Journal of Biosciences

, Volume 36, Issue 4, pp 731–737 | Cite as

Animal models for the study of arterial hypertension



Hypertension is one of the leading causes of disability or death due to stroke, heart attack and kidney failure. Because the etiology of essential hypertension is not known and may be multifactorial, the use of experimental animal models has provided valuable information regarding many aspects of the disease, which include etiology, pathophysiology, complications and treatment. The models of hypertension are various, and in this review, we provide a brief overview of the most widely used animal models, their features and their importance.


Blood pressure cardiovascular disease experimental models hypertension 

Abbreviations used:


angiotensin II


borderline hypertensive rat


cerebral blood flow


11-desoxycorticosterone acetate


Dahl salt-resistant rat


Dahl salt-sensitive rat


endothelium-derived constricting factor


endothelium-derived relaxing factor


heart rate


left ventricle


mean arterial pressure


plasma rennin activity


rennin–angiotensin–aldosterone system


reactive oxygen species


renal sympathetic nerve activity


sinoaortic baroreceptors


spontaneously hypertensive rat


stroke-prone spontaneously hypertensive rat


superoxide dismutase




  1. Bachmann S, Peters J, Engler E, Ganten D and Mullins J 1992 Transgenic rats carrying the mouse renin gene: morphological characterization of a low-renin hypertension model. Kidney Int. 41 24–36PubMedCrossRefGoogle Scholar
  2. Bader M, Zhao Y, Sander M, Lee MA, Bachmann J, Böhm M, Djavidani B, Peters J, Mullins JJ and Ganten D 1992 Role of tissue renin in the pathophysiology of hypertension in TGR(mREN2)27 rats. Hypertension 19 681–686PubMedGoogle Scholar
  3. Badyal DK, Lata H and Dadhich A P 2003 Animal models of hypertension and effect of drugs. Indian J. Pharmacol. 35 349–362Google Scholar
  4. Barrett C J, Guild S J, Ramchandra R, Malpas S C 2005 Baroreceptor denervation prevents sympathoinhibition during angiotensin II-induced hypertension; Hypertension 46 168–72PubMedCrossRefGoogle Scholar
  5. Bartunek J, Weinberg EO, Tajima M, Rohrbach S, Katz SE, Douglas PS and Lorell BH 2000 Chronic N G-Nitro-L-Arginine methyl ester-induced hypertension novel molecular adaptation to systolic load in absence of hypertrophy. Circulation 101 423–429PubMedGoogle Scholar
  6. Baylis C, Mitruka B and Deng A 1992 Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glomerular damage. J. Clin. Invest. 90 278–281PubMedCrossRefGoogle Scholar
  7. Bechtold AG, Patel G, Hochhaus G and Scheuer D A 2009 Chronic blockade of hindbrain glucocorticoid receptors reduces blood pressure responses to novel stress and attenuates adaptation to repeated stress. Am. J. Physiol.-Reg. I. 296 R1445–R1454Google Scholar
  8. Biancardi VC, Bergamaschi CT, Lopes OU and Campos RR 2007 Sympathetic activation in rats with L-NAME-induced hypertension. Braz. J. Med. Biol. Res. 40 401–408PubMedCrossRefGoogle Scholar
  9. Campese VM 1994 Salt sensitivity in hypertension: renal and cardiovascular implications. Hypertension 23 531–550PubMedGoogle Scholar
  10. Channa ML, Somova L and Nadar A 2004 Facets of the metabolic syndrome in Dahl hypertensive rats. Cardiovas. J. S. Afr. 15 61–63Google Scholar
  11. Dahl LK, Heine M and Tassinari L 1962 Role of genetic factors in susceptibility to experimental hypertension due to chronic excess salt ingestion. Nature (London) 194 480–482CrossRefGoogle Scholar
  12. DiBona GF and Jones SY 2001 Dynamic analysis of renal nerve activity responses to baroreceptor denervation in hypertensive rats. Hypertension 37 1153–1163PubMedGoogle Scholar
  13. Doggrell SA and Brown L 1998 Rat models of hypertension, cardiac hypertrophy and failure. Cardiovasc. Res. 39 89–105PubMedCrossRefGoogle Scholar
  14. Engelmann GL, Vitullo JC and Gerrity RG 1987 Morphometric analysis of cardiac hypertrophy during development, maturation, and senescence in spontaneously hypertensive rats. Circ. Res. 60 487–494PubMedGoogle Scholar
  15. Esch T, Stefano GB, Fricchione GL and Benson H 2002 Stress in cardiovascular diseases. Med. Sci. Monitor 8 RA93–RA101Google Scholar
  16. Fazan R Jr, da Silva VJD and Salgado HC 2001 Modelos de hipertensão arterial. Braz. J. Hypertens. 8 19–29Google Scholar
  17. Ferrario CM, Varagic J, Habibi J, Nagata S, Kato J, Chappell MC, Trask AJ, Kitamura K, Whaley-Connell A and Sowers JR 2009 Differential regulation of angiotensin-(1-12) in plasma and cardiac tissue in response to bilateral nephrectomy. Am. J. Physiol.-Heart C. 296 H1184–H1192CrossRefGoogle Scholar
  18. Friedman R and Dahl LK 1975 The effect of chronic conflict on the blood pressure of rats with a genetic susceptibility to experimental hypertension. Psychosom. Med. 37 402–416PubMedGoogle Scholar
  19. Fuchs LC, Hoque AM and Clarke NL 1998 Vascular and hemodynamic effects of behavioral stress in borderline hypertensive and Wistar-Kyoto rats. Am. J. Physiol.-Reg. I. 274 R375–R382Google Scholar
  20. Fujiwara N, Osanai T, Kamada T, Katoh T, Takahashi K and Okumura K 2000 Study on the relationship between plasma nitrite and nitrate level and salt sensitivity in human hypertension: modulation of nitric oxide synthesis by salt intake. Circulation 101 856–861PubMedGoogle Scholar
  21. Garwitz ET and Jones AW 1982 Aldosterone infusion into the rat and dose-dependent changes in blood pressure and arterial ionic transport. Hypertension 4 374–381PubMedGoogle Scholar
  22. Gersch M S, Mu W, Cirillo P, Reungjui S, Zhang L, Roncal C, Sautin YY, Johnson RJ and Nakagawa T 2007 Fructose, but not dextrose, accelerates the progression of chronic kidney disease. Am. J. Physiol.-Renal. 293 F1256–F1261CrossRefGoogle Scholar
  23. Giani JF, Mayer MA, Muñoz MC, Silberman E A, Höcht C, Taira CA, Gironacci MM, Turyn D and Dominici FP 2009 Chronic infusion of angiotensin-(1–7) improves insulin resistance and hypertension induced by a high-fructose diet in rats. Am. J. Physiol.-Endoc. M. 296 E262–E271Google Scholar
  24. Goldblatt H, Lynch J, Hanzal RF and Summerville WW 1934 The production of persistent elevation of systolic blood pressure by means of renal ischemia. J. Exp. Med. 59 347–379PubMedCrossRefGoogle Scholar
  25. Guyton AC 1991 Blood pressure control–special role of the kidneys and body fluids. Science 252 1813–1816PubMedCrossRefGoogle Scholar
  26. Hatton D C, Brooks V, Qi Y, McCarron DA 1997 Cardiovascular response to stress: baroreflex resetting and hemodynamics. Am J Physiol; 272 R1588–94PubMedGoogle Scholar
  27. Henning EC, Warach S and Spatz M 2010 Hypertension-induced vascular remodeling contributes to reduced cerebral perfusion and the development of spontaneous stroke in aged SHRSP rats. J. Cerebr. Blood F. Met. 30 827–836CrossRefGoogle Scholar
  28. Henry JP 1975 The induction of acute and chronic cardiovascular disease in animals by psychosocial stimulation. Int. J. Psyc. Med. 6 147–158CrossRefGoogle Scholar
  29. Henry JP, Liu YY, Nadra WE, Qian CG, Mormede P, Lemaire V, Ely D and Hendley ED 1993 Psychosocial stress can induce chronic hypertension in normotensive strains of rats. Hypertension 21 714–723PubMedGoogle Scholar
  30. Itoh H, Mukoyama M, Pratt RE, Gibbons GH and Dzau VJ 1993 Multiple autocrine growth factors modulate vascular smooth muscle cell growth response to angiotensin II. J. Clin. Invest. 91 2268–2274.PubMedCrossRefGoogle Scholar
  31. Kang DG, Moon MK, Sohn EJ, Lee DH and Lee HS 2004 Effects of morin on blood pressure and metabolic changes in fructose-induced hypertensive rats. Biol. Pharm. Bull. 27 1779–1783PubMedCrossRefGoogle Scholar
  32. Krieger EM 1964 Neurogenic hypertension in the rat. Circ. Res. 15 511–521PubMedGoogle Scholar
  33. Ledingham JM and Pelling D 1970 Haemodynamic and other studies in the renoprival hypertensive rat. J. Physiol. 210 233–253PubMedGoogle Scholar
  34. Liard JF, Cowley AW Jr, McCaa RE, McCaa CS and Guyton AC 1974 Renin, aldosterone body fluid volumes and the baroreceptor reflex in the development and reversal of Goldblatt hypertension in conscious dogs. Circ. Res. 34 549–560PubMedGoogle Scholar
  35. McBryde FD, Guild SJ, Barrett CJ, Osborn JW and Malpas SC 2007 Angiotensin II-based hypertension and the sympathetic nervous system: the role of dose and increased dietary salt in rabbits. Exp. Physiol. 92 831–840PubMedCrossRefGoogle Scholar
  36. McCarty R and Gold PE 1996 Catecholamines, stress, and disease: a psychobiological perspective. Psychosom. Med. 58 590–597PubMedGoogle Scholar
  37. Mullins JJ, Peters J and Ganten D 1990 Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene. Nature (London) 344 541–544CrossRefGoogle Scholar
  38. Nagase M, Shibata S, Yoshida S, Nagase T, Gotoda T and Fujita T 2006 Podocyte injury underlies the glomerulopathy of Dahl salt-hypertensive rats and is reversed by aldosterone blocker. Hypertension 47 1084–1093PubMedCrossRefGoogle Scholar
  39. Navarro-Cid J, Maeso R, Perez-Vizcaino F, Cachofeiro V, Ruilope LM, Tamargo J and Lahera V 1995 Effects of losartan on blood pressure, metabolic alterations, and vascular reactivity in the fructose-induced hypertensive rat. Hypertension 26 1074–1078PubMedGoogle Scholar
  40. Okamoto K and Aoki K 1963 Development of a strain of spontaneously hypertensive rats. Jpn. Circulation J. 27 282–293CrossRefGoogle Scholar
  41. Okamoto K, Yamori Y and Nagaoka A 1974 Establishment of stroke-prone spontaneously hypertensive rats (SHR). Circ. Res. 34/35 143–153Google Scholar
  42. Ortiz PA and Garvin JL 2001 Intrarenal transport and vasoactive substances in hypertension. Hypertension 38 621–624PubMedCrossRefGoogle Scholar
  43. Osborn O W, Provo B J 1992 Salt-dependent hypertension in the sinoaortic-denervated rat; Hypertension 19 658–62PubMedGoogle Scholar
  44. Papanek PE, Wood CE and Fregly MJ 1991 Role of the sympathetic nervous system in cold-induced hypertension in rats. J. Appl. Physiol. 71 300–306PubMedGoogle Scholar
  45. Quiroz Y, Ferrebuz A, Romero F, Vaziri ND and Rodriguez-Iturbe B 2008 Melatonin ameliorates oxidative stress, inflammation, proteinuria, and progression of renal damage in rats with renal mass reduction. Am. J. Physiol.-Renal. 294 F336–F344CrossRefGoogle Scholar
  46. Ramchandra R, Barrett C J, Malpas S C 2003 Chronic blockade of nitric oxide does not produce hypertension in baroreceptor denervated rabbits; Hypertension 42 974–77PubMedCrossRefGoogle Scholar
  47. Ribeiro MO, Antunes E, De-Nucci G, Lovisolo SM and Zatz R 1992 Chronic inhibition of nitric oxide synthesis: a new model of arterial hypertension. Hypertension 20 298–303PubMedGoogle Scholar
  48. Ryuzaki M, Suzuki H, Kumagai K, Kumagai H, Ichikawa M, Matsumura Y, Saruta T 1991 Role of vasopressin in salt-induced hypertension in baroreceptor-denervated uninephrectomized rabbits; Hypertension 17 1085–91PubMedGoogle Scholar
  49. Roberts CK, Vaziri ND, Wang XQ and Barnard RJ 2000 Enhanced NO inactivation an hypertension induced by a high-fat, refined-carbohydrate diet. Hypertension 36 423–429PubMedGoogle Scholar
  50. Roberts CK, Vaziri ND, Sindhu RK and Barnard RJ 2003 A high-fat, refined carbohydrate diet affects renal NO synthase protein expression and salt sensitivity. J. Appl. Physiol. 94 941–946PubMedGoogle Scholar
  51. Sanders BJ and Lawler JE 1992 The borderline hypertensive rat (BHR) as a model for environmentally-induced hypertension: a review and update. Neurosci. Biobehav. R. 16 207–217CrossRefGoogle Scholar
  52. Sharma N, Okere IC, Duda MK, Chess DJ, O’Shea KM and Stanley WC 2007 Potential impact of carbohydrate and fat intake on pathological left ventricular hypertrophy. Cardiovasc. Res. 73 257–268PubMedCrossRefGoogle Scholar
  53. Smith TL and Hutchins PM 1979 Central hemodynamics in the developmental stage of spontaneous hypertension in the unanesthetized rat. Hypertension 1 508–517PubMedGoogle Scholar
  54. Steptoe A 1986 Stress mechanisms in hypertension. Postgrad. Med. J. 62 697–699PubMedCrossRefGoogle Scholar
  55. Suzuki H, Saruta T, Ferrario CM and Brosnihan KB 1987 Characterization of neurohormonal changes following the production of the benign and malignant phases of two-kidney, two-clip Goldblatt hypertension. Jpn. Heart J. 28 413–426PubMedCrossRefGoogle Scholar
  56. Thrasher TN 2002 Unloading arterial baroreceptors causes neurogenic hypertension. Am. J. Physiol.-Reg. I. 282 R1044–R1053Google Scholar
  57. Török J 2008 Participation of nitric oxide in different models of experimental hypertension. Physiol. Res. 57 813–825PubMedGoogle Scholar
  58. Trindade Jr AS, Moreira ED, Silva GJJ and Krieger EM 2009 Evidence that blood pressure remains under the control of arterial baroreceptors in renal hypertensive rats. Braz. J. Med. Biol. Res. 42 954–57CrossRefGoogle Scholar
  59. Trippodo NC and Frohlic ED 1981 Similarities of genetic spontaneous hypertension. Circ. Res. 48 309–319PubMedGoogle Scholar
  60. Tucker DC and Hunt RA 1993 Effects of long-term air jet noise and dietary sodium chloride in borderline hypertensive rats. Hypertension 22 527–534PubMedGoogle Scholar
  61. Yamori Y 1989 Predictive and preventive pathology of cardiovascular diseases. Acta Pathol. Japon. 39 683–705Google Scholar
  62. Yamori Y, Horie R, Handa H, Sato M and Fukase M 1976 Pathogenetic similarity of strokes in stroke-prone spontaneously hypertensive rats and humans. Stroke 7 46–53PubMedCrossRefGoogle Scholar
  63. Zeng J, Zhang Y, Mo J, Su Z and Huang R 1998 Two-kidney, two clip renovascular hypertensive rats can be used as stroke-prone rats. Stroke 29 1708–1713PubMedCrossRefGoogle Scholar
  64. Zicha J and Kunes J 1999 Ontogenetic aspects of hypertension development: analysis in the rat. Physiol. Rev. 79 1227–1282PubMedGoogle Scholar
  65. Zimmerman RS and Frohlich ED 1990 Stress and hypertension. J. Hypertens. 8 S103–S107Google Scholar

Copyright information

© Indian Academy of Sciences 2011

Authors and Affiliations

  1. 1.Research in Biological Sciences - NUPEBOuro Preto UniversityMinas GeraisBrazil
  2. 2.Department of Foods, School of NutritionOuro Preto UniversityMinas GeraisBrazil

Personalised recommendations