Spontaneously hypertensive rat

Spontaneously hypertensive rat (SHR) is a laboratory rat which is an animal model of essential (or primary) hypertension, used to study cardiovascular disease. It is the most studied model of hypertension measured as number of publications.[1] The SHR strain was obtained during the 1960s by Okamoto and colleagues, who started breeding Wistar-Kyoto rats with high blood pressure.[2]

Pathophysiology

Hypertensive development begins around 5–6 weeks of age, reaching systolic pressures between 180 and 200 mmHg in the adult age phase. Starting between 40 and 50 weeks, SHR develops characteristics of cardiovascular disease, such as vascular and cardiac hypertrophy.[3]

Blood pressure in SHR depends on the kidney

Hypertensive development is somehow connected to the kidney. Transplanting a kidney from SHR to a normotensive Wistar rat increases blood pressure in the recipient. Conversely, transferring a Wistar kidney to SHR normalizes blood pressure in the recipient.[4] This also happens if transplantation takes place at young age before established hypertension in the donors,[5] indicating a primary role for the kidney in the development of hypertension in SHR.

SHR and coping

Even though SHR is usually considered to be a purely pathological model, the strain exhibit interesting compensatory abilities. For example, kidneys transplanted from SHR to a hypertensive recipient retain better morphology than kidneys transplanted from Brown Norway,[6] demonstrating a pathological adaptation to high blood pressure.[7]

The stroke prone SHR

Stroke prone SHR (SHR-SP) is a further development of SHR that has even higher blood pressure than SHR and a strong tendency to die from stroke.

Attention Deficit Hyperactivity Disorder

The Spontaneously Hypertensive Rat (SHR) is also used as a model of attention-deficit hyperactivity disorder. Research by Terje Sagvolden suggested that rats sourced from Charles River Laboratories perform as the best model.[8][9][10] If the animal is to be used as a model of ADHD, it is generally advised to start testing when the animals are around four weeks old (28 postnatal days) before the onset of hypertension.

Despite the criticisms associated with using animals to research essentially human conditions, Sagvolden supported his Dynamic Developmental Theory of ADHD using research primarily done using Spontaneously Hypertensive Rats.[10] In addition, numerous studies have been conducted in the SHR in relation to other elements of ADHD, for example, looking at the impact of different drug treatments such as atomoxetine and methylphenidate on tests of impulsivity and attention[11] and hyperactivity,[12] investigating possible neural correlates of heightened distractibility in ADHD[13][14] and assessing reward function.[15]

Reference strain

The reference strain to best illustrate the ADHD-like deficits of the SHR is the Sprague-Dawley. Although some argue that the deficits are only present because the Sprague-Dawley is naturally less active anyway.

Other uses

The Spontaneous Hypertensive Rat is also a model for anxiety.

See also
  • Animal models of ischemic stroke

References
  1. Pinto YM, Paul M, Ganten D (July 1998). "Lessons from rat models of hypertension: from Goldblatt to genetic engineering". Cardiovascular Research. 39 (1): 77–88. doi:10.1016/S0008-6363(98)00077-7. PMID 9764191.
  2. Okamoto K, Aoki K (March 1963). "Development of a strain of spontaneously hypertensive rats". Japanese Circulation Journal. 27 (3): 282–93. doi:10.1253/jcj.27.282. PMID 13939773.
  3. Conrad CH, Brooks WW, Hayes JA, Sen S, Robinson KG, Bing OH (January 1995). "Myocardial fibrosis and stiffness with hypertrophy and heart failure in the spontaneously hypertensive rat". Circulation. 91 (1): 161–70. doi:10.1161/01.cir.91.1.161. PMID 7805198.
  4. Kawabe K, Watanabe TX, Shiono K, Sokabe H (November 1978). "Influence on blood pressure of renal isografts between spontaneously hypertensive and normotensive rats, utilizing the F1 hybrids". Japanese Heart Journal. 19 (6): 886–94. doi:10.1536/ihj.19.886. PMID 374777.
  5. Rettig R (April 1993). "Does the kidney play a role in the aetiology of primary hypertension? Evidence from renal transplantation studies in rats and humans". Journal of Human Hypertension. 7 (2): 177–80. PMID 8510091.
  6. Churchill PC, Churchill MC, Griffin KA, et al. (May 2002). "Increased genetic susceptibility to renal damage in the stroke-prone spontaneously hypertensive rat". Kidney International. 61 (5): 1794–800. doi:10.1046/j.1523-1755.2002.00321.x. PMID 11967029.
  7. http://www.emrgnc.com.au/apithology.htm%5B%5D
  8. Sagvolden T, Johansen EB (2012). Rat models of ADHD. Current Topics in Behavioral Neurosciences. 9. pp. 301–15. doi:10.1007/7854_2011_126. hdl:10642/1175. ISBN 978-3-642-24611-1. PMID 21487952.
  9. Sagvolden T, Johansen EB, Wøien G, et al. (December 2009). "The spontaneously hypertensive rat model of ADHD--the importance of selecting the appropriate reference strain". Neuropharmacology. 57 (7–8): 619–26. doi:10.1016/j.neuropharm.2009.08.004. PMC 2783904. PMID 19698722.
  10. Sagvolden T, Johansen EB, Aase H, Russell VA (June 2005). "A dynamic developmental theory of attention-deficit/hyperactivity disorder (ADHD) predominantly hyperactive/impulsive and combined subtypes". The Behavioral and Brain Sciences. 28 (3): 397–419, discussion 419–68. doi:10.1017/S0140525X05000075. PMID 16209748.
  11. Dommett, Eleanor J. (2014-09-01). "Using the five-choice serial reaction time task to examine the effects of atomoxetine and methylphenidate in the male spontaneously hypertensive rat". Pharmacology Biochemistry and Behavior. 124: 196–203. doi:10.1016/j.pbb.2014.06.001. PMID 24933335.
  12. Turner, Michael; Wilding, Emma; Cassidy, Emmet; Dommett, Eleanor J. (2013-04-15). "Effects of atomoxetine on locomotor activity and impulsivity in the spontaneously hypertensive rat". Behavioural Brain Research. 243: 28–37. doi:10.1016/j.bbr.2012.12.025. PMID 23266523.
  13. Brace, L.R.; Kraev, I.; Rostron, C.L.; Stewart, M.G; Overton, P.G.; Dommett, E.J. (2015). "Altered visual processing in a rodent model of Attention-Deficit Hyperactivity Disorder" (PDF). Neuroscience. 303: 364–377. doi:10.1016/j.neuroscience.2015.07.003. PMID 26166731.
  14. Dommett, Eleanor J.; Rostron, Claire L. (2011-11-01). "Abnormal air righting behaviour in the spontaneously hypertensive rat model of ADHD". Experimental Brain Research. 215 (1): 45–52. doi:10.1007/s00221-011-2869-7. ISSN 0014-4819. PMID 21931982.
  15. Dommett, Eleanor J.; Rostron, Claire L. (2013-02-01). "Appetitive and consummative responding for liquid sucrose in the spontaneously hypertensive rat model of attention deficit hyperactivity disorder". Behavioural Brain Research. 238: 232–242. doi:10.1016/j.bbr.2012.10.025. PMID 23117093.
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