跳到主要內容

臺灣博碩士論文加值系統

(44.222.189.51) 您好!臺灣時間:2024/05/20 13:20
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:李慧欣
研究生(外文):Hui-Hsin Lee
論文名稱:血管周圍脂肪組織在正常和高血壓鼠的血管張力調控之角色
論文名稱(外文):Roles of Perivascular Adipose Tissue in Vascular Regulation in Normotensive and Hypertensive Rats
指導教授:吳錦楨
指導教授(外文):Chin-Chen Wu
口試委員:吳錦楨顏茂雄李哲夫樓迎統林琬琬陳秀珍曹正明
口試委員(外文):Chin-Chen WuMao-Hsiang YenTony J.F. LeeYing-Tung LauWan-Wan LinShiu-Jen ChenCheng-Ming Tsao
口試日期:2015-05-18
學位類別:博士
校院名稱:國防醫學院
系所名稱:生命科學研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:中文
論文頁數:157
中文關鍵詞:血管周圍脂肪組織一氧化氮微囊蛋白-1高血壓血管反應性胸主動脈
外文關鍵詞:perivascular adipose tissuenitric oxidecaveolin-1hypertensionvascular reactivityaorta
相關次數:
  • 被引用被引用:0
  • 點閱點閱:243
  • 評分評分:
  • 下載下載:24
  • 收藏至我的研究室書目清單書目收藏:0
簡介:由血管周圍脂肪組織 (perivascular adipose tissue, PVAT)釋出的脂肪細胞激素已被認為是一種調控血管張力的旁泌素。先前已有學者證實PVAT能夠抑制內皮型一氧化氮合成酶 (endothelial nitric oxide synthase, eNOS)合成釋出的一氧化氮 (nitric oxide, NO)。在高血壓疾病當中可以觀察到內皮細胞功能被抑制的情形。而調控eNOS的微囊蛋白-1 (caveolin-1, Cav-1)也被發現在自發性高血壓鼠 (spontaneously hypertensive rat, SHR)的胸主動脈中有被抑制的情形。此外,內皮衍生血管收縮因子之一的前列環素 (prostacyclin, PGI2)也被認為在SHR中能夠透過血栓素A2受體 (thromboxane A2 receptor, TP receptor)造成內皮細胞功能受損。活化TP receptor能夠使Ras homolog gene family member A (RhoA)/RhoA蛋白激酶 (Rho-associated kinase, ROK)移動到平滑肌細胞膜上,並導致鈣離子致敏感性。由於Cav-1與RhoA在小鼠胸主動脈中有結合在一起的情形,因此我們認為Cav-1有可能參與在RhoA/ROK的訊息傳遞路徑當中。綜觀以上可以發現,Cav-1不僅僅能夠調控血管張力,也能如同PVAT一般調控eNOS功能。因此,PVAT對於血管張力的調控是值得在高血壓引起內皮受損的機轉去探討的。
材料與方法:以Wistar大鼠(200 ~ 300 g)的胸主動脈做血管張力實驗,在有無PVAT培養溶液 (incubated solution)的情況下觀察其血管反應性以及內皮功能的表現,之後再合併給予不同抑制劑觀察PVAT incubated solution的作用是否能被抑制。將剩餘的胸主動脈與PVAT incubated solution反應15分鐘後磨碎,測量具有調控NO的相關蛋白質之表現量,包括:eNOS、phosphorylated-eNOSThr495 (p-eNOSThr495)、p-eNOSSer1177、AMPK和Cav-1,以及NO的濃度。之後,使用SHR (12週齡)以及相同週齡的Wistar-Kyoto (WKY)來研究脂肪對不同血壓大鼠的血管張力調控。在大鼠清醒的情況下,先測量兩品系的收縮壓數值,以確定SHR已具有高血壓。大鼠犧牲之後,取下胸主動脈做血管張力實驗,在有無PVAT incubated solution的情況下去觀察其血管反應性以及內皮功能的表現,之後再合併給予不同抑制劑去觀察PVAT incubated solution的作用是否能被抑制。剩餘的胸主動脈與乙醯膽鹼 (acetylcholine, ACh)或PVAT incubated solution反應5到15分鐘後,收集反應的溶液來做為NO、6-Keto 前列腺素1α (PGI2的穩定代謝物)和血栓素B2 (血栓素A2的穩定代謝物)濃度的分析。而反應過後的胸主動脈則會存放在-80°C以備日後eNOS、Cav-1和RhoA的蛋白質表現量之分析。RhoA與Cav-1和eNOS與Cav-1之間連結的關係則使用免疫螢光顯微鏡的技術來判斷。
結果:結果顯示給予PVAT incubated solution後,Wistar胸主動脈血管呈現對phenylephrine收縮反應增強以及ACh內皮依賴性舒張反應抑制的現象,若是去除內皮、給予內皮非依賴性舒張劑硝普納 (sodium nitroprusside, SNP)或NOS抑制劑Nω-Nitro-L-arginine methyl ester hydrochloride則PVAT incubated solution的抑制作用會消失,因此,我們推測PVAT 釋出因子可能會抑制內皮NO的生成。之後觀察eNOS、p-eNOSThr495、p-eNOSSer1177、AMPK和Cav-1等與eNOS或其活性調節相關的因子的表現,結果發現只有Cav-1在PVAT incubated solution刺激下有顯著增加的情形,而且也可發現NO在此時顯著地被抑制。實驗觀察PVAT incubated solution對WKY以及SHR胸主動脈血管張力的影響,結果發現WKY與Wistar的結果類似,但在SHR胸主動脈中,高濃度ACh (10 μM)導致血管收縮的情形可被PVAT incubated solution所抑制,由於此一收縮是PGI2活化TP receptor所造成,因此我們進一步觀察PVAT incubated solution對 TP receptor下游訊息傳遞路徑的影響。結果顯示Cav-1與TP receptor下游的RohA有co-localization的現象,而PVAT incubated solution增加胸主動脈Cav-1以及抑制ROK-2 (C-20)的表現,因此,我們推測在SHR胸主動脈中PVAT釋出因子透過增加Cav-1去抑制高濃度ACh (10 μM)活化TP receptor下游RohA/ROK訊息傳遞路徑所產生的血管收縮現象。
結論:PVAT的旁泌素功能在正常血壓或高血壓的大鼠中可能會透過Cav-1調控eNOS或TP receptor下游RohA/ROK訊息傳遞路徑,進而調控血管張力。
Introduction: Adipokines, released from perivascular adipose tissue (PVAT), regulating vascular tone in a paracrine role have been established for several years. In some previous studies, PVAT inhibits endothelial nitric oxide synthase
(eNOS)-derived nitric oxide (NO) production. Endothelial dysfunction is one of the characteristics of hypertension. Comparing to normotensive rats, the genetic model of spontaneously hypertensive rats (SHR) exhibits downregulated caveolin-1 (Cav-1), a eNOS modulator, expression in aortas. Furthermore, the release of endothelium-derived contracting factors (EDCF), like prostacyclin (PGI2), is thought to be the main attribution of endothelial dysfunction in SHR via thromboxane A2 receptor (TP receptor). The activation of TP receptor recruits Ras homolog gene family member A (RhoA)/Rho-associated kinase (ROK) to the plasma membrane of smooth muscle and induces calcium sensitization. Cav-1 is probably implicated in RhoA/ROK pathway, because of colocalization of Cav-1 with RhoA in mice aortas. Cav-1 not only plays a main role in regulation of vascular tone, but also modulates eNOS function as PVAT does. Therefore, effects of PVAT in vascular tone regulation in hypertension were examined.
Materials and methods: Isometric tension studies in isolated thoracic aortas from Wistar (200 to 300 g) rats in the absence or presence of PVAT incubated solution were carried out to examine the vascular reactivity and endothelial function. After administration of several inhibitors, the effects of PVAT incubated solution were observed in the absence or presence of the PVAT. The protein expression of NO regulators, including eNOS, phosphorylated-eNOSThr495 (p-eNOSThr495), p-eNOSSer1177, AMPK, and Cav-1 and the NO production in aortic homogenates were also examined. Furthermore, thoracic aortas from animal model of hypertension, SHR (12-week old), and its comparable normotensive rats, Wistar-Kyoto (WKY, 12-week old), were used to study the effects of PVAT releasing factors. Systolic blood pressure was determined in conscious restrained rats by tail-cuff system in these two species. For NO, 6-Keto prostaglandin F1α (6-Keto PGF1α, a stable hydrolyzed product of unstable PGI2), and thromboxane B2 (TxB2, a stable metabolites of thromboxane A2 (TxA2)) measurements, aortas were incubated with or without ACh or PVAT incubation for 5 to 15 min, and then the incubation solutions were collected. In addition, the remaining aortic rings were stored at -80°C for eNOS, Cav-1, and RhoA protein detection. Moreover, co-localization of RhoA with Cav-1 and eNOS with Cav-1 were confirmed by immunofluorescence microscopy analysis.
Results: Results demonstrated that PVAT incubated solution enhanced contractile response to phenylephrine and reduced the endothelium-dependent dilatory response to acetylcholine (ACh). After the endothelium was denuded, the administration of endothelium-independent vasodilator sodium nitroprusside or NOS inhibitor Nω-Nitro-L-arginine methyl ester hydrochloride, the inhibitory effect of PVAT incubated solution was diminished. According to the results, we suggest that PVAT releasing factors plays an inhibitory role in endothelial NO production. We also observed eNOS and its activity by measuring the protein expression of eNOS, p-eNOSThr495, p-eNOSSer1177, AMPK, and Cav-1. We found that PVAT releasing factors significantly increased the protein expression of aortic Cav-1; Meanwhile, the aortic NO production was inhibited significantly. We further performed the PVAT effects on aortic rings from WKY and SHR. The results from WKY were similar to those from Wistar. Interestingly, the vasoconstriction induced by high concentration of ACh (10 μM) in SHR aortas was disappeared after PVAT treatment. Because activation of TP receptor is known to be involved in the high concentration of ACh (10 μM)-induced vasoconstriction in SHR aortas, we further investigated the effects of PVAT on TP receptor signal pathway. The co-localization of RhoA (the downstream factor of TP receptor signal pathway) with Cav-1 indicated that Cav-1 is interacted with RhoA. As shown in our previous study, PVAT releasing factors also enhanced aortic Cav-1 and reduced ROK-2 (C-20) protein expressions in SHR. The enhancement of Cav-1 protein expression by PVAT releasing factors could inhibit the high concentration of ACh (10 μM) induced vasoconstriction via regulation of TP receptor RhoA/ROK signal pathway.
Conclusions: The paracrine roles of PVAT involve in regulation of blood pressure through Cav-1, which modulates eNOS or TP receptor RhoA/ROK signal pathway, in normal and hypertensive rats.
正文目錄……………………………………………………………...I
圖表目錄…………………………………………………………….IV
Abbreviations………………………………………………………...X
中文摘要…………………………………………………………..XIII
Abstract…………………………………………………………...XVII
第一章 緒言…………………………………………………………..1
第一節、脂肪組織可釋出脂肪細胞激素 (adipokine)………………………1
第二節、PVAT的paracrine作用能夠影響血管張力……………………...2
第三節、eNOS活性的調控…………………………………………………5
第四節、Cav-1對eNOS的調控………………………………………...….5
第五節、高血壓的動物模式………………………………………………...7
第六節、高血壓之機轉:內皮功能受損…………………………………...8
第七節、在SHR中內皮受損的主因與前列腺環素 (prostacyclin, PGI2)之
關係……………………………………………………………….10
第八節、TP receptor下游RhoA/RhoA-associated kinase (ROK)訊息傳遞路
徑與SHR血壓調控的關係係…...………………………………..12
第九節、RhoA與Cav-1之間的關係………………………………………..13
第十節、實驗目的………………………………………………………….14
第二章 材料與方法…………………………………………………15
第一節、材料……………………………………………………………….15
第二節、實驗動物福祉…………………………………………………….16
第三節、實驗動物………………………………………………………….16
第四節、血壓的測定……………………………………………………….17
第五節、胸主動脈血管環的製備………………………………………….17
第六節、胸主動脈血管反應性…………………………………………….18
第七節、胸主動脈均質物 (homogenate)和培養溶液 (condition medium)的
製備…………………………………………………………….…19
第八節、西方墨點法 (Western blotting)分析……………………………...19
第九節、NO 的測定………………………………………………………..20
第十節、6-Keto PGF1α和TxB2的測定……………………………………20
第十一節、免疫螢光染色分析…………………………………………….21
第十二節、數據分析……………………………………………………….21
第三章 結果…………………………………………………………22
第一節、PVAT釋出因子透過增加Cav-1的表現抑制正常血壓大鼠胸主
動脈內皮功能……………………………..……………………..22
壹、PVAT condition medium對血管收縮張力的影響…………….…..22
貳、 PVAT condition medium對胸主動脈內皮功能的影響…………...22
參、內皮調節因子對PVAT condition medium增加血管收縮張力的貢
獻…………………………………………………………………….23
肆、PVAT condition medium對eNOS蛋白質表現量和活性的影響....24
伍、Cav-1在 PVAT condition medium增加血管收縮張力中所扮演的角
色…………………………………………………………………….24
第二節、PVAT condition medium透過增加Cav-1表現抑制高血壓大鼠胸
主動脈血管收縮 張力………………...………………………….25
壹、SHR的SBP和胸主動脈PE的張力反應…………………...…….25
貳、NO、eNOS和Cav-1在SHR胸主動脈中的表現………………...26
參、COX與SHR胸主動脈內皮受損有關……………………………..27
肆、TP receptor與SHR胸主動脈內皮受損有關………………………..28
伍、PGI2造成WKY和SHR胸主動脈的收縮與活化TP receptor訊息傳遞
路徑有關……………………………………………………...……..29
陸、Cav-1與活化TP receptor的訊息傳遞路徑有關……………………30
柒、NO的表現量與TP receptor的訊息傳遞路徑的活化有關…………31
捌、PVAT造成WKY和SHR胸主動脈呈現抗舒張反應是內皮依賴性的,
並與TP recpetor的訊息傳遞路徑有關……………………………...31
玖、Cav-1與eNOS之間的關係………………………………………….32
拾、PVAT condition medium對Cav-1、eNOS和NO表現量的影響與機
轉…………………………………………………………………….33
第四章 討論…………………………………………………………34
第一節、在正常血壓大鼠中PVAT condition medium對其胸主動脈的影響
…………………………………………………………………….34
壹、 PVAT condition medium對血管張力的調控:不同血管以及不同實驗方法的影響…………………………………………………...34
貳、PVAT釋出因子對血管內皮功能的調控…….……………...……...37
參、PVAT釋出因子對eNOS活性的調控……………………………….38
肆、PVAT 釋出因子透過Cav-1影響血管內皮功能…………………..39
第二節、在高血壓大鼠中PVAT釋出因子對其胸主動脈的影響………...40
壹、PGI2對血管張力的調控:不同年齡以及不同血壓的影響……….40
貳、在高血壓的情況下NO負回饋機制對Cav-1的調控……………….41
參、PGI2在正常血壓以及高血壓情況下的作用機轉………………….42
肆、TP receptor在正常血壓以及高血壓情況下的作用機轉…………..44
伍、RhoA、Cav-1和eNOS在正常血壓以及高血壓情況下對血管張力的
作用………………………………………………………………….45
第五章 結論…………………………………………………………49
第六章 未來展望……………………………………………………50
參考文獻…………………………………………………………….51
Amano M, Fukata Y, Kaibuchi K (2000) Regulation and functions of Rho-associated kinase. Exp Cell Res 261:44-51.
Amano M, Chihara K, Nakamura N, Kaneko T, Matsuura Y, Kaibuchi K (1999) The COOH terminus of Rho-kinase negatively regulates rho-kinase activity. J Biol Chem 274:32418-32424.
Arita H, Nakano T, Hanasaki K (1989) Thromboxane A2: its generation and role in platelet activation. Prog Lipid Res 28:273-301.
Armstrong RA, Wilson NH (1995) Aspects of the thromboxane receptor system. Gen Pharmacol 26:463-472.
Auch-Schwelk W, Katusic ZS, Vanhoutte PM (1990) Thromboxane A2 receptor antagonists inhibit endothelium-dependent contractions. Hypertension 15:699-703.
Bell DR (1993) Vascular smooth muscle responses to endothelial autacoids in rats with chronic coarctation hypertension. J Hypertens 11:65-74.
Blair A, Shaul PW, Yuhanna IS, Conrad PA, Smart EJ (1999) Oxidized low density lipoprotein displaces endothelial nitric-oxide synthase (eNOS) from plasmalemmal caveolae and impairs eNOS activation. J Biol Chem 274:32512-32519.
Boegehold MA (1993) Enhanced arteriolar vasomotion in rats with chronic salt-induced hypertension. Microvasc Res 45:83-94.
Boulanger CM, Morrison KJ, Vanhoutte PM (1994) Mediation by M3-muscarinic receptors of both endothelium-dependent contraction and relaxation to acetylcholine in the aorta of the spontaneously hypertensive rat. Br J Pharmacol 112:519-524.
Brasier AR, Li J, Wimbish KA (1996) Tumor necrosis factor activates angiotensinogen gene expression by the Rel A transactivator. Hypertension 27:1009-1017.
Brun RP, Kim JB, Hu E, Altiok S, Spiegelman BM (1996) Adipocyte differentiation: a transcriptional regulatory cascade. Curr Opin Cell Biol 8:826-832.
Calver A, Collier J, Moncada S, Vallance P (1992) Effect of local intra-arterial NG-monomethyl-L-arginine in patients with hypertension: the nitric oxide dilator mechanism appears abnormal. J Hypertens 10:1025-1031.
Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277-359.
Chen C, Jiang J, Lü JM, Chai H, Wang X, Lin PH, Yao Q (2010) Resistin decreases expression of endothelial nitric oxide synthase through oxidative stress in human coronary artery endothelial cells. Am J Physiol Heart Circ Physiol 299:H193-201.
Cogolludo A, Moreno L, Bosca L, Tamargo J, Perez-Vizcaino F (2003) Thromboxane A2-induced inhibition of voltage-gated K+ channels and pulmonary vasoconstriction: role of protein kinase Czeta. Circ Res 93:656-663.
Danaei G, Finucane MM, Lin JK, Singh GM, Paciorek CJ, Cowan MJ, Farzadfar F, Stevens GA, Lim SS, Riley LM, Ezzati M, Pressure) GBoMRFoCDCGB (2011) National, regional, and global trends in systolic blood pressure since 1980: systematic analysis of health examination surveys and epidemiological studies with 786 country-years and 5·4 million participants. Lancet 377:568-577.
De Mey JG, Vanhoutte PM (1982) Heterogeneous behavior of the canine arterial and venous wall. Importance of the endothelium. Circ Res 51:439-447.
De Mey JG, Vanhoutte PM (1983) Anoxia and endothelium-dependent reactivity of the canine femoral artery. J Physiol 335:65-74.
Deliconstantinos G, Villiotou V, Stavrides JC (1995) Modulation of particulate nitric oxide synthase activity and peroxynitrite synthesis in cholesterol enriched endothelial cell membranes. Biochem Pharmacol 49:1589-1600.
Denniss SG, Jeffery AJ, Rush JW (2010) RhoA-Rho kinase signaling mediates endothelium- and endoperoxide-dependent contractile activities characteristic of hypertensive vascular dysfunction. Am J Physiol Heart Circ Physiol 298:H1391-1405.
DeWitt DL, el-Harith EA, Smith WL (1989) Molecular cloning of prostaglandin G/H synthase. Adv Prostaglandin Thromboxane Leukot Res 19:454-457.
Doggrell SA, Brown L (1998) Rat models of hypertension, cardiac hypertrophy and failure. Cardiovasc Res 39:89-105.
Dubrovska G, Verlohren S, Luft FC, Gollasch M (2004) Mechanisms of ADRF release from rat aortic adventitial adipose tissue. Am J Physiol Heart Circ Physiol 286:H1107-1113.
Engelmann GL, Vitullo JC, Gerrity RG (1987) Morphometric analysis of cardiac hypertrophy during development, maturation, and senescence in spontaneously hypertensive rats. Circ Res 60:487-494.
Fang L, Zhao J, Chen Y, Ma T, Xu G, Tang C, Liu X, Geng B (2009) Hydrogen sulfide derived from periadventitial adipose tissue is a vasodilator. J Hypertens 27:2174-2185.
Feng J, Ito M, Ichikawa K, Isaka N, Nishikawa M, Hartshorne DJ, Nakano T (1999) Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle myosin phosphatase. J Biol Chem 274:37385-37390.
Feron O, Dessy C, Moniotte S, Desager JP, Balligand JL (1999) Hypercholesterolemia decreases nitric oxide production by promoting the interaction of caveolin and endothelial nitric oxide synthase. J Clin Invest 103:897-905.
Flavahan NA, Vanhoutte PM (1990) G-proteins and endothelial responses. Blood Vessels 27:218-229.
Fortuño A, Rodríguez A, Gómez-Ambrosi J, Muñiz P, Salvador J, Díez J, Frühbeck G (2002) Leptin inhibits angiotensin II-induced intracellular calcium increase and vasoconstriction in the rat aorta. Endocrinology 143:3555-3560.
Franklin SS, Jacobs MJ, Wong ND, L'Italien GJ, Lapuerta P (2001) Predominance of isolated systolic hypertension among middle-aged and elderly US hypertensives: analysis based on National Health and Nutrition Examination Survey (NHANES) III. Hypertension 37:869-874.
Frühbeck G (1999) Pivotal role of nitric oxide in the control of blood pressure after leptin administration. Diabetes 48:903-908.
Fujimoto S, Dohi Y, Aoki K, Asano M, Matsuda T (1987) Diminished beta-adrenoceptor-mediated relaxation of arteries from spontaneously hypertensive rats before and during development of hypertension. Eur J Pharmacol 136:179-187.
Funk CD, Funk LB, Kennedy ME, Pong AS, Fitzgerald GA (1991) Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment. FASEB J 5:2304-2312.
Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373-376.
Furchgott RF, Vanhoutte PM (1989) Endothelium-derived relaxing and contracting factors. FASEB J 3:2007-2018.
Fésüs G, Dubrovska G, Gorzelniak K, Kluge R, Huang Y, Luft FC, Gollasch M (2007) Adiponectin is a novel humoral vasodilator. Cardiovasc Res 75:719-727.
Gao YJ (2007) Dual modulation of vascular function by perivascular adipose tissue and its potential correlation with adiposity/lipoatrophy-related vascular dysfunction. Curr Pharm Des 13:2185-2192.
Gao YJ, Lu C, Su LY, Sharma AM, Lee RM (2007) Modulation of vascular function by perivascular adipose tissue: the role of endothelium and hydrogen peroxide. Br J Pharmacol 151:323-331.
Gao YJ, Takemori K, Su LY, An WS, Lu C, Sharma AM, Lee RM (2006) Perivascular adipose tissue promotes vasoconstriction: the role of superoxide anion. Cardiovasc Res 71:363-373.
Gentile MT, Vecchione C, Marino G, Aretini A, Di Pardo A, Antenucci G, Maffei A, Cifelli G, Iorio L, Landolfi A, Frati G, Lembo G (2008) Resistin impairs insulin-evoked vasodilation. Diabetes 57:577-583.
Gluais P, Lonchampt M, Morrow JD, Vanhoutte PM, Feletou M (2005) Acetylcholine-induced endothelium-dependent contractions in the SHR aorta: the Janus face of prostacyclin. Br J Pharmacol 146:834-845.
Gomez E, Schwendemann C, Roger S, Simonet S, Paysant J, Courchay C, Verbeuren TJ, Félétou M (2008) Aging and prostacyclin responses in aorta and platelets from WKY and SHR rats. Am J Physiol Heart Circ Physiol 295:H2198-2211.
Gomez-Mendikute A, Etxeberria A, Olabarrieta I, Cajaraville MP (2002) Oxygen radicals production and actin filament disruption in bivalve haemocytes treated with benzo(a)pyrene. Mar Environ Res 54:431-436.
Greenstein AS, Khavandi K, Withers SB, Sonoyama K, Clancy O, Jeziorska M, Laing I, Yates AP, Pemberton PW, Malik RA, Heagerty AM (2009) Local inflammation and hypoxia abolish the protective anticontractile properties of perivascular fat in obese patients. Circulation 119:1661-1670.
Hailstones D, Sleer LS, Parton RG, Stanley KK (1998) Regulation of caveolin and caveolae by cholesterol in MDCK cells. J Lipid Res 39:369-379.
Halushka PV, Mais DE, Mayeux PR, Morinelli TA (1989) Thromboxane, prostaglandin and leukotriene receptors. Annu Rev Pharmacol Toxicol 29:213-239.
Himpens B, Kitazawa T, Somlyo AP (1990) Agonist-dependent modulation of Ca2+ sensitivity in rabbit pulmonary artery smooth muscle. Pflugers Arch 417:21-28.
Iacobellis G, Gao YJ, Sharma AM (2008) Do cardiac and perivascular adipose tissue play a role in atherosclerosis? Curr Diab Rep 8:20-24.
Ishizaki T, Maekawa M, Fujisawa K, Okawa K, Iwamatsu A, Fujita A, Watanabe N, Saito Y, Kakizuka A, Morii N, Narumiya S (1996) The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase. EMBO J 15:1885-1893.
Janssen LJ, Lu-Chao H, Netherton S (2001) Excitation-contraction coupling in pulmonary vascular smooth muscle involves tyrosine kinase and Rho kinase. Am J Physiol Lung Cell Mol Physiol 280:L666-674.
Japp AG, Newby DE (2008) The apelin-APJ system in heart failure: pathophysiologic relevance and therapeutic potential. Biochem Pharmacol 75:1882-1892.
Japp AG, Cruden NL, Amer DA, Li VK, Goudie EB, Johnston NR, Sharma S, Neilson I, Webb DJ, Megson IL, Flapan AD, Newby DE (2008) Vascular effects of apelin in vivo in man. J Am Coll Cardiol 52:908-913.
Johns DG, Webb RC (1998) TNF-alpha-induced endothelium-independent vasodilation: a role for phospholipase A2-dependent ceramide signaling. Am J Physiol 275:H1592-1598.
Katugampola SD, Maguire JJ, Matthewson SR, Davenport AP (2001) [(125)I]-(Pyr(1))Apelin-13 is a novel radioligand for localizing the APJ orphan receptor in human and rat tissues with evidence for a vasoconstrictor role in man. Br J Pharmacol 132:1255-1260.
Knudsen HL, Frangos JA (1997) Role of cytoskeleton in shear stress-induced endothelial nitric oxide production. Am J Physiol 273:H347-355.
Konishi M, Su C (1983) Role of endothelium in dilator responses of spontaneously hypertensive rat arteries. Hypertension 5:881-886.
Krause BR, Hartman AD (1984) Adipose tissue and cholesterol metabolism. J Lipid Res 25:97-110.
Laufs U, La Fata V, Plutzky J, Liao JK (1998) Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 97:1129-1135.
Laufs U, Endres M, Stagliano N, Amin-Hanjani S, Chui DS, Yang SX, Simoncini T, Yamada M, Rabkin E, Allen PG, Huang PL, Böhm M, Schoen FJ, Moskowitz MA, Liao JK (2000) Neuroprotection mediated by changes in the endothelial actin cytoskeleton. J Clin Invest 106:15-24.
Lee YC, Chang HH, Chiang CL, Liu CH, Yeh JI, Chen MF, Chen PY, Kuo JS, Lee TJ (2011) Role of perivascular adipose tissue-derived methyl palmitate in vascular tone regulation and pathogenesis of hypertension. Circulation 124:1160-1171.
Legrand MC, Benessiano J, Levy BI (1993) Endothelium, mechanical compliance, and cGMP content in the carotid artery from spontaneously hypertensive rats. J Cardiovasc Pharmacol 21 Suppl 1:S26-30.
Lembo G, Vecchione C, Fratta L, Marino G, Trimarco V, d'Amati G, Trimarco B (2000) Leptin induces direct vasodilation through distinct endothelial mechanisms. Diabetes 49:293-297.
Levy JV (1980) Prostacyclin-induced contraction of isolated aortic strips from normal and spontaneously hypertensive rats (SHR). Prostaglandins 19:517-525.
Li R, Andersen I, Aleke J, Golubinskaya V, Gustafsson H, Nilsson H (2013) Reduced anti-contractile effect of perivascular adipose tissue on mesenteric small arteries from spontaneously hypertensive rats: role of Kv7 channels. Eur J Pharmacol 698:310-315.
Lim SS et al. (2012) A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380:2224-2260.
Linder L, Kiowski W, Bühler FR, Lüscher TF (1990) Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. Circulation 81:1762-1767.
Lyons D, Webster J, Benjamin N (1994) The effect of antihypertensive therapy on responsiveness to local intra-arterial NG-monomethyl-L-arginine in patients with essential hypertension. J Hypertens 12:1047-1052.
Löhn M, Dubrovska G, Lauterbach B, Luft FC, Gollasch M, Sharma AM (2002) Periadventitial fat releases a vascular relaxing factor. FASEB J 16:1057-1063.
Lüscher TF, Vanhoutte PM (1986) Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. Hypertension 8:344-348.
Lüscher TF, Raij L, Vanhoutte PM (1987) Endothelium-dependent vascular responses in normotensive and hypertensive Dahl rats. Hypertension 9:157-163.
Lüscher TF, Aarhus LL, Vanhoutte PM (1990) Indomethacin improves the impaired endothelium-dependent relaxations in small mesenteric arteries of the spontaneously hypertensive rat. Am J Hypertens 3:55-58.
Maenhaut N, Van de Voorde J (2011) Regulation of vascular tone by adipocytes. BMC Med 9:25.
Mancia G et al. (2014) 2013 ESH/ESC Practice Guidelines for the Management of Arterial Hypertension. Blood Press 23:3-16.
Marchesi C, Ebrahimian T, Angulo O, Paradis P, Schiffrin EL (2009) Endothelial nitric oxide synthase uncoupling and perivascular adipose oxidative stress and inflammation contribute to vascular dysfunction in a rodent model of metabolic syndrome. Hypertension 54:1384-1392.
Masuzawa K, Matsuda T, Asano M (1989) Decreased arterial responsiveness to multiple cyclic AMP-generating receptor agonists in spontaneously hypertensive rats. Br J Pharmacol 96:227-235.
Matsuda K, Teragawa H, Fukuda Y, Nakagawa K, Higashi Y, Chayama K (2003) Leptin causes nitric-oxide independent coronary artery vasodilation in humans. Hypertens Res 26:147-152.
Matsui T, Amano M, Yamamoto T, Chihara K, Nakafuku M, Ito M, Nakano T, Okawa K, Iwamatsu A, Kaibuchi K (1996) Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO J 15:2208-2216.
Meijer RI, Bakker W, Alta CL, Sipkema P, Yudkin JS, Viollet B, Richter EA, Smulders YM, van Hinsbergh VW, Serné EH, Eringa EC (2013) Perivascular adipose tissue control of insulin-induced vasoreactivity in muscle is impaired in db/db mice. Diabetes 62:590-598.
Minghini A, Britt LD, Hill MA (1998) Interleukin-1 and interleukin-6 mediated skeletal muscle arteriolar vasodilation: in vitro versus in vivo studies. Shock 9:210-215.
Mohamed-Ali V, Pinkney JH, Coppack SW (1998) Adipose tissue as an endocrine and paracrine organ. Int J Obes Relat Metab Disord 22:1145-1158.
Momin AU, Melikian N, Shah AM, Grieve DJ, Wheatcroft SB, John L, El Gamel A, Desai JB, Nelson T, Driver C, Sherwood RA, Kearney MT (2006) Leptin is an endothelial-independent vasodilator in humans with coronary artery disease: Evidence for tissue specificity of leptin resistance. Eur Heart J 27:2294-2299.
Moncada S, Palmer RM, Higgs EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109-142.
Mount PF, Kemp BE, Power DA (2007) Regulation of endothelial and myocardial NO synthesis by multi-site eNOS phosphorylation. J Mol Cell Cardiol 42:271-279.
Mukai Y, Sato S (2009) Polyphenol-containing azuki bean (Vigna angularis) extract attenuates blood pressure elevation and modulates nitric oxide synthase and caveolin-1 expressions in rats with hypertension. Nutr Metab Cardiovasc Dis 19:491-497.
Mulvany MJ, Halpern W (1976) Mechanical properties of vascular smooth muscle cells in situ. Nature 260:617-619.
Noma K, Oyama N, Liao JK (2006) Physiological role of ROCKs in the cardiovascular system. Am J Physiol Cell Physiol 290:C661-668.
Nuno DW, England SK, Lamping KG (2012) RhoA localization with caveolin-1 regulates vascular contractions to serotonin. Am J Physiol Regul Integr Comp Physiol 303:R959-967.
Ohkawa F, Ikeda U, Kawasaki K, Kusano E, Igarashi M, Shimada K (1994) Inhibitory effect of interleukin-6 on vascular smooth muscle contraction. Am J Physiol 266:H898-902.
Okamoto K, Aoki K (1963) Development of a strain of spontaneously hypertensive rats. Jpn Circ J 27:282-293.
Owen MK, Witzmann FA, McKenney ML, Lai X, Berwick ZC, Moberly SP, Alloosh M, Sturek M, Tune JD (2013) Perivascular adipose tissue potentiates contraction of coronary vascular smooth muscle: influence of obesity. Circulation 128:9-18.
Panza JA, Quyyumi AA, Brush JE, Epstein SE (1990) Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 323:22-27.
Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA (1993) Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation 87:1468-1474.
Pavlides S, Gutierrez-Pajares JL, Danilo C, Lisanti MP, Frank PG (2012) Atherosclerosis, caveolae and caveolin-1. Adv Exp Med Biol 729:127-144.
Payne GA, Bohlen HG, Dincer UD, Borbouse L, Tune JD (2009) Periadventitial adipose tissue impairs coronary endothelial function via PKC-beta-dependent phosphorylation of nitric oxide synthase. Am J Physiol Heart Circ Physiol 297:H460-465.
Payne GA, Borbouse L, Bratz IN, Roell WC, Bohlen HG, Dick GM, Tune JD (2008) Endogenous adipose-derived factors diminish coronary endothelial function via inhibition of nitric oxide synthase. Microcirculation 15:417-426.
Payne GA, Borbouse L, Kumar S, Neeb Z, Alloosh M, Sturek M, Tune JD (2010) Epicardial perivascular adipose-derived leptin exacerbates coronary endothelial dysfunction in metabolic syndrome via a protein kinase C-beta pathway. Arterioscler Thromb Vasc Biol 30:1711-1717.
Pearson PJ, Vanhoutte PM (1993) Vasodilator and vasoconstrictor substances produced by the endothelium. Rev Physiol Biochem Pharmacol 122:1-67.
Rajsheker S, Manka D, Blomkalns AL, Chatterjee TK, Stoll LL, Weintraub NL (2010) Crosstalk between perivascular adipose tissue and blood vessels. Curr Opin Pharmacol 10:191-196.
Rapoport RM, Williams SP (1996) Role of prostaglandins in acetylcholine-induced contraction of aorta from spontaneously hypertensive and Wistar-Kyoto rats. Hypertension 28:64-75.
Razani B, Woodman SE, Lisanti MP (2002) Caveolae: from cell biology to animal physiology. Pharmacol Rev 54:431-467.
Razani B, Engelman JA, Wang XB, Schubert W, Zhang XL, Marks CB, Macaluso F, Russell RG, Li M, Pestell RG, Di Vizio D, Hou H, Jr., Kneitz B, Lagaud G, Christ GJ, Edelmann W, Lisanti MP (2001) Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem 276:38121-38138.
Riento K, Ridley AJ (2003) Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol 4:446-456.
Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801-809.
Rubanyi GM, Vanhoutte PM (1985) Hypoxia releases a vasoconstrictor substance from the canine vascular endothelium. J Physiol 364:45-56.
Salcedo A, Garijo J, Monge L, Fernández N, Luis García-Villalón A, Sánchez Turrión V, Cuervas-Mons V, Diéguez G (2007) Apelin effects in human splanchnic arteries. Role of nitric oxide and prostanoids. Regul Pept 144:50-55.
Sawada Y, Sakamaki T, Nakamura T, Sato K, Ono Z, Murata K (1994) Release of nitric oxide in response to acetylcholine is unaltered in spontaneously hypertensive rats. J Hypertens 12:745-750.
Schrader LI, Kinzenbaw DA, Johnson AW, Faraci FM, Didion SP (2007) IL-6 deficiency protects against angiotensin II induced endothelial dysfunction and hypertrophy. Arterioscler Thromb Vasc Biol 27:2576-2581.
Scotland RS, Chauhan S, Vallance PJ, Ahluwalia A (2001) An endothelium-derived hyperpolarizing factor-like factor moderates myogenic constriction of mesenteric resistance arteries in the absence of endothelial nitric oxide synthase-derived nitric oxide. Hypertension 38:833-839.
Sessa WC (2004) eNOS at a glance. J Cell Sci 117:2427-2429.
Shimokawa H, Yasutake H, Fujii K, Owada MK, Nakaike R, Fukumoto Y, Takayanagi T, Nagao T, Egashira K, Fujishima M, Takeshita A (1996) The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation. J Cardiovasc Pharmacol 28:703-711.
Smith TL, Hutchins PM (1979) Central hemodynamics in the developmental stage of spontaneous hypertension in the unanesthetized rat. Hypertension 1:508-517.
Soltis EE, Cassis LA (1991) Influence of perivascular adipose tissue on rat aortic smooth muscle responsiveness. Clin Exp Hypertens A 13:277-296.
Somlyo AP, Somlyo AV (2000) Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J Physiol 522 Pt 2:177-185.
Sundström J, Arima H, Jackson R, Turnbull F, Rahimi K, Chalmers J, Woodward M, Neal B, Collaboration BPLTT (2015) Effects of blood pressure reduction in mild hypertension: a systematic review and meta-analysis. Ann Intern Med 162:184-191.
Swärd K, Mita M, Wilson DP, Deng JT, Susnjar M, Walsh MP (2003) The role of RhoA and Rho-associated kinase in vascular smooth muscle contraction. Curr Hypertens Rep 5:66-72.
Sánchez M, Galisteo M, Vera R, Villar IC, Zarzuelo A, Tamargo J, Pérez-Vizcaíno F, Duarte J (2006) Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats. J Hypertens 24:75-84.
Taddei S, Virdis A, Mattei P, Salvetti A (1993) Vasodilation to acetylcholine in primary and secondary forms of human hypertension. Hypertension 21:929-933.
Taguchi R, Takasu J, Itani Y, Yamamoto R, Yokoyama K, Watanabe S, Masuda Y (2001) Pericardial fat accumulation in men as a risk factor for coronary artery disease. Atherosclerosis 157:203-209.
Tosun M, Paul RJ, Rapoport RM (1998) Role of extracellular Ca++ influx via L-type and non-L-type Ca++ channels in thromboxane A2 receptor-mediated contraction in rat aorta. J Pharmacol Exp Ther 284:921-928.
Trayhurn P, Wood IS (2004) Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92:347-355.
Trippodo NC, Frohlich ED (1981) Similarities of genetic (spontaneous) hypertension. Man and rat. Circ Res 48:309-319.
Tuncer M, Vanhoutte PM (1993) Response to the endothelium-dependent vasodilator acetylcholine in perfused kidneys of normotensive and spontaneously hypertensive rats. Blood Press 2:217-220.
Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T, Tamakawa H, Yamagami K, Inui J, Maekawa M, Narumiya S (1997) Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389:990-994.
Vanhoutte PM (1987a) Endothelium and responsiveness of vascular smooth muscle. J Hypertens Suppl 5:S115-120.
Vanhoutte PM (1987b) Endothelium-dependent contractions in arteries and veins. Blood Vessels 24:141-144.
Vanhoutte PM (1988) The endothelium--modulator of vascular smooth-muscle tone. N Engl J Med 319:512-513.
Vanhoutte PM (1989) Endothelium and control of vascular function. State of the Art lecture. Hypertension 13:658-667.
Vanhoutte PM (1990) Endothelium-derived relaxing and contracting factors. Adv Nephrol Necker Hosp 19:3-16.
Vanhoutte PM (1997) Endothelial dysfunction and atherosclerosis. Eur Heart J 18 Suppl E:E19-29.
Vanhoutte PM, Shimokawa H (1989) Endothelium-derived relaxing factor and coronary vasospasm. Circulation 80:1-9.
Vanhoutte PM, Scott-Burden T (1994) The endothelium in health and disease. Tex Heart Inst J 21:62-67.
Vanhoutte PM, Boulanger CM (1995) Endothelium-dependent responses in hypertension. Hypertens Res 18:87-98.
Vanhoutte PM, Shimokawa H, Tang EH, Feletou M (2009) Endothelial dysfunction and vascular disease. Acta Physiol (Oxf) 196:193-222.
Vaziri ND, Wang XQ (1999) cGMP-mediated negative-feedback regulation of endothelial nitric oxide synthase expression by nitric oxide. Hypertension 34:1237-1241.
Vecchione C, Maffei A, Colella S, Aretini A, Poulet R, Frati G, Gentile MT, Fratta L, Trimarco V, Trimarco B, Lembo G (2002) Leptin effect on endothelial nitric oxide is mediated through Akt-endothelial nitric oxide synthase phosphorylation pathway. Diabetes 51:168-173.
Velasco G, Armstrong C, Morrice N, Frame S, Cohen P (2002) Phosphorylation of the regulatory subunit of smooth muscle protein phosphatase 1M at Thr850 induces its dissociation from myosin. FEBS Lett 527:101-104.
Vera R, Sánchez M, Galisteo M, Villar IC, Jimenez R, Zarzuelo A, Pérez-Vizcaíno F, Duarte J (2007) Chronic administration of genistein improves endothelial dysfunction in spontaneously hypertensive rats: involvement of eNOS, caveolin and calmodulin expression and NADPH oxidase activity. Clin Sci (Lond) 112:183-191.
Verhagen SN, Visseren FL (2011) Perivascular adipose tissue as a cause of atherosclerosis. Atherosclerosis 214:3-10.
Vidal F, Colomé C, Martínez-González J, Badimon L (1998) Atherogenic concentrations of native low-density lipoproteins down-regulate nitric-oxide-synthase mRNA and protein levels in endothelial cells. Eur J Biochem 252:378-384.
Wang P, Xu TY, Guan YF, Su DF, Fan GR, Miao CY (2009) Perivascular adipose tissue-derived visfatin is a vascular smooth muscle cell growth factor: role of nicotinamide mononucleotide. Cardiovasc Res 81:370-380.
Williams SP, Dorn GW, Rapoport RM (1994) Prostaglandin I2 mediates contraction and relaxation of vascular smooth muscle. Am J Physiol 267:H796-803.
Wilson DP, Susnjar M, Kiss E, Sutherland C, Walsh MP (2005) Thromboxane A2-induced contraction of rat caudal arterial smooth muscle involves activation of Ca2+ entry and Ca2+ sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697. Biochem J 389:763-774.
Wise H, Jones RL (1996) Focus on prostacyclin and its novel mimetics. Trends Pharmacol Sci 17:17-21.
Wort SJ, Ito M, Chou PC, Mc Master SK, Badiger R, Jazrawi E, de Souza P, Evans TW, Mitchell JA, Pinhu L, Ito K, Adcock IM (2009) Synergistic induction of endothelin-1 by tumor necrosis factor alpha and interferon gamma is due to enhanced NF-kappaB binding and histone acetylation at specific kappaB sites. J Biol Chem 284:24297-24305.
Wozniak SE, Gee LL, Wachtel MS, Frezza EE (2009) Adipose tissue: the new endocrine organ? A review article. Dig Dis Sci 54:1847-1856.
Xi W, Satoh H, Kase H, Suzuki K, Hattori Y (2005) Stimulated HSP90 binding to eNOS and activation of the PI3-Akt pathway contribute to globular adiponectin-induced NO production: vasorelaxation in response to globular adiponectin. Biochem Biophys Res Commun 332:200-205.
Yamamoto M, Marui N, Sakai T, Morii N, Kozaki S, Ikai K, Imamura S, Narumiya S (1993) ADP-ribosylation of the rhoA gene product by botulinum C3 exoenzyme causes Swiss 3T3 cells to accumulate in the G1 phase of the cell cycle. Oncogene 8:1449-1455.
Yamawaki H, Hara N, Okada M, Hara Y (2009) Visfatin causes endothelium-dependent relaxation in isolated blood vessels. Biochem Biophys Res Commun 383:503-508.
Yamawaki H, Tsubaki N, Mukohda M, Okada M, Hara Y (2010) Omentin, a novel adipokine, induces vasodilation in rat isolated blood vessels. Biochem Biophys Res Commun 393:668-672.
Zavaritskaya O, Zhuravleva N, Schleifenbaum J, Gloe T, Devermann L, Kluge R, Mladenov M, Frey M, Gagov H, Fésüs G, Gollasch M, Schubert R (2013) Role of KCNQ channels in skeletal muscle arteries and periadventitial vascular dysfunction. Hypertension 61:151-159.
Zhang C, Hein TW, Wang W, Kuo L (2003) Divergent roles of angiotensin II AT1 and AT2 receptors in modulating coronary microvascular function. Circ Res 92:322-329.
Zhang DX, Yi FX, Zou AP, Li PL (2002) Role of ceramide in TNF-alpha-induced impairment of endothelium-dependent vasorelaxation in coronary arteries. Am J Physiol Heart Circ Physiol 283:H1785-1794.
Zhao YJ, Wang J, Tod ML, Rubin LJ, Yuan XJ (1996) Pulmonary vasoconstrictor effects of prostacyclin in rats: potential role of thromboxane receptors. J Appl Physiol (1985) 81:2595-2603.
Zhu Y, Liao HL, Wang N, Yuan Y, Ma KS, Verna L, Stemerman MB (2000) Lipoprotein promotes caveolin-1 and Ras translocation to caveolae: role of cholesterol in endothelial signaling. Arterioscler Thromb Vasc Biol 20:2465-2470.
Zhu Y, Liao HL, Niu XL, Yuan Y, Lin T, Verna L, Stemerman MB (2003) Low density lipoprotein induces eNOS translocation to membrane caveolae: the role of RhoA activation and stress fiber formation. Biochim Biophys Acta 1635:117-126.
Zicha J, Kunes J (1999) Ontogenetic aspects of hypertension development: analysis in the rat. Physiol Rev 79:1227-1282.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊