壓力負(fù)荷增加大鼠模型血漿內(nèi)皮素水平的改變

1、壓力負(fù)荷增加大鼠模型血漿內(nèi)皮素水平的改變    摘要 目的:觀察壓力負(fù)荷增加對(duì)大鼠血漿內(nèi)皮素水平的影響。方法:采用腹主動(dòng)脈狹窄法所致壓力負(fù)荷增加誘發(fā)大鼠左室肥厚模型,觀察左室重量指數(shù)(LVMI),采用放射免疫分析法檢測(cè)血漿內(nèi)皮素水平。結(jié)果:LVMI模型組明顯高于假手術(shù)組(P<0.01);血漿內(nèi)皮素水平模型組較假手術(shù)組顯著升高(P<0.01)。結(jié)論:腹主動(dòng)脈縮窄所致壓力負(fù)荷增加可誘發(fā)大鼠左室肥厚,該作用可能與血漿內(nèi)皮素水平升高有關(guān)。 關(guān)鍵詞 慢性心力衰竭; 壓力負(fù)荷; 內(nèi)皮素; 大鼠 Changes of the plasma endothel

2、in in rats with pressure overloadAbstract Objective: To observe the effects of pressure overload on level of plasma endothelin, and study the possible mechanism of left ventricular remodeling. Methods: left ventricular mass index(LVMI) and plasma endothelin were measured in the rat models with myoca

3、rdial hypertrophy of chronic heart failure and pressure overload by abdominal aortic constriction by radioimmunoassay. Results: LVMI in the model group was obviously higher than that of the sham group(P<0.01). The plasma endothelin levels in the model group were obviously higher than those of sha

4、m group(P<0.01). Conclusion: pressure overload by abdominal aortic constriction can induce left ventricular remodeling in chronic heart failure, the mechanism of left ventricular remodeling might be related to the upregulated endothelin levels in plasma. Key words chronic heart failure; pressure

5、overload; endothelin; rats 心室重塑是導(dǎo)致心力衰竭(heart failure,HF)不斷進(jìn)展的病理生理學(xué)基礎(chǔ),HF時(shí)心室重塑的病理刺激主要來(lái)自兩方面:一方面神經(jīng)內(nèi)分泌的過(guò)度激活,另一方面為血流動(dòng)力學(xué)異常。研究發(fā)現(xiàn),異常升高的血管緊張素(Ang)、去甲腎上腺素(NE)、醛固酮和內(nèi)皮素(ET)等可直接作用于心肌,促進(jìn)心肌肥厚、心肌細(xì)胞凋亡和間質(zhì)纖維化1。ET是目前已知最強(qiáng)烈持久的血管收縮因子,不但直接刺激或激活多種激素和細(xì)胞因子,而且參與心血管疾病的病理生理過(guò)程2。作者通過(guò)觀察壓力負(fù)荷增加對(duì)大鼠血漿ET水平的影響,以探討血漿ET在HF病理生理過(guò)程中的作用。 1 材料和方

6、法 1.1 實(shí)驗(yàn)材料 動(dòng)物:雄性SD大鼠20只,體重180200 g;血漿ET放免藥盒(解放軍總醫(yī)院科技開發(fā)中心放射免疫所提供)。1.2 方法 1.2.1 造模方法 參考Doering等3的方法,2%戊巴比妥鈉40 mgkg-1腹腔注射麻醉,固定,剃毛,常規(guī)消毒,分層打開腹腔,在左腎上緣分開后腹膜等軟組織暴露腹主動(dòng)脈,并在雙腎動(dòng)脈上方分離腹主動(dòng)脈,用銀夾造成腹主動(dòng)脈狹窄(銀夾內(nèi)徑0.7 mm),分層關(guān)閉腹腔。 1.2.2 實(shí)驗(yàn)分組 所有動(dòng)物隨機(jī)分為模型組和假手術(shù)組2組,均常規(guī)喂養(yǎng)。假手術(shù)組手術(shù)時(shí)只分離腹主動(dòng)脈,不用銀夾縮窄,余操作與模型組相同。手術(shù)8周后處死,計(jì)算左室重量指數(shù)(LVMI),利用

7、光鏡觀察左室心肌病理形態(tài)。 1.3 觀察指標(biāo) 1.3.1 LVMI 左室與室間隔的重量(濕重)為左室重量,用上海精科天平廠生產(chǎn)的JA1003型電子天平稱重。左室重量(mg)/體重(g)為L(zhǎng)VMI()。 1.3.2 左室心肌病理形態(tài) 常規(guī)石蠟切片采用HE染色,經(jīng)過(guò)脫蠟、染色、脫水、二甲苯透明及中性樹膠封固等步驟,在光鏡下觀察4。 1.3.3 血漿ET放免測(cè)定 腹主動(dòng)脈取血2 ml,注入含10% EDTA二鈉30 l和抑肽酶40 l的試管中,混勻,4 3 000 rmin-1離心10 min,分離血漿。-70 存放,測(cè)定前冷水中復(fù)融,再次4 3 000 rmin-1離心5 min,取上清采用非平衡

8、法測(cè)定5。將聚苯乙稀試管編號(hào),經(jīng)過(guò)加液程序后4 3 500 rmin-1離心25 min,吸棄上清液,在計(jì)數(shù)器上測(cè)定沉淀cpm數(shù)。 1.4 統(tǒng)計(jì)學(xué)處理 定量資料以±s表示,用SPSS 11.5統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)學(xué)處理。模型組和假手術(shù)組之間比較采用t檢驗(yàn),P<0.05表示差異有統(tǒng)計(jì)學(xué)意義。 2 結(jié)果 2.1 LVMI 壓力負(fù)荷增加大鼠造模8周LVMI模型組(2.98±0.36)較假手術(shù)組(2.11±0.14)有顯著升高(P<0.05)。 2.2 左室心肌HE染色結(jié)果 光鏡下假手術(shù)組造模8周后左室心肌HE染色顯示:心肌纖維排列整齊,心肌細(xì)胞大小正常;模型組造

9、模8周后左室心肌HE染色發(fā)現(xiàn):心肌纖維排列紊亂,細(xì)胞橫徑稍大(圖1、2)。 2.3 血漿ET水平的改變 壓力負(fù)荷增加大鼠各組血漿ET水平的改變見圖3,模型組血漿ET水平較假手術(shù)組顯著升高(P<0.01)。 3 討論 ET是一族由血管內(nèi)皮細(xì)胞、心肌、平滑肌等合成及分泌的含21個(gè)氨基酸的活性多肽,是目前已知最強(qiáng)烈持久的血管收縮因子,可使所有的動(dòng)、靜脈強(qiáng)烈收縮,其強(qiáng)度比Ang強(qiáng)10倍,比NE強(qiáng)1 000倍,尤其是對(duì)冠狀動(dòng)脈的作用最強(qiáng);另ET-1還具有刺激心肌細(xì)胞增生肥大和促進(jìn)心臟纖維化等生物學(xué)效應(yīng)6。生理?xiàng)l件下,低濃度的ET對(duì)維持血管張力和血壓具有重要意義;在某些病理?xiàng)l件下,ET則過(guò)量釋放7。

10、如慢性心力衰竭(CHF)時(shí)心輸出量下降,心室壁機(jī)械負(fù)荷過(guò)重,導(dǎo)致組織切應(yīng)力改變,心肌受損部位周圍神經(jīng)內(nèi)分泌激活和組織缺氧可使心肌細(xì)胞ET-1過(guò)度表達(dá),不僅引起血管痙攣、心肌纖維化和心肌平滑肌細(xì)胞裂解與凋亡,同時(shí)可直接刺激或激活多種激素和細(xì)胞因子,共同參與CHF的病理生理過(guò)程8。 ET的釋放受許多因素的調(diào)節(jié),如缺氧、機(jī)械性應(yīng)力、神經(jīng)內(nèi)分泌激素(如NE、Ang)、細(xì)胞因子(包括轉(zhuǎn)化生長(zhǎng)因子-和白介素-1)等均可誘導(dǎo)ET-1的表達(dá)。HF時(shí),血中ET-1水平明顯升高,升高的程度與HF的嚴(yán)重程度呈正相關(guān)關(guān)系。隨著年齡的增長(zhǎng),血漿ET-1活性水平隨之上升,而有氧鍛煉可降低血漿ET-1的活性9。最近研究發(fā)現(xiàn)

11、,特異性ET-1基因敲除大鼠心肌細(xì)胞的凋亡增加,而ET-1可通過(guò)FasL/TNF信號(hào)通路削弱TNF介導(dǎo)的凋亡10。Khan等11的實(shí)驗(yàn)認(rèn)為big-ET是進(jìn)展期HF患者的獨(dú)立預(yù)后因素;還有一些學(xué)者提出了不同意見,但大多數(shù)研究者已達(dá)成共識(shí),認(rèn)為ET-1是HF強(qiáng)烈的獨(dú)立預(yù)后因素12。本研究通過(guò)腹主動(dòng)脈縮窄法制作的大鼠模型,造模8周后LVMI模型組較假手術(shù)組有顯著升高(P<0.01);模型組左室心肌經(jīng)HE染色光鏡下見心肌纖維排列紊亂,細(xì)胞橫徑稍大,循環(huán)ET水平升高。 由于ET在心血管系統(tǒng)中舉足輕重的作用,近年來(lái)對(duì)ET的認(rèn)識(shí)也逐漸深刻。研究發(fā)現(xiàn)ET-1即ETA和ETB對(duì)心臟的作用主要通過(guò)內(nèi)皮素受體

12、(endothelin receptor,ETR)介導(dǎo),其中以ETA為主。人類ETA受體mRNA主要表達(dá)于血管平滑肌細(xì)胞,ETB受體mRNA大量表達(dá)于血管內(nèi)皮細(xì)胞,也表達(dá)于主動(dòng)脈、肺動(dòng)脈和冠狀動(dòng)脈的血管平滑肌細(xì)胞。ETA受體選擇性與ET-1結(jié)合,而ETB受體與ET的各種異構(gòu)體均具有相同的親和力,也稱為非特異性受體13。由于ETR的分布具有組織特異性,所以它們發(fā)揮的功能也不盡相同,ETA受體主要介導(dǎo)心血管收縮作用,ETB受體通過(guò)釋放舒張因子,如前列環(huán)素(PGI2)、一氧化氮(NO)而介導(dǎo)心血管舒張作用,ETB受體還有清除循環(huán)ET-1作用。最近研究發(fā)現(xiàn),ET-1和ETR結(jié)合后通過(guò)一系列過(guò)程可激活促

13、分裂原活化蛋白激酶(MAPK),使細(xì)胞生長(zhǎng)、肥大,參與心肌重塑。而ET拮抗劑在慢性心力衰竭中的研究觀察到波生坦可減輕HF病人的臨床癥狀14。由于ET和ETB受體結(jié)合后可起到擴(kuò)血管、增加NO和PGI2濃度、增強(qiáng)肺清除ETA等作用,所以選擇性ETA受體拮抗劑可能比同時(shí)抑制ETA和ETB受體的拮抗劑更為有利15。 本實(shí)驗(yàn)運(yùn)用光鏡觀察左室心肌HE染色結(jié)果,同時(shí)檢測(cè)LVMI、血漿ET水平的改變,證實(shí)腹主動(dòng)脈縮窄8周后大鼠心肌肥厚模型建立成功,符合針對(duì)CHF的病理生理改變的要求,為臨床及基礎(chǔ)研究提供新的思路。 參考文獻(xiàn) 1 VON-LUEDER T G, KJEKSHUS H, EDVARDSEN T,

14、et al. Mechanisms of elevated plasma endothelin-1 in CHF: congestion increases pulmonary synthesis and secretion of endothelin-1J. Cardiovasc Res,2004,63(1):41-50. 2 YAMAMOTO S, MATSUMOTO N, KANAZAWA M, et al. Different contributions of endothelin-A and endothelin-B receptors in postischemic cardiac

15、 dysfunction and norepinephrine overflow in rat hearts J. Circulation,2005,111(3):302-309. 3 DOERING C W, JALIL J E, JANICKI J S, et al. Collagen network remodeling and diastolic stiffness of the rat left ventricle with pressure overload hypertrophyJ. Cardiovasc Res,1998,22:686-694. 4 HIGASHIYAMA H,

16、 SUGAI M, INOUE H, et al. Histopathological study of time course changes in inter-renal aortic banding-induced left ventricular hypertrophy of miceJ. Int J Exp Path, 2007,88(1):31-38. 5 BREDIN F, FRANCO-CERECEDA A. Reversed remodeling in dilated cardiomyopathy by passive containment surgery is assoc

17、iated with decreased circulating levels of endothelin-1J. Eur J Cardiothoracic Surg,2006,29(3):299-303. 6 CLOZEL M, SALLOUKH H. Role of endothelin in fibrosis and antifibrotic potential of bosentanJ. Ann Med,2005,37:2-12. 7 肖繼明,陳銳華,徐軍,等.急性心肌梗死患者血漿內(nèi)皮素的動(dòng)態(tài)變化及意義J.醫(yī)學(xué)研究生學(xué)報(bào),2007,20(3):331-332. 8 SHAH R. En

18、dothelins in health and disease J. Eur J Inter Med,2007,18:272-282. 9 van GUILDER G P, WESTBY C M, GREINER J J, et al. Endothelin-1 vasoconstrictor tone increases with age in healthy men but can be reduced by regular aerobic exerciseJ. Hypertension,2007,50:403-409. 10 ZHAO X S, PAN W T, BEKEREDJIAN

19、R, et al. Endogenous endothelin-1 is required for cardiomyocyte survival in vivoJ. Circulation,2006,114:830-837. 11 KHAN S Q, DHILLON O, STRUCK J, et al. C-terminal pro-endothelin-1 offers additional prognostic information in patients after acute myocardial infarction: leicester acute myocardial inf

20、arction peptide(LAMP) studyJ.Am Heart J,2007,154:736-742. 12 YIP H K, WU C J, CHANG H W, et al. Prognostic value of circulating levels of endothelin-1 in patients after acute myocardial infarction undergoing primary coronary angioplastyJ. Chest,2005,127:1491-1497. 13 LAFLAMME K, ROBERGE C J, GERMAIN

21、 L, et al. Tissue-engineered human vascular media with a functional endothelin systemJ. Circulation,2005,111(4):459-464. 14 PACKER M, McMURRAY J, MASSIE B M, et al. Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot stud

22、yJ. J Card Fail,2005,11(1):12-20. 15 COWBURNA P J, CLELANDB J G F, McDONAGH T A, et al. Comparison of selective ETA and ETB receptor antagonists in patients with chronic heart failureJ. Eur J Heart Fail,2005,7:37-42. 參考文獻(xiàn) 1 VON-LUEDER T G, KJEKSHUS H, EDVARDSEN T, et al. Mechanisms of elevated plasm

23、a endothelin-1 in CHF: congestion increases pulmonary synthesis and secretion of endothelin-1J. Cardiovasc Res,2004,63(1):41-50. 2 YAMAMOTO S, MATSUMOTO N, KANAZAWA M, et al. Different contributions of endothelin-A and endothelin-B receptors in postischemic cardiac dysfunction and norepinephrine ove

24、rflow in rat hearts J. Circulation,2005,111(3):302-309. 3 DOERING C W, JALIL J E, JANICKI J S, et al. Collagen network remodeling and diastolic stiffness of the rat left ventricle with pressure overload hypertrophyJ. Cardiovasc Res,1998,22:686-694. 4 HIGASHIYAMA H, SUGAI M, INOUE H, et al. Histopath

25、ological study of time course changes in inter-renal aortic banding-induced left ventricular hypertrophy of miceJ. Int J Exp Path, 2007,88(1):31-38. 5 BREDIN F, FRANCO-CERECEDA A. Reversed remodeling in dilated cardiomyopathy by passive containment surgery is associated with decreased circulating le

26、vels of endothelin-1J. Eur J Cardiothoracic Surg,2006,29(3):299-303. 6 CLOZEL M, SALLOUKH H. Role of endothelin in fibrosis and antifibrotic potential of bosentanJ. Ann Med,2005,37:2-12. 7 肖繼明,陳銳華,徐軍,等.急性心肌梗死患者血漿內(nèi)皮素的動(dòng)態(tài)變化及意義J.醫(yī)學(xué)研究生學(xué)報(bào),2007,20(3):331-332. 8 SHAH R. Endothelins in health and disease J.

27、Eur J Inter Med,2007,18:272-282. 9 van GUILDER G P, WESTBY C M, GREINER J J, et al. Endothelin-1 vasoconstrictor tone increases with age in healthy men but can be reduced by regular aerobic exerciseJ. Hypertension,2007,50:403-409. 10 ZHAO X S, PAN W T, BEKEREDJIAN R, et al. Endogenous endothelin-1 i

28、s required for cardiomyocyte survival in vivoJ. Circulation,2006,114:830-837. 11 KHAN S Q, DHILLON O, STRUCK J, et al. C-terminal pro-endothelin-1 offers additional prognostic information in patients after acute myocardial infarction: leicester acute myocardial infarction peptide(LAMP) studyJ.Am Hea

29、rt J,2007,154:736-742. 12 YIP H K, WU C J, CHANG H W, et al. Prognostic value of circulating levels of endothelin-1 in patients after acute myocardial infarction undergoing primary coronary angioplastyJ. Chest,2005,127:1491-1497. 13 LAFLAMME K, ROBERGE C J, GERMAIN L, et al. Tissue-engineered human

30、vascular media with a functional endothelin systemJ. Circulation,2005,111(4):459-464. 14 PACKER M, McMURRAY J, MASSIE B M, et al. Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot studyJ. J Card Fail,2005,11(1):12-20. 1

31、5 COWBURNA P J, CLELANDB J G F, McDONAGH T A, et al. Comparison of selective ETA and ETB receptor antagonists in patients with chronic heart failureJ. Eur J Heart Fail,2005,7:37-42. 參考文獻(xiàn) 1 VON-LUEDER T G, KJEKSHUS H, EDVARDSEN T, et al. Mechanisms of elevated plasma endothelin-1 in CHF: congestion i

32、ncreases pulmonary synthesis and secretion of endothelin-1J. Cardiovasc Res,2004,63(1):41-50. 2 YAMAMOTO S, MATSUMOTO N, KANAZAWA M, et al. Different contributions of endothelin-A and endothelin-B receptors in postischemic cardiac dysfunction and norepinephrine overflow in rat hearts J. Circulation,

33、2005,111(3):302-309. 3 DOERING C W, JALIL J E, JANICKI J S, et al. Collagen network remodeling and diastolic stiffness of the rat left ventricle with pressure overload hypertrophyJ. Cardiovasc Res,1998,22:686-694. 4 HIGASHIYAMA H, SUGAI M, INOUE H, et al. Histopathological study of time course chang

34、es in inter-renal aortic banding-induced left ventricular hypertrophy of miceJ. Int J Exp Path, 2007,88(1):31-38. 5 BREDIN F, FRANCO-CERECEDA A. Reversed remodeling in dilated cardiomyopathy by passive containment surgery is associated with decreased circulating levels of endothelin-1J. Eur J Cardio

35、thoracic Surg,2006,29(3):299-303. 6 CLOZEL M, SALLOUKH H. Role of endothelin in fibrosis and antifibrotic potential of bosentanJ. Ann Med,2005,37:2-12. 7 肖繼明,陳銳華,徐軍,等.急性心肌梗死患者血漿內(nèi)皮素的動(dòng)態(tài)變化及意義J.醫(yī)學(xué)研究生學(xué)報(bào),2007,20(3):331-332. 8 SHAH R. Endothelins in health and disease J. Eur J Inter Med,2007,18:272-282. 9

36、van GUILDER G P, WESTBY C M, GREINER J J, et al. Endothelin-1 vasoconstrictor tone increases with age in healthy men but can be reduced by regular aerobic exerciseJ. Hypertension,2007,50:403-409. 10 ZHAO X S, PAN W T, BEKEREDJIAN R, et al. Endogenous endothelin-1 is required for cardiomyocyte surviv

37、al in vivoJ. Circulation,2006,114:830-837. 11 KHAN S Q, DHILLON O, STRUCK J, et al. C-terminal pro-endothelin-1 offers additional prognostic information in patients after acute myocardial infarction: leicester acute myocardial infarction peptide(LAMP) studyJ.Am Heart J,2007,154:736-742. 12 YIP H K,

38、WU C J, CHANG H W, et al. Prognostic value of circulating levels of endothelin-1 in patients after acute myocardial infarction undergoing primary coronary angioplastyJ. Chest,2005,127:1491-1497. 13 LAFLAMME K, ROBERGE C J, GERMAIN L, et al. Tissue-engineered human vascular media with a functional en

39、dothelin systemJ. Circulation,2005,111(4):459-464. 14 PACKER M, McMURRAY J, MASSIE B M, et al. Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot studyJ. J Card Fail,2005,11(1):12-20. 15 COWBURNA P J, CLELANDB J G F, McD

40、ONAGH T A, et al. Comparison of selective ETA and ETB receptor antagonists in patients with chronic heart failureJ. Eur J Heart Fail,2005,7:37-42. 參考文獻(xiàn) 1 VON-LUEDER T G, KJEKSHUS H, EDVARDSEN T, et al. Mechanisms of elevated plasma endothelin-1 in CHF: congestion increases pulmonary synthesis and se

41、cretion of endothelin-1J. Cardiovasc Res,2004,63(1):41-50. 2 YAMAMOTO S, MATSUMOTO N, KANAZAWA M, et al. Different contributions of endothelin-A and endothelin-B receptors in postischemic cardiac dysfunction and norepinephrine overflow in rat hearts J. Circulation,2005,111(3):302-309. 3 DOERING C W,

42、 JALIL J E, JANICKI J S, et al. Collagen network remodeling and diastolic stiffness of the rat left ventricle with pressure overload hypertrophyJ. Cardiovasc Res,1998,22:686-694. 4 HIGASHIYAMA H, SUGAI M, INOUE H, et al. Histopathological study of time course changes in inter-renal aortic banding-in

43、duced left ventricular hypertrophy of miceJ. Int J Exp Path, 2007,88(1):31-38. 5 BREDIN F, FRANCO-CERECEDA A. Reversed remodeling in dilated cardiomyopathy by passive containment surgery is associated with decreased circulating levels of endothelin-1J. Eur J Cardiothoracic Surg,2006,29(3):299-303. 6

44、 CLOZEL M, SALLOUKH H. Role of endothelin in fibrosis and antifibrotic potential of bosentanJ. Ann Med,2005,37:2-12. 7 肖繼明,陳銳華,徐軍,等.急性心肌梗死患者血漿內(nèi)皮素的動(dòng)態(tài)變化及意義J.醫(yī)學(xué)研究生學(xué)報(bào),2007,20(3):331-332. 8 SHAH R. Endothelins in health and disease J. Eur J Inter Med,2007,18:272-282. 9 van GUILDER G P, WESTBY C M, GREINE

45、R J J, et al. Endothelin-1 vasoconstrictor tone increases with age in healthy men but can be reduced by regular aerobic exerciseJ. Hypertension,2007,50:403-409. 10 ZHAO X S, PAN W T, BEKEREDJIAN R, et al. Endogenous endothelin-1 is required for cardiomyocyte survival in vivoJ. Circulation,2006,114:8

46、30-837. 11 KHAN S Q, DHILLON O, STRUCK J, et al. C-terminal pro-endothelin-1 offers additional prognostic information in patients after acute myocardial infarction: leicester acute myocardial infarction peptide(LAMP) studyJ.Am Heart J,2007,154:736-742. 12 YIP H K, WU C J, CHANG H W, et al. Prognosti

47、c value of circulating levels of endothelin-1 in patients after acute myocardial infarction undergoing primary coronary angioplastyJ. Chest,2005,127:1491-1497. 13 LAFLAMME K, ROBERGE C J, GERMAIN L, et al. Tissue-engineered human vascular media with a functional endothelin systemJ. Circulation,2005,

48、111(4):459-464. 14 PACKER M, McMURRAY J, MASSIE B M, et al. Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot studyJ. J Card Fail,2005,11(1):12-20. 15 COWBURNA P J, CLELANDB J G F, McDONAGH T A, et al. Comparison of sel

49、ective ETA and ETB receptor antagonists in patients with chronic heart failureJ. Eur J Heart Fail,2005,7:37-42. 參考文獻(xiàn) 1 VON-LUEDER T G, KJEKSHUS H, EDVARDSEN T, et al. Mechanisms of elevated plasma endothelin-1 in CHF: congestion increases pulmonary synthesis and secretion of endothelin-1J. Cardiovas

50、c Res,2004,63(1):41-50. 2 YAMAMOTO S, MATSUMOTO N, KANAZAWA M, et al. Different contributions of endothelin-A and endothelin-B receptors in postischemic cardiac dysfunction and norepinephrine overflow in rat hearts J. Circulation,2005,111(3):302-309. 3 DOERING C W, JALIL J E, JANICKI J S, et al. Col

51、lagen network remodeling and diastolic stiffness of the rat left ventricle with pressure overload hypertrophyJ. Cardiovasc Res,1998,22:686-694. 4 HIGASHIYAMA H, SUGAI M, INOUE H, et al. Histopathological study of time course changes in inter-renal aortic banding-induced left ventricular hypertrophy of miceJ. Int J Exp Path, 2007,88(1):31-38. 5 BREDIN F, FRANCO-CERECEDA A. Reversed remodeling in dilated cardiomyopathy by passive containment surgery is assoc