Top

Published in:

01-07-2010 | Original Contribution

Impact of acute myocardial ischemia reperfusion on the tissue and blood-borne renin–angiotensin system

Authors: Shizu Oyamada, Cesario Bianchi, Shinji Takai, Michael P. Robich, Richard T. Clements, Louis Chu, Frank W. Sellke

Published in: Basic Research in Cardiology | Issue 4/2010

Abstract

We examined the impact of acute myocardial ischemia followed by reperfusion (AMI-R) on local and circulating renin–angiotensin system (RAS) in a swine model. The mid left anterior descending artery (n = 6) was occluded for 1 h, followed by reperfusion for 2 h. Monastryl blue/triphenyl tetrazolium chloride staining identified the area-at-risk (AAR) and infarction. A second group of control animals underwent sham operations (C: n = 4). Myocardial expression of angiotensinogen (AGT), renin, chymase, angiotensin converting enzyme (ACE), angiotensin II (Ang II), Ang II type1 receptor (AT1R) and Ang II type 2 receptor (AT2R) in the AAR and the non-ischemic left ventricle (NLV) was assessed. Serum level of these proteins at baseline and at the end of reperfusion was also examined. Chymase (P < 0.05), ACE (P < 0.05), Ang II (P < 0.05), AT1R (P < 0.05) and AT2R (P < 0.05) expressions were found to be significantly higher in the AAR compared to the NLV and C whereas no significant differences were found for AGT (P = 0.58) and renin (P = 0.38). Serum concentration of ACE was significantly higher at the end of reperfusion than at baseline (P < 0.01), whereas no significant difference was found for chymase (P = 0.71), AGT (P = 0.57) and Ang II (P = 0.19). Immunohistochemistry of myocardial sections demonstrated significantly higher expression of ACE (P = 0.02), AT1R (P = 0.01), AT2R (P = 0.02) and Ang II (P < 0.01) in the AAR as compared to the NLV, whereas no significant difference was found for renin (P = 0.39). In conclusion, AMI-R resulted in significantly higher expression of specific cardiac RAS components in AAR compared to the NLV in the acute period.

Amedeo Modesti P, Zecchi-Orlandini S, Vanni S, Polidori G, Bertolozzi I, Perna AM, Formigli L, Cecioni I, Coppo M, Boddi M, Serneri GG (2002) Release of preformed Ang II from myocytes mediates angiotensinogen and ET-1 gene overexpression in vivo via AT1 receptor. J Mol Cell Cardiol 34:1491–1500CrossRefPubMed

Bafford R, Sui XX, Wang G, Conte M (2006) Angiotensin II and tumor necrosis factor-alpha upregulate survivin and Kruppel-like factor 5 in smooth muscle cells: potential relevance to vein graft hyperplasia. Surgery 140:289–296CrossRefPubMed

Beil WJ, Schulz M, McEuen AR, Buckley MG, Walls AF (1997) Number, fixation properties, dye-binding and protease expression of duodenal mast cells: comparisons between healthy subjects and patients with gastritis or Crohn’s disease. Histochem J 29:759–773CrossRefPubMed

Caughey GH, Raymond WW, Wolters PJ (2000) Angiotensin II generation by mast cell alpha-and beta-chymases. Biochim Biophys Acta 1480

Cerbai E, Crucitti A, Sartiani L, De Paoli P, Pino R, Rodriguez ML, Gensini G, Mugelli A (2000) Long-term treatment of spontaneously hypertensive rats with losartan and electrophysiological remodeling of cardiac myocytes. Cardiovasc Res 45:388–396CrossRefPubMed

Cohn JN, Tognoni G (2001) Valsartan heart failure trial investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 345:1667–1675CrossRefPubMed

Cristovam PC, Arnoni CP, de Andrade MC, Casarini DE, Pereira LG, Schor N, Boim MA (2008) ACE-dependent and chymase-dependent angiotensin II generation in normal and glucose-stimulated human mesangial cells. Exp Biol Med 233:1035–1043CrossRef

Dahlhof B (2001) Left ventricular hypertrophy and angiotensin II antagonists. Am J Hypert 14:174–182CrossRef

Dell’Italia LJ, Husain A (2002) Dissecting the role of chymase in angiotensin II formation and heart and blood vessel diseases. Curr Opin Cardiol 17:374–379CrossRefPubMed

10.

Diniz GP, Carneiro-Ramos MS, Barreto-Chaves MLM (2009) Angiotensin type 1 receptor mediates thyroid hormone-induced cardiomyocyte hypertrophy through the Akt/GSK-3β/mTOR signaling pathway. Basic Res Cardiol 104:653–667CrossRefPubMed

11.

du Toit EF, Nabben M, Lochner A (2005) A potential role for angiotensin II in obesity induced cardiac hypertrophy and ischemic/reperfusion injury. Basic Res Cardiol 100:346–354CrossRefPubMed

12.

Endo-Mochizuki Y, Mochizuki N, Sawa H, Takada A, Okamoto H, Kawaguchi H, Nagashima K, Kitabatake A (1995) Expression of renin and angiotensin-converting enzyme in human hearts. Heart Vessels 10:285–293CrossRefPubMed

13.

Engels W, Reiters PH, Daemen MJ, Smits JF, van der Vusse GJ (1995) Transmural changes in mast cell density in rat heart after infarct induction in vivo. J Pathol 177:423–429CrossRefPubMed

14.

Ertl G, Alexander RW, Kloner RA (1983) Interactions between coronary occlusion and renin–angiotensin system in the dog. Basic Res Cardiol 78:518–533CrossRefPubMed

15.

Ertl G, Kloner RA, Alexander RW, Braunwald E (1982) Limitation of experimental infarct size by angiotensin-converting enzyme inhibitor. Circulation 65:40–48PubMed

16.

Ertl G, Meesmann M, Kochsiek K (1985) On the mechanism of renin release during experimental myocardial ischemia. Eur J Clin Invest 15:375–381CrossRefPubMed

17.

Fulton GJ, Davies MG, Barber L, Svendsen E, Hagen PO (1998) Localized versus systemic angiotensin II receptor inhibition of intimal hyperplasia in experimental vein grafts by the specific angiotensin II receptor inhibitor L158, 809. Surgery 123:218–227PubMed

18.

Ichihara S, Senbonmatsu T, Price E, Ichiki T, Graffney A, Inagami T (2002) Targeted deletion of angiotensin II type 2 receptor caused cardiac rupture after acute myocardial infarction. Circulation 106:2244–2249CrossRefPubMed

19.

Jalowy A, Schulz R, Dörge H, Behrends M, Heusch G (1998) Infarct size reduction by AT1-receptor blockade through a signal cascade of AT2-receptor activation, bradykinin and prostaglandins in pigs. J Am Coll Cardiol 32:1787–1796CrossRefPubMed

20.

Jin D, Takai S, Yamada M, Sakaguchi M, Kamoshita K, Ishida K, Sukenaga Y, Miyazaki M (2003) Impact of chymase inhibitor on cardiac function and survival after myocardial infarction. Cardiovasc Res 60:413–420CrossRefPubMed

21.

Jin D, Takai S, Yamada M, Sakaguchi M, Yao Y, Miyazaki M (2001) Possible roles of cardiac chymase after myocardial infarction in hamster hearts. Jpn J Pharmacol 86:203–214CrossRefPubMed

22.

Kagiyama S, Eguchi S, Frank GD, Inagami T, Zhang YC, Phillips I (2002) Angiotensin II-induced cardiac hypertrophy and hypertension are attenuated by epidermal growth factor receptor antisense. Circulation 106:909–912CrossRefPubMed

23.

Keller AW, Clancy RM, Barr ML, Marboe CC, Cannon PJ (1988) Acute reoxygenation injury in the isolated rat heart: role of resident cardiac mast cells. Circ Res 63:1044–1052PubMed

24.

Kirimura K, Takai S, Jin D, Muramatsu M, Kishi K, Yoshikawa K, Nakabayashi M, Mino Y, Miyazaki M (2005) Role of chymase-dependent angiotensin II formation in regulating blood pressure in spontaneously hypertensive rats. Hypertens Res 28:457–464CrossRefPubMed

25.

Kjukshus J, Swedberg K, Snapinn S (1992) Effect of enalapril on long-term mortality in severe congestive heart failure. CONSENSUS Trial Group. Am J Cardiol 69:103–110CrossRef

26.

Koka V, Wang W, Huang XR, Kim-Mitsuyama S, Truong LD, Lan HY (2006) Advanced glycation end products activate a chymase-dependent angiotensin II-generating pathway in diabetic complications. Circulation 113:1353–1360CrossRefPubMed

27.

Kumar R, Baker KM, Pan J (2007) Cardiac and vascular renin–angiotensin systems. In: RM C (ed) Hypertension and hormone mechanisms. Jumana Press, Totowa, NJ, pp 23–42

28.

Kumar R, Boim MA (2009) Diversity of pathways for intracellular angiotensin II synthesis. Curr Opin Nephro Hypertens 18:283–285

29.

Kumar R, Singh VP, Baker KM (2009) The intracellular renin–angiotensin system in the heart. Curr Hypertens Rep 11:104–110CrossRefPubMed

30.

Lagunoff D, Pritzl P (1976) Characterization of rat mast cell granule proteins. Arch Biochem Biophys 173:554–563CrossRefPubMed

31.

Le Trong H, Neurath H, Woodbury RG (1987) Substrate specificity of the chymotrypsin-like protease in secretory granules isolated from rat mast cells. Proc Natl Acas Sci USA 84:364–367CrossRef

32.

Matsumoto C, Hayashi T, Kitada K, Yamashita C, Miyamura M, Mori T, Ukimura A, Ohkita M, Jin D, Takai S, Miyazaki M, Okada Y, Kitaura Y, Matsumura Y (2009) Chymase plays an important role in left ventricular remodeling induced by intermittent hypoxia in mice. Hypertension 54:164–171CrossRefPubMed

33.

Miyazaki M, Takai S (2000) Role of chymase on vascular proliferation. J Renin Angiotensin Aldosterone Syst 1:23–26CrossRefPubMed

34.

Nabah YN, Mateo T, Estellés R, Mata M, Zagorski J, Sarau H, Cortijo J, Morcillo EJ, Jose PJ, Sanz MJ (2004) Angiotensin II induces neutrophil accumulation in vivo through generation and release of CXC chemokines. Circulation 110:3581–3586CrossRefPubMed

35.

Newton CR, Curran B, Victorino GP (2004) Angiotensin II type 1 receptor activation increases microvascular hydraulic permeability. Surgery 136:1054–1060CrossRefPubMed

36.

Okamura A, Rakugi H, Ohishi M, Yanagitani Y, Takiuchi S, Moriguchi K, Fennessy PA, Higaki J, Ogihara T (1999) Upregulation of renin–angiotensin system during differentiation of monocytes to macrophages. J Hypertens 17:537–545CrossRefPubMed

37.

Osipov RM, Bianchi C, Clements RT, Feng J, Liu Y, Xu SH, Robich MP, Wagstaff J, Sellke FW (2009) Thrombin fragment (TP508) decreases myocardial infarction and apoptosis after ischemia reperfusion injury. Ann Thorac Surg 87:786–793CrossRefPubMed

38.

Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S (2003) CHARM Investigators and Committees. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 362:759–766CrossRefPubMed

39.

Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Køber L, Maggioni AP, Solomon SD, Swedberg K, Van de Werf F, White H, Leimberger JD, Henis M, Edwards S, Zelenkofske S, Sellers MA, Califf RM (2003) Valsartan in Acute Myocardial Infarction Trial Investigators. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 349:1893–1906CrossRefPubMed

40.

Preckel B, Schlack W, Gonzalez M, Obal D, Barthel H, Thamer V (2000) Influence of the angiotensin II AT1 receptor antagonist irbesartan on ischemia/reperfusion injury in the dog hear. Basic Res Cardiol 95:404–412CrossRefPubMed

41.

Prossed HCG, Forster ME, Richards AM, Pemberton CJ (2009) Cardiac chymase converts rat proAngiotensin-12 (PA12) to angiotensin II: effects of PA12 upon cardiac haemodynamics. Cardiovasc Res 82:40–50CrossRef

42.

Reilly CF, Tewksbury DA, Schechter NM, Travis J (1982) Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases. J Biol Chem 257:8619–8622PubMed

43.

Ritter O, Schuh K, Brede M, Röthlein N, Burkard N, Hein L, Neyses L (2003) AT2-receptor activation regulates myocardial eNOS expression via the calcineurin-NF-AT pathway. FASEB J 17:283–285PubMed

44.

Rosendorff C (1996) The renin–angiotensin system and vascular hypertrophy. J Am Coll Cardiol 28:803–812CrossRefPubMed

45.

Sayama S, Iozzo RV, Lazarus GS, Schechter NM (1987) Human skin chymotrypsin-like proteinase chym. J Biol Chem 262:6808–6815PubMed

46.

Saygili E, Rana OR, Meyer C, Gemein C, Andrzejewski MG, Ludwig A, Weber C, Schotten U, Krüttgen A, Weis J, Schwinger RH, Mischke K, Rassaf T, Kelm M, Schauerte P (2009) The angiotensin-calcineurin-NFAT pathway mediates stretch-induced up-regulation of matrix metalloproteinases-2/-9 in atrial myocytes. Basic Res Cardiol 104:48–435CrossRef

47.

Singh VP, Le B, Bhat VB, Baker KM, Kumar R (2007) High-glucose-induced regulation of intracellular ANG II synthesis and nuclear redistribution in cardiac myocytes. Am J Physiol Heart Circ Physiol 293:939–948CrossRef

48.

Singh VP, Baker KM, Kumar R (2008) Activation of the intracellular renin–angiotensin system in cardiac fibroblasts by high glucose: role in extracellular matrix production. Am J Physiol Heart Circ Physiol 294:1675–1684CrossRef

49.

Singh VP, Le B, Khode R, Baker KM, Kumar R (2008) Intracellular angiotensin II production in diabetic rats is correlated with cardiomyocyte apoptosis, oxidative stress, and cardiac fibrosis. Diabetes 57:3297–3306CrossRefPubMed

50.

Sodha NR, Clements RT, Feng J, Liu Y, Bianchi C, Horvath EM, Szabo C, Sellke FW (2008) The effects of therapeutic sulfide on myocardial apoptosis in response to ischemia-reperfusion injury. Eur J Cardiothorac Surg 33:906–913CrossRefPubMed

51.

SOLVD (1992) Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. The SOLVD Investigattors. N Engl J Med 327:685–691CrossRef

52.

Takai S, Shiota N, Kobayashi S, Matsumura E, Miyazaki M (1997) Induction of chymase that forms angiotensin II in the monkey atherosclerotic aorta. FEBS Lett 412:86–90CrossRefPubMed

53.

Takai S, Shiota N, Yamamoto D, Okunishi H, Miyazaki M (1996) Purification and characterization of angiotensin II-generating chymase from hamster cheek pouch. Life Sci 58:591–597CrossRefPubMed

54.

Tsai CT, Lai LP, Hwang JJ, Chen WP, Chiang FT, Hsu KL, Tseng CD, Tseng YZ, Lin JL (2008) Renin–angiotensin system component expression in the HL-1 atrial cell line and in a pig model of atrial fibrillation. J Hypertens 26:570–582CrossRefPubMed

55.

Urata H, Boehm KD, Philip A, Kinoshita A, Gabrovsek J, Bumpus FM, Husain A (1993) Cellular localization and regional distribution of an angiotensin II-forming chymase in the heart. J Clin Invest 91:1269–1281CrossRefPubMed

56.

Urata H, Kinoshita A, Misono KS, Bumpus FM, Husain A (1990) Indentification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart. J Biol Chem 265:22348–22357PubMed

57.

Utsunomiya H, Nakamura M, Kakubo K, Inagami T, Tamura M (2005) Angiotensin II AT2 receptor localization in cardiovascular tissues by its antibody developed in AT2 gene-deleted mice. Regul Pept 126:155–161CrossRefPubMed

58.

Weidenbach R, Schulz R, Gres P, Behrends M, Post H, Heusch G (2000) Enhanced reduction of myocardial infarct size by combined ACE inhibition and AT1 receptor antagonism. Br J Pharmacol 131:138–144CrossRefPubMed

59.

Wenzel S, Tastan I, Abdallah Y, Schreckenberg R, Schlüter KD (2009) Aldosterone improves contractile function of adult rat ventricular cardiomyocytes in a non-acute way: potential relationship to the calcium paradox of aldosteronism. Basic Res Cardiol 105:247–256CrossRefPubMed

60.

Yam FK, Akers WS, Ferraris VA, Smith K, Ramaiah C, Camp P, Flynn JD (2006) Interventions to improve guideline compliance following coronary artery bypass grafting. Surgery 140:541–552CrossRefPubMed

61.

Zhu GQ, Zucker IH, Wang W (2002) Central AT1 receptor involved in the enhanced cardiac sympathetic afferent reflex in rats with chronic heart failure. Basic Res Cardiol 97:320–326CrossRefPubMed

Title: Impact of acute myocardial ischemia reperfusion on the tissue and blood-borne renin–angiotensin system
Authors: Shizu Oyamada
Cesario Bianchi
Shinji Takai
Michael P. Robich
Richard T. Clements
Louis Chu
Frank W. Sellke
Publication date: 01-07-2010
Publisher: Springer-Verlag
Published in: Basic Research in Cardiology / Issue 4/2010
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-010-0093-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Impact of acute myocardial ischemia reperfusion on the tissue and blood-borne renin–angiotensin system

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2010

Proatherogenic effects of estradiol in a model of accelerated atherosclerosis in ovariectomized ApoE-deficient mice

C-kit+ CD45− cells found in the adult human heart represent a population of endothelial progenitor cells

CB1 receptor inhibition leads to decreased vascular AT1 receptor expression, inhibition of oxidative stress and improved endothelial function

Direct relationship between levels of TNF-α expression and endothelial dysfunction in reperfusion injury

Kinases and phosphatases in ischaemic preconditioning: a re-evaluation

Long-term protection and mechanism of pacing-induced postconditioning in the heart