Background

Hypertension or high blood pressure affects approximately 25% of the adult population in the United States. Blood pressure is defined by measuring both systolic and diastolic pressures in pounds per square inch (psi). Normal blood pressure in humans is defined as Less than 120/80. Hypertension is measured in 3 phases: Prehypertension: 120/80-139/89, Stage 1 hypertension: 140/90 -159/99 and Stage 2 hypertension: 160 and above/100 and above. The exact causes of hypertension are not known. Several factors and conditions may play a role in its development, including: Smoking, being overweight, lack of physical activity, too much salt in the diet, excess alcohol consumption, stress, older age, genetics/family history, chronic kidney disease and adrenal and thyroid disorders. Hypertension is frequently assympomatic, but severe hypertension may cause the following symptoms: severe headache, fatigue or confusion, vision problems, chest pain, difficulty breathing, irregular heartbeat and blood in the urine Untreated, hypertension that can damage the heart and blood vessels, and can eventually lead to several other conditions, including: Stroke, heart failure, heart attack, kidney failure and vision problems. The exact mortality and morbidity, and therefore societal cost associated with hypertension is difficult to estimate because of the wide variety of conditions that are associated with hypertension, either as a cause of the hypertension or a consequence.

Treatment for hypertension is usually treated with a two strategy approach. The first strategy to treating hypertension is by making lifestyle changes, such as losing weight, stopping smoking, eating a healthy diet, and getting enough exercise, especially aerobic exercise. The second strategy is to use drugs to treat hypertension. The drugs available to treat hypertension fall into a number of categories including ACE inhibitors, angiotensin receptor blockers (ARBs), diuretics, beta-blockers, and calcium channel blockers.

Animal models of Hypertension

Animal models of hypertension fall into several categories. There are several animal models of spontaneous hypertension, which are often referred to as genetic models and are relevant to essential hypertension in humans. The surgical models of hypertension in which the blood supply to the kidneys is restricted, or the kidneys are surgically reduced are relevant to renal artery stenosis and kidney disease in humans. Diet related models of obesity and increase salt intake are directly relevant to the equivalent conditions in humans.

The Spontaneous Hypertensive Rat (SHR) model of Hypertension

The SHR inbred rat strain was derived by mating Wistar Kyoto (WKY) rats with spontaneous hypertension and then maintaining an inbred strain via repeated brother – sister matings. Both males and females are hypertensive from about 10 weeks of age (Tanase et al 1982), systolic blood pressure plateaus at about 200 mmHg at about 15 weeks. SHR rats have a high incidence of cardiovascular disease (Okamoto et al 1973), but a low incidence of stroke which can be increased to about 30% with chronic stress (Yamori 1984). Grobecker et al (1975) found that in young SHR rats the plasma levels of both noradrenaline and dopamine-ß-hydroxylase were increased over control WKY rats, but total catecholamines were not significantly different. Catecholamine content of the adrenals was reduced. Circulating thyrotrophin levels were markedly elevated over two control strains (Werner et al 1975). Caloric restriction lowers blood pressure (Young et al 1978). Environmental and dietary factors can influence the degree of hypertension (Yamori et al 1979, 1986). A high (8%) salt diet increased systolic blood pressure (Adams and Blizard, 1991).