Journal of the American Society of Hypertension
Volume 3, Issue 3 , Pages 158-165 , May 2009

Experimental animal models of hypertension

  • Kiran V. Sarikonda, MD

      Affiliations

    • College of Human Medicine, Michigan State University, East Lansing, Michigan, USA
    • ,
  • Ralph E. Watson, MD, FACP

      Affiliations

    • College of Human Medicine, Michigan State University, East Lansing, Michigan, USA
    • Corresponding Author InformationCorresponding author: Ralph E. Watson, MD, FACP, Hypertension Clinic, B338 Clinical Center, College of Human Medicine, Michigan State University, East Lansing, Michigan 48824. Tel: 517-353-4811; fax: 517-432-1326.
    • ,
  • Oluchi C. Opara, MD

      Affiliations

    • College of Human Medicine, Michigan State University, East Lansing, Michigan, USA
    • ,
  • Donald J. DiPette, MD, FAHA

      Affiliations

    • University of South Carolina, School of Medicine, Columbia, South Carolina, USA

Received 7 December 2008 ,Accepted 12 February 2009.

References 

  1. Watson RE, DiPette DJ. Experimental Models of Hypertension. In:  Izzo JL,  Sica DA,  Black HR editor. Hypertension Primer: The Essentials of High Blood Pressure. 4th ed.. Philadelphia, Pennsylvania: Lippincott Williams & Wilkins; 2008;p. 181–183
  2. Lerman LO, Chade AR, Sica V, Napoli C. Animal models of hypertension: an overview. J Lab Clin Med. 2005;146:160–173
  3. Doggrell SA, Brown L. Rat models of hypertension, cardiac hypertrophy, and failure. Cardiovasc Res. 1998;39:89–105
  4. Goldblatt H, Lynch J, Hanzal RF, Summerville WW. Studies on experimental hypertension: I. The production of persistent elevation of systolic blood pressure by means of renal ischemia. J Exp Med. 1934;59:347–379
  5. Gavras H, Brunner HR, Thurston H, Laragh JH. Reciprocation of renin dependency with sodium volume dependency in renal hypertension. Science. 1975;188:1316–1317
  6. Liard J-F, Cowley AW, McCaa RE, McCaa CS, Guyton AC. Renin, aldosterone, body fluid volumes, and the baroreceptor reflex in the development and reversal of Goldblatt hypertension in conscious dogs. Circ Res. 1974;34:549–560
  7. Leenen FH, de Jong W, de Wied D. Renal venous and peripheral plasma renin activity in renal hypertension in the rat. Am J Physiol. 1973;225:1513–1518
  8. Vasilev T, Kiprov D, Puchlev A, Todorova L. Plasma renin activity in patients with renovascular hypertension. Cor Vasa. 1978;20:35–43
  9. Freeman RH, Davis JO, Watkins BE, Stephens GA, DeForrest JM. Effects of continuous converting enzyme blockade on renovascular hypertension in the rat. Am J Physiol Renal Physiol. 1979;236:F21–F24
  10. Brunner HR, Kirshman JD, Sealey JE, Laragh JH. Hypertension of renal origin: evidence for two different mechanisms. Science. 1971;174:1344–1346
  11. Koletsky S, Goodsitt AM. Natural history and pathogenesis of renal ablation hypertension. Arch Pathol. 1960;69:654–662
  12. Ylitalo P, Hepp R, Mohring J, Gross F. Effects of varying sodium intake on blood pressure and renin-angiotensin system in subtotally nephrectomized rats. J Lab Clin Med. 1976;88:807–816
  13. Chi MS, Jones AW, Freeman RH. Increased arterial potassium transport in reduced renal mass hypertension of the rat. Proc Soc Exp Biol Med. 1986;182:229–236
  14. Meyer TW, Anderson S, Rennke HG, Brenner BM. Converting enzyme inhibitor therapy limits progressive glomerular injury in rats with renal insufficiency. Am J Med. 1985;79:31–36
  15. Kanagy NL, Fink GD. Losartan prevents salt-induced hypertension in reduced renal mass rats. J Pharmacol Exp Ther. 1993;265:1131–1136
  16. Kuczera M, Hilgers KF, Lisson C, Ganten D, Hilgenfeldt U, Ritz E, et al. Local angiotensin formation in hindlimbs of uremic hypertensive and renovascular hypertensive rats. J Hypertens. 1991;9:41–48
  17. Moore S, Mersereau WA. Microembolic renal ischemia, hypertension, and nephrosclerosis. Arch Pathol. 1968;85:623–630
  18. Page IH. A method for producing persistent hypertension by cellophane. Science. 1939;89:273–274
  19. Terris JM, Berecek KH, Cohen EL, Stanley JC, Whitehouse WM, Bohr DF. Deoxycorticosterone hypertension in the pig. Clin Sci Mol Med Suppl. 1976;3:303s–5
  20. Zambraski EJ, Ciccone CD, Izzo JL. The role of the sympathetic nervous system in 2-kidney DOCA-hypertensive Yucatan miniature swine. Clin Exp Hypertens A. 1986;8:411–424
  21. Katholi RE, Naftilan AJ, Oparil S. Importance of renal sympathetic tone in the development of DOCA-salt hypertension in the rat. Hypertension. 1980;2:266–273
  22. Mohring J, Mohring B, Petri M, Haack D. Vasopressor role of ADH in the pathogenesis of malignant DOC hypertension. Am J Physiol Renal Physiol. 1977;232:F260–F269
  23. Wilson KM, Sumners C, Hathaway S, Fregly MJ. Mineralocorticoids modulate central angiotensin II receptors in rats. Brain Res. 1986;382:87–96
  24. Matsumura Y, Hashimoto N, Taira S, Kuro T, Kitano R, Ohkita M, et al. Different contributions of endothelin-A and endothelin-B Receptors in the pathogenesis of deoxycorticosterone acetate–salt–induced hypertension in rats. Hypertension. 1999;33:759–765
  25. Li L, Chu Y, Fink GD, Engelhardt JF, Heistad DD, Chen AF. Endothelin-1 stimulates arterial VCAM-1 expression via NADPH oxidase-derived superoxide in mineralocorticoid hypertension. Hypertension. 2003;42:997–1003
  26. Li JS, Schurch W, Schiffrin EL. Renal and vascular effects of chronic endothelin receptor antagonism in malignant hypertensive rats. Am J Hypertens. 1996;9:803–811
  27. Dahl LK, Heine M, Tassinari L. Effects of chronic excess salt ingestion: further demonstration that genetic factors influence the development of hypertension: evidence from experimental hypertension due to cortisone and to adrenal regeneration. J Exp Med. 1965;122:533–545
  28. McCubbin JW, DeMoura RS, Page IH, Olmsted F. Arterial hypertension elicited by subpressor amounts of angiotensin. Science. 1965;149:1394–1395
  29. Ribeiro MO, Antunes E, de Nucci G, Lovisolo SM, Zatz R. Chronic inhibition of nitric oxide synthesis. A new model of arterial hypertension. Hypertension. 1992;20:298–303
  30. Yamada SS, Sassaki AL, Fujihara CK, Avancini Costa Malheiros DM, De Nucci G, Zatz R. Effect of salt intake and inhibitor dose on arterial hypertension and renal injury induced by chronic nitric oxide blockade. Hypertension. 1996;27:1165–1172
  31. Lahera V, Salazar J, Salom MG, Romero JC. Deficient production of nitric oxide induces volume-dependent hypertension. J Hypertens Suppl. 1992;10:S173–S177
  32. Zatz R, Baylis C. Chronic nitric oxide inhibition model six years on. Hypertension. 1998;32:958–964
  33. Smookler HH, Goebel KH, Siegel MI, Clarke DE. Hypertensive effects of prolonged auditory, visual, and motion stimulation. Fed Proc. 1973;32:2105–2110
  34. Coste SC, Qi Y, Brooks VL, McCarron DA, Hatton DC. Captopril and stress-induced hypertension in the borderline hypertensive rat. J Hypertens. 1995;13:1391–1398
  35. Kaufman LN, Peterson MM, Smith SM. Hypertension and sympathetic hyperactivity induced in rats by high-fat or glucose diets. Am J Physiol. 1991;260:E95–E100
  36. Hwang IS, Ho H, Hoffman BB, Reaven GM. Fructose-induced insulin resistance and hypertension in rats. Hypertension. 1987;10:512–516
  37. Fregly MJ. Effects of extremes of temperature on hypertensive rats. Am J Physiol. 1954;176:275–281
  38. Donaldson GC, Robinson D, Allaway SL. An analysis of arterial disease mortality and BUPA health screening data in men, in relation to outdoor temperature. Clin Sci (Lond). 1997;92:261–268
  39. Brennan PJ, Greenberg G, Miall WE, Thompson SG. Seasonal variation in arterial blood pressure. Br Med J (Clin Res Ed). 1982;285:919–923
  40. Papanek PE, Wood CE, Fregly MJ. Role of the sympathetic nervous system in cold-induced hypertension in rats. J Appl Physiol. 1991;71:300–306
  41. Sun Z, Cade R, Zhang Z, Alouidor J. van H. Angiotensinogen gene knockout delays and attenuates cold-induced hypertension. Hypertension. 2003;41:322–327
  42. Sun Z, Cade R, Morales C. Role of central angiotensin II receptors in cold-induced hypertension. Am J Hypertens. 2002;15:85–92
  43. Shechtman O, Fregly MJ, van Bergen P, Papanek PE. Prevention of cold-induced increase in blood pressure of rats by captopril. Hypertension. 1991;17:763–770
  44. Okamoto K, Aoki K. Development of a strain of spontaneously hypertensive rats. Jpn Circ J. 1963;27:282–293
  45. Okamoto K, Yamamoto K, Morita N, Ohta Y, Chikugo T, Higashizawa T, et al. Establishment and use of the M strain of stroke-prone spontaneously hypertensive rat. J Hypertens Suppl. 1986;4:S21–S24
  46. Trippodo NC, Frohlich ED. Similarities of genetic (spontaneous) hypertension. Man and rat. Circ Res. 1981;48:309–319
  47. Mann JF, Phillips MI, Dietz R, Haebara H, Ganten D. Effects of central and peripheral angiotensin blockade in hypertensive rats. Am J Physiol Heart Circ Physiol. 1978;234:H629–H637
  48. DePasquale MJ, Fossa AA, Holt WF, Mangiapane ML. Central DuP 753 does not lower blood pressure in spontaneously hypertensive rats. Hypertension. 1992;19:668–671
  49. Fortepiani LA, Yanes L, Zhang H, Racusen LC, Reckelhoff JF. Role of androgens in mediating renal injury in aging SHR. Hypertension. 2003;42:952–955
  50. Bagby SP, McDonald WJ, Mass RD. Serial renin-angiotensin studies in spontaneously hypertensive and Wistar-Kyoto normotensive rats. Transition from normal- to high-renin status during the established phase of spontaneous hypertension. Hypertension. 1979;1:347–354
  51. Kurtz TW, Morris RC. Biological variability in Wistar-Kyoto rats. Implications for research with the spontaneously hypertensive rat. Hypertension. 1987;10:127–131
  52. St. Lezin E, Simonet L, Pravenec M, Kurtz TW. Hypertensive strains and normotensive 'control' strains. How closely are they related?. Hypertension. 1992;19:419–424
  53. Johnson ML, Ely DL, Turner ME. Genetic divergence between the Wistar-Kyoto rat and the spontaneously hypertensive rat. Hypertension. 1992;19:425–427
  54. Tobian L, Lange JM, Ulm KM, Wold LJ, Iwai J. Potassium prevents death from strokes in hypertensive rats without lowering blood pressure. J Hypertens Suppl. 1984;2:S363–S366
  55. Mashimo T, Nabika T, Matsumoto C, Tamada T, Ueno K, Sawamura M, et al. Aging and salt-loading modulate blood pressure QTLs in rats. Am J Hypertens. 1999;12:1098–1104
  56. Rapp JP, Dene H. Development and characteristics of inbred strains of Dahl salt-sensitive and salt-resistant rats. Hypertension. 1985;7:340–349
  57. Deng Y, Rapp JP. Cosegregation of blood pressure with angiotensin converting enzyme and atrial natriuretic peptide receptor genes using Dahl salt-sensitive rats. Nat Genet. 1992;1:267–272
  58. Smirk FH, Hall WH. Inherited hypertension in rats. Nature. 1958;182:727–728
  59. Ben-Ishay D, Saliternik R, Welner A. Separation of two strains of rats with inbred dissimilar sensitivity to DOCA-salt hypertension. Experientia. 1972;28:1321–1322
  60. Dupont J, Dupont JC, Froment A, Milon H, Vincent M. Selection of three strains of rats with spontaneously different levels of blood pressure. Biomedicine. 1973;19:36–41
  61. Sassard J, Lo M, Liu KL. Lyon genetically hypertensive rats: an animal model of “low-renin hypertension.”. Acta Pharmacol Sin. 2003;24:1–6
  62. Kuijpers MH, Gruys E. Spontaneous hypertension and hypertensive renal disease in the fawn-hooded rat. Br J Exp Pathol. 1984;65:181–190
  63. Dobrian AD, Davies MJ, Prewitt RL, Lauterio TJ. Development of hypertension in a rat model of diet-induced obesity. Hypertension. 2000;35:1009–1015
  64. Alonso-Galicia M, Brands MW, Zappe DH, Hall JE. Hypertension in obese Zucker rats: role of angiotensin II and adrenergic activity. Hypertension. 1996;28:1047–1054
  65. Yamakawa T, Tanaka S-I, Tamura K, Isoda F, Ukawa K, Yamakura Y, et al. Wistar fatty rat is obese and spontaneously hypertensive. Hypertension. 1995;25:146–150
  66. Sutherland DJ, Ruse JL, Laidlaw JC. Hypertension, increased aldosterone secretion and low plasma renin activity relieved by dexamethasone. Can Med Assoc J. 1966;95:1109–1119
  67. Geller DS, Farhi A, Pinkerton N, Fradley M, Moritz M, Spitzer A, et al. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science. 2000;289:119–123
  68. Hanukoglu A. Type I pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects. J Clin Endocrinol Metab. 1991;73:936–944
  69. Shimkets RA, Warnock DG, Bositis CM, Nelson-Williams C, Hansson JH, Schambelan M, et al. Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell. 1994;79:407–414
  70. Simon DB, Nelson-Williams C, Bia MJ, Ellison D, Karet FE, Molina AM, et al. Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Nat Genet. 1996;12:24–30
  71. Mansfield TA, Simon DB, Farfel Z, Bia M, Tucci JR, Lebe M, et al. Multilocus linkage of familial hyperkalaemia and hypertension, pseudohypoaldosteronism type II, to chromosomes 1q31–42 and 17p11-q21. Nat Genet. 1997;16:202–205
  72. Schuster H, Wienker TF, Bahring S, Bilginturan N, Toka HR, Neitzel H, et al. Severe autosomal dominant hypertension and brachydactyly in a unique Turkish kindred maps to human chromosome 12. Nat Genet. 1996;13:98–100
  73. Mullins LJ, Bailey MA, Mullins JJ. Hypertension, kidney, and transgenics: a fresh perspective. Physiol Rev. 2006;86:709–746
  74. Hatada S, Kuziel W, Smithies O, Maeda N. The influence of chromosomal location on the expression of two transgenes in mice. J Biol Chem. 1999;274:948–955
  75. Mullins JJ, Peters J, Ganten D. Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene. Nature. 1990;344:541–544
  76. Montgomery HE, Kiernan LA, Whitworth CE, Fleming S, Unger T, Gohlke P, et al. Inhibition of tissue angiotensin converting enzyme activity prevents malignant hypertension in TGR(mREN2)27. J Hypertens. 1998;16:635–643
  77. Sigmund CD, Jones CA, Kane CM, Wu C, Lang JA, Gross KW. Regulated tissue- and cell-specific expression of the human renin gene in transgenic mice. Circ Res. 1992;70:1070–1079
  78. Yang G, Sigmund CD. Developmental expression of human angiotensinogen in transgenic mice. Am J Physiol. 1998;274:F932–F939
  79. Fukamizu A, Sugimura K, Takimoto E, Sugiyama F, Seo MS, Takahashi S, et al. Chimeric renin-angiotensin system demonstrates sustained increase in blood pressure of transgenic mice carrying both human renin and human angiotensinogen genes. J Biol Chem. 1993;268:11617–11621
  80. Rapp JP, Deng AY. Detection and positional cloning of blood pressure quantitative trait loci: is it possible? Identifying the genes for genetic hypertension. Hypertension. 1995;25:1121–1128
  81. Nadeau JH, Singer JB, Matin A, Lander ES. Analysing complex genetic traits with chromosome substitution strains. Nat Genet. 2000;24:221–225
  82. Lande R, Thompson R. Efficiency of marker-assisted selection in the improvement of quantitative traits. Genetics. 1990;124:743–756
  83. Cowley AW, Liang M, Roman RJ, Greene AS, Jacob HJ. Consomic rat model systems for physiological genomics. Acta Physiol Scand. 2004;181:585–592
  84. Esther CR, Howard TE, Marino EM, Goddard JM, Capecchi MR, Bernstein KE. Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility. Lab Invest. 1996;74:953–965
  85. Sugaya T, Nishimatsu S, Tanimoto K, Takimoto E, Yamagishi T, Imamura K, et al. Angiotensin II type 1a receptor-deficient mice with hypotension and hyperreninemia. J Biol Chem. 1995;270:18719–18722
  86. John SW, Krege JH, Oliver PM, Hagaman JR, Hodgin JB, Pang SC, et al. Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension. Science. 1995;267:679–681
  87. Shesely EG, Maeda N, Kim HS, Desai KM, Krege JH, Laubach VE, et al. Elevated blood pressures in mice lacking endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 1996;93:13176–13181
  88. Williams SM, Haines JL, Moore JH. The use of animal models in the study of complex disease: all else is never equal or why do so many human studies fail to replicate animal findings?. BioEssays. 2004;26:170–179

 This study was supported by the National Institute of Health Grant no. HL73251.

 Conflict of interest: none.

PII: S1933-1711(09)00012-6

doi: 10.1016/j.jash.2009.02.003

Journal of the American Society of Hypertension
Volume 3, Issue 3 , Pages 158-165 , May 2009

Article Tools