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Rat Genomics pp 403-414 | Cite as

Rat Models of Cardiovascular Diseases

  • Michael BaderEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 597)

Abstract

In cardiovascular research, the rat has been the main model of choice for decades. Experimental procedures were developed to generate cardiovascular disease states in this species, such as systemic and pulmonary hypertension, cardiac hypertrophy and failure, myocardial infarction, and stroke. Furthermore, rats have been bred, which spontaneously develop such diseases. They became extremely valuable models to understand the genetics of these diseases, since powerful genomic tools are now available for the rat. One of these tools is transgenic technology, which has allowed the creation of even more disease models in the rat. This review summarizes the experimental, genetic, and transgenic rat models for cardiovascular diseases.

Key words:

Systemic hypertension Pulmonary hypertension Cardiac hypertrophy Heart failure Myocardial infarction Stroke Transgenic rat 

References

  1. 1.
    Aitman TJ, Critser JK, Cuppen E, Dominiczak AF, Fernandez XM, Flint J, Gauguier D, Geurts AM, Gould M, Harris PC, Holmdahl R, Huebner N, Iszvak Z, Jacob H, Kuramoto T, Kwitek AE, Marrone A, Mashimo T, Moreno-Quinn C, Mullins J, Mullins LJ, Olsson T, Riley L, Saar K, Serikawa T, Shul JD, Szpirer C, Twigger SN, Voigt B, Worley K (2008) Progress and prospects in rat genetics: a community view. Nat Genet 40:516–522CrossRefPubMedGoogle Scholar
  2. 2.
    Mullins JJ, Peters J, Ganten D (1990) Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene. Nature 344:541–544CrossRefPubMedGoogle Scholar
  3. 3.
    Hammer RE, Maika SD, Richardson JA, Tang J, Taurog JD (1990) Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human β2m: an animal model of HLA-B27-associated human disorders. Cell 63:1099–1112CrossRefPubMedGoogle Scholar
  4. 4.
    Ganten D, Wagner J, Zeh K, Bader M, Michel J-B, Paul M, Zimmermann F, Ruf P, Hilgenfeldt U, Ganten U, Kaling M, Bachmann S, Fukamizu A, Mullins JJ, Murakami K (1992) Species specificity of renin kinetics in transgenic rats harboring the human renin and angiotensinogen genes. Proc Natl Acad Sci USA 89:7806–7810CrossRefPubMedGoogle Scholar
  5. 5.
    Silva JA Jr, Araujo RC, Baltatu O, Oliveira SM, Tschöpe C, Fink E, Hoffmann S, Plehm R, Chai KX, Chao L, Chao J, Ganten D, Pesquero JB, Bader M (2000) Reduced cardiac hypertrophy and altered blood pressure control in transgenic rats with the human tissue kallikrein gene. FASEB J 14:1858–1860PubMedGoogle Scholar
  6. 6.
    Langenickel T, Buttgereit J, Pagel-Langenickel I, Lindner M, Beuerlein K, Al-Saadi N, Plehm R, Popova E, Tank J, Dietz R, Willenbrock R, Bader M (2006) Cardiac hypertrophy in transgenic rats expressing a dominant negative mutant of the natriuretic peptide receptor B. Proc Natl Acad Sci USA 103:4735–4740CrossRefPubMedGoogle Scholar
  7. 7.
    Bader M, Bohnemeier H, Zollmann FS, Lockley-Jones OE, Ganten D (2000) Transgenic animals in cardiovascular disease research. Exp Physiol 85:713–731CrossRefPubMedGoogle Scholar
  8. 8.
    Buehr M, Meek S, Blair K, Yang J, Ure J, Silva J, McLay R, Hall J, Ying QL, Smith A (2008) Capture of authentic embryonic stem cells from rat blastocysts. Cell 135:1287–1298CrossRefPubMedGoogle Scholar
  9. 9.
    Li P, Tong C, Mehrian-Shai R, Jia L, Wu N, Yan Y, Maxson RE, Schulze EN, Song H, Hsieh CL, Pera MF, Ying QL (2008) Germline competent embryonic stem cells derived from rat blastocysts. Cell 135:1299–1310CrossRefPubMedGoogle Scholar
  10. 10.
    Herold MJ, van den BJ, Seibler J, Reichardt HM (2008) Inducible and reversible gene silencing by stable integration of an shRNA-encoding lentivirus in transgenic rats. Proc Natl Acad Sci U S A 105:18507–18512CrossRefPubMedGoogle Scholar
  11. 11.
    Kotnik K, Popova E, Todiras M, Mori MA, Alenina N, Seibler J, Bader M (2009) Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown. PLoS One 4:e5124Google Scholar
  12. 12.
    Doggrell SA, Brown L (1998) Rat models of hypertension, cardiac hypertrophy and failure. Cardiovasc Res 39:89–105CrossRefPubMedGoogle Scholar
  13. 13.
    Pinto YM, Paul M, Ganten D (1998) Lessons from rat models of hypertension: from Goldblatt to genetic engineering. Cardiovasc Res 39:77–88CrossRefPubMedGoogle Scholar
  14. 14.
    Yagil Y, Yagil C (2001) Genetic models of hypertension in experimental animals. Exp Nephrol 9:1–9CrossRefPubMedGoogle Scholar
  15. 15.
    De Champlain J, Krakoff LR, Axelrod J (1967) Catecholamine metabolism in experimental hypertension in the rat. Circ Res 20:136–145PubMedGoogle Scholar
  16. 16.
    Schenk J, McNeill JH (1992) The pathogenesis of DOCA-salt hypertension. J Pharmacol Toxicol Methods 27:161–170CrossRefPubMedGoogle Scholar
  17. 17.
    Rees DD, Palmer RM, Schulz R, Hodson HF, Moncada S (1990) Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol 101:746–752PubMedGoogle Scholar
  18. 18.
    Johnson RA, Freeman RH (1992) Sustained hypertension in the rat induced by chronic blockade of nitric oxide production. Am J Hypertens 5:919–922PubMedGoogle Scholar
  19. 19.
    Ribeiro MO, Antunes E, de Nucci G, Lovisolo SM, Zatz R (1992) Chronic inhibition of nitric oxide synthesis. A new model of arterial hypertension. Hypertension 20:298–303PubMedGoogle Scholar
  20. 20.
    Campbell DJ (2006) L-NAME hypertension: trying to fit the pieces together. J Hypertens 24:33–36CrossRefPubMedGoogle Scholar
  21. 21.
    Martinez-Maldonado M (1991) Pathophysiology of renovascular hypertension. Hypertension 17:707–719PubMedGoogle Scholar
  22. 22.
    Pickering TG (1989) Renovascular hypertension: etiology and pathophysiology. Semin Nucl Med 19:79–88CrossRefPubMedGoogle Scholar
  23. 23.
    Goldblatt H, Lynch J, Hanzal RF, Summerville WW (1934) The production of persistent elevation of systolic blood pressure by means of renal ischemia. J Exp Med 59:347–379CrossRefPubMedGoogle Scholar
  24. 24.
    Dickinson CJ, Lawrence JR (1963) A slowly developing pressor response to small concentrations of angiotensin. Its bearing on the pathogenesis of chronic renal hypertension. Lancet 1:1354–1356CrossRefPubMedGoogle Scholar
  25. 25.
    Baltatu O, Silva JA Jr, Ganten D, Bader M (2000) The brain renin-angiotensin system modulates angiotensin II-induced hypertension and cardiac hypertrophy. Hypertension 35:409–412PubMedGoogle Scholar
  26. 26.
    Masugi Y, Oami H, Aihara K, Hashimoto K, Hakozaki T (1965) Renal and pulmonary vascular changes induced by Crotalaria spectabilis in rats. Acta Pathol Jpn 15:407–415PubMedGoogle Scholar
  27. 27.
    Meyrick B, Gamble W, Reid L (1980) Development of Crotalaria pulmonary hypertension: hemodynamic and structural study. Am J Physiol 239:H692–H702PubMedGoogle Scholar
  28. 28.
    Stenmark KR, Fagan KA, Frid MG (2006) Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ Res 99:675–691CrossRefPubMedGoogle Scholar
  29. 29.
    Johns TN, Olson BJ (1954) Experimental myocardial infarction. I. A method of coronary occlusion in small animals. Ann Surg 140:675–682CrossRefPubMedGoogle Scholar
  30. 30.
    Goldman S, Raya TE (1995) Rat infarct model of myocardial infarction and heart failure. J Card Fail 1:169–177CrossRefPubMedGoogle Scholar
  31. 31.
    Wayman NS, McDonald MC, Chatterjee PK, Thiemermann C (2003) Models of coronary artery occlusion and reperfusion for the discovery of novel antiischemic and antiinflammatory drugs for the heart. Methods Mol Biol 225:199–208PubMedGoogle Scholar
  32. 32.
    Nair KG, Cutilletta AF, Zak R, Koide T, Rabinowitz M (1968) Biochemical correlates of cardiac hypertrophy. I. Experimental model; changes in heart weight, RNA content, and nuclear RNA polymerase activity. Circ Res 23:451–462PubMedGoogle Scholar
  33. 33.
    Barbosa ME, Alenina N, Bader M (2005) Induction and analysis of cardiac hypertrophy in transgenic animal models. Methods Mol Med 112:339–352PubMedGoogle Scholar
  34. 34.
    Flaim SF, Minteer WJ, Nellis SH, Clark DP (1979) Chronic arteriovenous shunt: evaluation of a model for heart failure in rat. Am J Physiol 236:H698–H704PubMedGoogle Scholar
  35. 35.
    Garcia R, Diebold S (1990) Simple, rapid, and effective method of producing aortocaval shunts in the rat. Cardiovasc Res 24:430–432CrossRefPubMedGoogle Scholar
  36. 36.
    Zierhut W, Zimmer HG (1989) Significance of myocardial alpha- and beta-adrenoceptors in catecholamine-induced cardiac hypertrophy. Circ Res 65:1417–1425PubMedGoogle Scholar
  37. 37.
    Stanton HC, Brenner G, Mayfield ED Jr (1969) Studies on isoproterenol-induced cardiomegaly in rats. Am Heart J 77:72–80CrossRefPubMedGoogle Scholar
  38. 38.
    Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91PubMedGoogle Scholar
  39. 39.
    Hiramatsu K, Kassell NF, Goto Y, Soleau S, Lee KS (1993) A reproducible model of reversible, focal, neocortical ischemia in Sprague-Dawley rat. Acta Neurochir (Wien) 120:66–71CrossRefGoogle Scholar
  40. 40.
    Yanamoto H, Nagata I, Niitsu Y, Xue JH, Zhang Z, Kikuchi H (2003) Evaluation of MCAO stroke models in normotensive rats: standardized neocortical infarction by the 3VO technique. Exp Neurol 182:261–274CrossRefPubMedGoogle Scholar
  41. 41.
    Okamoto K, Aoki K (1963) Development of a strain of spontaneously hypertensive rats. Jpn Circ J 27:282–293PubMedGoogle Scholar
  42. 42.
    Louis WJ, Howes LG (1990) Genealogy of the spontaneously hypertensive rat and Wistar-Kyoto rat strains: implications for studies of inherited hypertension. J Cardiovasc Pharmacol 16(Suppl 7):S1–S5PubMedGoogle Scholar
  43. 43.
    Petretto E, Sarwar R, Grieve I, Lu H, Kumaran MK, Muckett PJ, Mangion J, Schroen B, Benson M, Punjabi PP, Prasad SK, Pennell DJ, Kiesewetter C, Tasheva ES, Corpuz LM, Webb MD, Conrad GW, Kurtz TW, Kren V, Fischer J, Hubner N, Pinto YM, Pravenec M, Aitman TJ, Cook SA (2008) Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass. Nat Genet 40:546–552CrossRefPubMedGoogle Scholar
  44. 44.
    Pravenec M, Churchill PC, Churchill MC, Viklicky O, Kazdova L, Aitman TJ, Petretto E, Hubner N, Wallace CA, Zimdahl H, Zidek V, Landa V, Dunbar J, Bidani A, Griffin K, Qi N, Maxova M, Kren V, Mlejnek P, Wang J, Kurtz TW (2008) Identification of renal Cd36 as a determinant of blood pressure and risk for hypertension. Nat Genet 40:952–954CrossRefPubMedGoogle Scholar
  45. 45.
    Bianchi G, Ferrari P, Barber BR (1984) The Milan hypertensive strain. In: de Jong W (ed) Experimental and genetic models of hypertension. Elsevier Science, Oxford, pp 328–349Google Scholar
  46. 46.
    Menini S, Ricci C, Iacobini C, Bianchi G, Pugliese G, Pesce C (2004) Glomerular number and size in Milan hypertensive and normotensive rats: their relationship to susceptibility and resistance to hypertension and renal disease. J Hypertens 22:2185–2192CrossRefPubMedGoogle Scholar
  47. 47.
    Bianchi G, Tripodi G (2003) Genetics of hypertension: the adducin paradigm. Ann N Y Acad Sci 986:660–668CrossRefPubMedGoogle Scholar
  48. 48.
    Vincent M, Dupont J, Sassard J (1979) Simultaneous selection of spontaneously hypertensive, normotensive and lowtensive rats. Jpn Heart J 20(S1):135–137Google Scholar
  49. 49.
    Sassard J, Lo M, Liu KL (2003) Lyon genetically hypertensive rats: an animal model of “low renin hypertension”. Acta Pharmacol Sin 24:1–6PubMedGoogle Scholar
  50. 50.
    Smirk FH, Hall WH (1958) Inherited hypertension in rats. Nature 182:727–728CrossRefPubMedGoogle Scholar
  51. 51.
    Jones DR, Dowd DA (1970) Development of elevated blood pressure in young genetically hypertensive rats. Life Sci 9:247–250CrossRefPubMedGoogle Scholar
  52. 52.
    Ledingham JM, Laverty R (1998) Renal afferent arteriolar structure in the genetically hypertensive (GH) rat and the ability of losartan and enalapril to cause structural remodelling. J Hypertens 16:1945–1952CrossRefPubMedGoogle Scholar
  53. 53.
    Vrana A, Kazdova L (1990) The hereditary hypertriglyceridemic nonobese rat: an experimental model of human hypertriglyceridemia. Transplant Proc 22:2579PubMedGoogle Scholar
  54. 54.
    Heller J, Hellerova S, Dobesova Z, Kunes J, Zicha J (1993) The Prague Hypertensive Rat: a new model of genetic hypertension. Clin Exp Hypertens 15:807–818CrossRefPubMedGoogle Scholar
  55. 55.
    Dahl LK, Heine M, Tassinari L (1962) Role of genetic factors in susceptibility to experimental hypertension due to chronic excess salt ingestion. Nature 194:480–482CrossRefPubMedGoogle Scholar
  56. 56.
    Rapp JP (1982) Dahl salt-susceptible and salt-resistant rats. A review. Hypertension 4:753–763PubMedGoogle Scholar
  57. 57.
    Bashyam H (2007) Lewis Dahl and the genetics of salt-induced hypertension. J Exp Med 204:1507CrossRefPubMedGoogle Scholar
  58. 58.
    Rodriguez-Sargent C, Cangiano JL, Fernandez-Repollet E, Estape-Wainwright E, Torres-Negron I, Martinez-Maldonado M (1988) A new model of genetic hypertension in rats with superficial glomeruli. J Hypertens Suppl 6:S29–S32Google Scholar
  59. 59.
    Ben Ishay D, Saliternik R, Welner A (1972) Separation of two strains of rats with inbred dissimilar sensitivity to Doca-salt hypertension. Experientia 28:1321–1322CrossRefPubMedGoogle Scholar
  60. 60.
    Yagil C, Katni G, Rubattu S, Stolpe C, Kreutz R, Lindpaintner K, Ganten D, Ben Ishay D, Yagil Y (1996) Development, genotype and phenotype of a new colony of the Sabra hypertension prone (SBH/y) and resistant (SBN/y) rat model of salt sensitivity and resistance. J Hypertens 14:1175–1182CrossRefPubMedGoogle Scholar
  61. 61.
    Yagil Y, Yagil C (1998) Genetic basis of salt-susceptibility in the Sabra rat model of hypertension. Kidney Int 53:1493–1500CrossRefPubMedGoogle Scholar
  62. 62.
    Markel AL (1985) Experimental model of inherited arterial hypertension, conditioned by stress. Izvestia Akad Nauk SSSR Seria Biol 3:466–469Google Scholar
  63. 63.
    Maslova LN, Bulygina VV, Markel AL (2002) Chronic stress during prepubertal development: immediate and long-lasting effects on arterial blood pressure and anxiety-related behavior. Psychoneuroendocrinology 27:549–561CrossRefPubMedGoogle Scholar
  64. 64.
    Castle WE, King HD (1947) Linkage studies of the rat. VIII. Fawn, a new colour dilution gene. J Hered 38:341–344PubMedGoogle Scholar
  65. 65.
    Prieur DJ, Meyers KM (1984) Genetics of the fawn-hooded rat strain. The coat color dilution and platelet storage pool deficiency are pleiotropic effects of the autosomal recessive red-eyed dilution gene. J Hered 75:349–352PubMedGoogle Scholar
  66. 66.
    Oiso N, Riddle SR, Serikawa T, Kuramoto T, Spritz RA (2004) The rat Ruby ( R) locus is Rab38: identical mutations in Fawn-hooded and Tester-Moriyama rats derived from an ancestral Long Evans rat sub-strain. Mamm Genome 15:307–314CrossRefPubMedGoogle Scholar
  67. 67.
    Morecroft I, Dempsie Y, Bader M, Walther DJ, Kotnik K, Loughlin L, Nilsen M, MacLean MR (2007) Effect of tryptophan hydroxylase 1 deficiency on the development of hypoxia-induced pulmonary hypertension. Hypertension 49:232–236CrossRefPubMedGoogle Scholar
  68. 68.
    Walther DJ, Peter JU, Winter S, Höltje M, Paulmann N, Grohmann M, Vowinckel J, Alamo-Bethencourt V, Wilhelm CS, Ahnert-Hilger G, Bader M (2003) Serotonylation of small GTPases is a signal transduction pathway that triggers platelet α-granule release. Cell 115:851–862CrossRefPubMedGoogle Scholar
  69. 69.
    Nagaoka T, Gebb SA, Karoor V, Homma N, Morris KG, McMurtry IF, Oka M (2006) Involvement of RhoA/Rho kinase signaling in pulmonary hypertension of the fawn-hooded rat. J Appl Physiol 100:996–1002CrossRefPubMedGoogle Scholar
  70. 70.
    Bonnet S, Michelakis ED, Porter CJ, Andrade-Navarro MA, Thebaud B, Bonnet S, Haromy A, Harry G, Moudgil R, McMurtry MS, Weir EK, Archer SL (2006) An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: similarities to human pulmonary arterial hypertension. Circulation 113:2630–2641CrossRefPubMedGoogle Scholar
  71. 71.
    Brown DM, Provoost AP, Daly MJ, Lander ES, Jacob HJ (1996) Renal disease susceptibility and hypertension are under independent genetic control in the fawn-hooded rat. Nat Genet 12:44–51CrossRefPubMedGoogle Scholar
  72. 72.
    Mccune S, Baker PB, Stills FH (1990) SHHF/Mcc-cp rat: model of obesity, non-insulin dependent diabetes, and congestive heart failure. ILAR News 32:23–27Google Scholar
  73. 73.
    Monti J, Fischer J, Paskas S, Heinig M, Schulz H, Gosele C, Heuser A, Fischer R, Schmidt C, Schirdewan A, Gross V, Hummel O, Maatz H, Patone G, Saar K, Vingron M, Weldon SM, Lindpaintner K, Hammock BD, Rohde K, Dietz R, Cook SA, Schunck WH, Luft FC, Hubner N (2008) Soluble epoxide hydrolase is a susceptibility factor for heart failure in a rat model of human disease. Nat Genet 40:529–537CrossRefPubMedGoogle Scholar
  74. 74.
    Okamoto H, Yamori Y, Nagaoka A (1974) The establishment of the stroke prone hypertensive rat. Circ Res 34(Suppl I):I-143–I-153Google Scholar
  75. 75.
    Yamori Y, Horie R, Tanase H, Fujiwara K, Nara Y, Lovenberg W (1984) Possible role of nutritional factors in the incidence of cerebral lesions in stroke-prone spontaneously hypertensive rats. Hypertension 6:49–53PubMedGoogle Scholar
  76. 76.
    Smeda JS (1989) Hemorrhagic stroke development in spontaneously hypertensive rats fed a North American, Japanese-style diet. Stroke 20:1212–1218PubMedGoogle Scholar
  77. 77.
    McBride MW, Brosnan MJ, Mathers J, McLellan LI, Miller WH, Graham D, Hanlon N, Hamilton CA, Polke JM, Lee WK, Dominiczak AF (2005) Reduction of Gstm1 expression in the stroke-prone spontaneously hypertension rat contributes to increased oxidative stress. Hypertension 45:786–792CrossRefPubMedGoogle Scholar
  78. 78.
    Rentzsch B, Todiras M, Iliescu R, Popova E, Campos LA, Oliveira ML, Baltatu OC, Santos RA, Bader M (2008) Transgenic ACE2 overexpression in vessels of SHRSP rats reduces blood pressure and improves endothelial function. Hypertension 52:967–973CrossRefPubMedGoogle Scholar
  79. 79.
    Böhm M, Lippoldt A, Wienen W, Ganten D, Bader M (1996) Reduction of cardiac hypertrophy in TGR(mREN2)27 by angiotensin II receptor blockade. Mol Cell Biochem 163–164:217–221CrossRefPubMedGoogle Scholar
  80. 80.
    Lee MA, Böhm M, Paul M, Bader M, Ganten U, Ganten D (1996) Physiological characterization of the hypertensive transgenic rat TGR(mREN2)27. Am J Physiol 270:E919–E929PubMedGoogle Scholar
  81. 81.
    Sharma UC, Pokharel S, van Brakel TJ, van Berlo JH, Cleutjens JP, Schroen B, Andre S, Crijns HJ, Gabius HJ, Maessen J, Pinto YM (2004) Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation 110:3121–3128CrossRefPubMedGoogle Scholar
  82. 82.
    Kantachuvesiri S, Fleming S, Peters J, Peters B, Brooker G, Lammie AG, McGrath I, Kotelevtsev Y, Mullins JJ (2001) Controlled hypertension, a transgenic toggle switch reveals differential mechanisms underlying vascular disease. J Biol Chem 276:36727–36733CrossRefPubMedGoogle Scholar
  83. 83.
    Peters B, Grisk O, Becher B, Wanka H, Kuttler B, Ludemann J, Lorenz G, Rettig R, Mullins JJ, Peters J (2008) Dose-dependent titration of prorenin and blood pressure in Cyp1a1ren-2 transgenic rats: absence of prorenin-induced glomerulosclerosis. J Hypertens 26:102–109CrossRefPubMedGoogle Scholar
  84. 84.
    Mitchell KD, Bagatell SJ, Miller CS, Mouton CR, Seth DM, Mullins JJ (2006) Genetic clamping of renin gene expression induces hypertension and elevation of intrarenal Ang II levels of graded severity in Cyp1a1-Ren2 transgenic rats. J Renin Angiotensin Aldosterone Syst 7:74–86CrossRefPubMedGoogle Scholar
  85. 85.
    Howard LL, Patterson ME, Mullins JJ, Mitchell KD (2005) Salt-sensitive hypertension develops after transient induction of ANG II-dependent hypertension in Cyp1a1-Ren2 transgenic rats. Am J Physiol Renal Physiol 288:F810–F815CrossRefPubMedGoogle Scholar
  86. 86.
    Luft FC, Mervaala E, Müller DN, Gross V, Schmidt F, Park JK, Schmitz C, Lippoldt A, Breu V, Dechend R, Dragun D, Schneider W, Ganten D, Haller H (1999) Hypertension-induced end-organ damage: a new transgenic approach to an old problem. Hypertension 33:212–218PubMedGoogle Scholar
  87. 87.
    Pilz B, Shagdarsuren E, Wellner M, Fiebeler A, Dechend R, Gratze P, Meiners S, Feldman DL, Webb RL, Garrelds IM, Jan Danser AH, Luft FC, Muller DN (2005) Aliskiren, a human renin inhibitor, ameliorates cardiac and renal damage in double-transgenic rats. Hypertension 46:569–576CrossRefPubMedGoogle Scholar
  88. 88.
    Bohlender J, Ganten D, Luft FC (2000) Rats transgenic for human renin and human angiotensinogen as a model for gestational hypertension. J Am Soc Nephrol 11:2056–2061PubMedGoogle Scholar

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© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Max-Delbrück-Center for Molecular Medicine (MDC)BerlinGermany

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