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Spontaneously hypertensive rat (SHR) is a laboratory rat which is an animal model of essential (or primary)
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
, used to study
cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
. It is the most studied model of hypertension measured as number of publications. The SHR strain was obtained during the 1960s by Okamoto and colleagues, who started breeding Wistar-Kyoto rats with high
blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...
.


Pathophysiology

Hypertensive development begins around 5–6 weeks of age, reaching
systolic Systole ( ) is the part of the cardiac cycle during which some chambers of the heart contract after refilling with blood. The term originates, via New Latin, from Ancient Greek (''sustolē''), from (''sustéllein'' 'to contract'; from ''sun ...
pressures between 180 and 200
mmHg A millimetre of mercury is a manometric unit of pressure, formerly defined as the extra pressure generated by a column of mercury one millimetre high, and currently defined as exactly pascals. It is denoted mmHg or mm Hg. Although not an SI ...
in the adult age phase. Starting between 40 and 50 weeks, SHR develops characteristics of cardiovascular disease, such as vascular and cardiac hypertrophy.


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. This also happens if transplantation takes place at young age before established hypertension in the donors, 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, demonstrating a pathological adaptation to high blood pressure.


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 Charles River Laboratories International, Inc., is an American pharmaceutical company specializing in a variety of preclinical and clinical laboratory, gene therapy and cell therapy services for the Pharmaceutical, Medical device and Biotechnolo ...
perform as the best model. 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. 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 and hyperactivity, investigating possible neural correlates of heightened distractibility in ADHD and assessing reward function.


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
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is a mediator of
arterial wall An artery (plural arteries) () is a blood vessel in humans and most animals that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are the pul ...
hyperplasia Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferati ...
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
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, demonstrated in Gerasimovskaya et al 2002, Satterwhite et al 1999, Kaczmarek et al 2005, Lemoli et al 2004, and Rossi et al 2007.


See also

* Animal models of ischemic stroke


References

{{Reflist Laboratory rat strains