Spontaneously hypertensive rat explained

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]

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. 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

References

Notes and References

  1. Pinto YM, Paul M, Ganten D . Lessons from rat models of hypertension: from Goldblatt to genetic engineering . Cardiovascular Research . 39 . 1 . 77–88 . July 1998 . 9764191 . 10.1016/S0008-6363(98)00077-7. free .
  2. Okamoto K, Aoki K . Development of a strain of spontaneously hypertensive rats . Japanese Circulation Journal . 27 . 3. 282–93 . March 1963 . 13939773 . 10.1253/jcj.27.282. free .
  3. Conrad CH, Brooks WW, Hayes JA, Sen S, Robinson KG, Bing OH . Myocardial fibrosis and stiffness with hypertrophy and heart failure in the spontaneously hypertensive rat . Circulation . 91 . 1 . 161–70 . January 1995 . 7805198 . 10.1161/01.cir.91.1.161.
  4. Kawabe K, Watanabe TX, Shiono K, Sokabe H . Influence on blood pressure of renal isografts between spontaneously hypertensive and normotensive rats, utilizing the F1 hybrids . Japanese Heart Journal . 19 . 6 . 886–94 . November 1978 . 374777. 10.1536/ihj.19.886 . free .
  5. Rettig R . 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 . April 1993 . 8510091.
  6. Churchill PC, Churchill MC, Griffin KA, etal . Increased genetic susceptibility to renal damage in the stroke-prone spontaneously hypertensive rat . Kidney International . 61 . 5 . 1794–800 . May 2002 . 11967029 . 10.1046/j.1523-1755.2002.00321.x. free .
  7. http://www.emrgnc.com.au/apithology.htm{{full citation needed|date=December 2014}}
  8. Book: Sagvolden T, Johansen EB . Behavioral Neuroscience of Attention Deficit Hyperactivity Disorder and Its Treatment . Rat models of ADHD . Current Topics in Behavioral Neurosciences . 9 . 301–15 . 2012 . 21487952 . 10.1007/7854_2011_126. 978-3-642-24611-1 . 10642/1175 .
  9. Sagvolden T, Johansen EB, Wøien G, etal . The spontaneously hypertensive rat model of ADHD--the importance of selecting the appropriate reference strain . Neuropharmacology . 57 . 7–8 . 619–26 . December 2009 . 19698722 . 2783904 . 10.1016/j.neuropharm.2009.08.004.
  10. Sagvolden T, Johansen EB, Aase H, Russell VA . 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 . June 2005 . 16209748 . 10.1017/S0140525X05000075. 15649900 .
  11. Dommett EJ . 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 . September 2014 . 24933335 . 10.1016/j.pbb.2014.06.001 . 23214561 .
  12. Turner M, Wilding E, Cassidy E, Dommett EJ . Effects of atomoxetine on locomotor activity and impulsivity in the spontaneously hypertensive rat . Behavioural Brain Research . 243 . 28–37 . April 2013 . 23266523 . 10.1016/j.bbr.2012.12.025 . 28836973 .
  13. Brace LR, Kraev I, Rostron CL, Stewart MG, Overton PG, Dommett EJ . Altered visual processing in a rodent model of Attention-Deficit Hyperactivity Disorder . Neuroscience . 303 . 364–77 . September 2015 . 26166731 . 10.1016/j.neuroscience.2015.07.003 . 38148654 .
  14. Dommett EJ, Rostron CL . Abnormal air righting behaviour in the spontaneously hypertensive rat model of ADHD . Experimental Brain Research . 215 . 1 . 45–52 . November 2011 . 21931982 . 10.1007/s00221-011-2869-7 . 18981985 .
  15. Dommett EJ, Rostron CL . Appetitive and consummative responding for liquid sucrose in the spontaneously hypertensive rat model of attention deficit hyperactivity disorder . Behavioural Brain Research . 238 . 232–42 . February 2013 . 23117093 . 10.1016/j.bbr.2012.10.025 . 8087378 .
  16. Stenmark KR, Yeager ME, El Kasmi KC, Nozik-Grayck E, Gerasimovskaya EV, Li M, Riddle SR, Frid MG . 6 . The adventitia: essential regulator of vascular wall structure and function . Annual Review of Physiology . 75 . 1 . 23–47 . 2013-02-10 . 23216413 . 10.1146/annurev-physiol-030212-183802. 3762248 . .

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