酸甲酯(N(ω)n itro-L-argin ine methyl ester,L-NAME)、亚甲蓝(M ethylene B lue,MB)和格列本脲(G lybenc lam ide)对其舒张作用的影响。结果Ucn(1 nmol.L-1~1μmol.L-1)可明显舒张内皮完整和去内皮SHR胸主动脉(P<0.01),此作用具有剂量依赖性;一氧化氮(NO)合成酶抑制剂L-NAME(100μmol.L-1)和鸟苷酸环化酶(GC)抑制剂MB部分抑制Ucn舒张血管的作用,而且增强去甲肾上腺素(NE)产生的收缩反应。ATP敏感钾通道(KATP)阻断剂格列本脲(10μmol.L-1)可减弱Ucn的舒血管作用。结论Ucn对SHR血管具有内皮依赖性和非内皮依赖性舒张作用,此作用部分是Ucn增加血管内皮细胞NO水平实现的,并且与NO-cGMP通路和KATP通道有关。展开更多
Urocortin,a novel peptide of the cortiotropin releasiong hormone(CRH)family,was discovered in 1995 in the rat brain and subsequently cloned and localized to human chromosome 2.It can bind to both CRH type 1 receptor a...Urocortin,a novel peptide of the cortiotropin releasiong hormone(CRH)family,was discovered in 1995 in the rat brain and subsequently cloned and localized to human chromosome 2.It can bind to both CRH type 1 receptor and CRH type 2 receptor,as well as CRH binding protein.Especially to CRH type 2 receptor,urocortin binds to it with 40 times more potency than CRH does.Therefore,urocortin is thought to be an endogenous ligand for CRH type 2 receptor.Immunoreactive urocortin and urocortin mRNA were localized in many areas such as mammalian brain,cardiovascular system,placenta.It is believed that urocortinmay play important physiological roles as a neuropeptide not only in the central nervous system but also in peripheral tissues.展开更多
OBJECTIVE Urocortins(UCNs)and transforming growth factor-β(TGF-β)have been demonstrated to participate in various cardiovascular diseases,many of which involve VSMCs proliferation.And cytosolic phospholipase A2(c PL...OBJECTIVE Urocortins(UCNs)and transforming growth factor-β(TGF-β)have been demonstrated to participate in various cardiovascular diseases,many of which involve VSMCs proliferation.And cytosolic phospholipase A2(c PLA2)-mediated arachidonic acid(AA)release is an important cause of vascular smooth muscle cells(VSMCs)proliferation.The work was to investigate the regulation of VSMCs proliferation by UCN/TGF-βand whether c PLA2 was a link between their signaling pathways.METHODS VSMC proliferation was measured by MTT assay and immunofluorescence microscopy.Using cell flow cytometry,the changes in the cell cycle phases were investigated.si RNA was used to knockdown Smad2 and smad3 genes.Lentiviral Vector Particle was performed to over express c PLA2 gene.RESULTS Both UCN and TGF-βinhibited VSMCs proliferation and an additive effect was observed when the cells were treated with UCN plus TGF-β.TGF-βincreased the percentage of cells in G1-phase while UCN increased the cell percentage in G2-phase with a concomitant decrease in S-phase.Neither knockdown of smad2 nor smad3 reversed the role of TGF-β.Furthermore,c PLA2expression was increased by TGF-βbut decreased by UCN and UCN attenuated TGF-β-induced c PLA2 expression.In primary VSMCs,TGF-βinduced c PLA2 phosphorylation,and this effect was also attenuated by UCN.Similar to UCN,the c PLA2 inhibitor,pyrrophenone(PYR),also played a role in enhancing TGF-β-mediated mitoinhibition.Inversely,over-expression of c PLA2 eliminated the effect of UCN on the mitoinhibition.CONCLUSION The pretreatment with UCN counteracted TGF-β-mediated c PLA2 expression and activation,thereby contributing to TGF-β-mediated mitoinhibition of VSMCs.展开更多
文摘Urocortin,a novel peptide of the cortiotropin releasiong hormone(CRH)family,was discovered in 1995 in the rat brain and subsequently cloned and localized to human chromosome 2.It can bind to both CRH type 1 receptor and CRH type 2 receptor,as well as CRH binding protein.Especially to CRH type 2 receptor,urocortin binds to it with 40 times more potency than CRH does.Therefore,urocortin is thought to be an endogenous ligand for CRH type 2 receptor.Immunoreactive urocortin and urocortin mRNA were localized in many areas such as mammalian brain,cardiovascular system,placenta.It is believed that urocortinmay play important physiological roles as a neuropeptide not only in the central nervous system but also in peripheral tissues.
基金The project supported by National Natural Science Foundation of China(81573424&81273510)Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘OBJECTIVE Urocortins(UCNs)and transforming growth factor-β(TGF-β)have been demonstrated to participate in various cardiovascular diseases,many of which involve VSMCs proliferation.And cytosolic phospholipase A2(c PLA2)-mediated arachidonic acid(AA)release is an important cause of vascular smooth muscle cells(VSMCs)proliferation.The work was to investigate the regulation of VSMCs proliferation by UCN/TGF-βand whether c PLA2 was a link between their signaling pathways.METHODS VSMC proliferation was measured by MTT assay and immunofluorescence microscopy.Using cell flow cytometry,the changes in the cell cycle phases were investigated.si RNA was used to knockdown Smad2 and smad3 genes.Lentiviral Vector Particle was performed to over express c PLA2 gene.RESULTS Both UCN and TGF-βinhibited VSMCs proliferation and an additive effect was observed when the cells were treated with UCN plus TGF-β.TGF-βincreased the percentage of cells in G1-phase while UCN increased the cell percentage in G2-phase with a concomitant decrease in S-phase.Neither knockdown of smad2 nor smad3 reversed the role of TGF-β.Furthermore,c PLA2expression was increased by TGF-βbut decreased by UCN and UCN attenuated TGF-β-induced c PLA2 expression.In primary VSMCs,TGF-βinduced c PLA2 phosphorylation,and this effect was also attenuated by UCN.Similar to UCN,the c PLA2 inhibitor,pyrrophenone(PYR),also played a role in enhancing TGF-β-mediated mitoinhibition.Inversely,over-expression of c PLA2 eliminated the effect of UCN on the mitoinhibition.CONCLUSION The pretreatment with UCN counteracted TGF-β-mediated c PLA2 expression and activation,thereby contributing to TGF-β-mediated mitoinhibition of VSMCs.
