Spontaneously hypertensive rat

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Spontaneously hypertensive rat (SHR) is a laboratory rat which is an animal model of 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]

Contents

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.[ citation needed ]

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.[ citation needed ]

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.[ citation needed ]

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.[ citation needed ]

Other uses

The Spontaneous Hypertensive Rat is also a model for anxiety.[ citation needed ] Extracellular ATP is a mediator of arterial wall hyperplasia and hypertrophy in this model, as notably demonstrated by Jacobson et al 2006 and Kolosova et al 2005 - a regulator of vascular permeability, by the same - and controls smooth muscle cell and blood cell (including monocyte) migration and proliferation, demonstrated in Gerasimovskaya et al 2002, Satterwhite et al 1999, Kaczmarek et al 2005, Lemoli et al 2004, and Rossi et al 2007. [16]

See also

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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". Behavioral Neuroscience of Attention Deficit Hyperactivity Disorder and Its Treatment. pp. 301–15. doi:10.1007/7854_2011_126. hdl:10642/1175. ISBN   978-3-642-24611-1. PMID   21487952.{{cite book}}: |journal= ignored (help)
  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. 1 2 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. S2CID   15649900.
  11. ↑ Dommett EJ (September 2014). "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. S2CID   23214561.
  12. ↑ Turner M, Wilding E, Cassidy E, Dommett EJ (April 2013). "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. S2CID   28836973.
  13. ↑ Brace LR, Kraev I, Rostron CL, Stewart MG, Overton PG, Dommett EJ (September 2015). "Altered visual processing in a rodent model of Attention-Deficit Hyperactivity Disorder" (PDF). Neuroscience. 303: 364–77. doi:10.1016/j.neuroscience.2015.07.003. PMID   26166731. S2CID   38148654.
  14. ↑ Dommett EJ, Rostron CL (November 2011). "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. PMID   21931982. S2CID   18981985.
  15. ↑ Dommett EJ, Rostron CL (February 2013). "Appetitive and consummative responding for liquid sucrose in the spontaneously hypertensive rat model of attention deficit hyperactivity disorder". Behavioural Brain Research. 238: 232–42. doi:10.1016/j.bbr.2012.10.025. PMID   23117093. S2CID   8087378.
  16. ↑ Stenmark KR, Yeager ME, El Kasmi KC, Nozik-Grayck E, Gerasimovskaya EV, Li M, et al. (2013-02-10). "The adventitia: essential regulator of vascular wall structure and function". Annual Review of Physiology. Annual Reviews. 75 (1): 23–47. doi:10.1146/annurev-physiol-030212-183802. PMC   3762248 . PMID   23216413.
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