The renin-angiotensin system (RAS) controls blood pressure and fluid balance via the binding of angiotensin II (Ang II) to its cell surface receptors. The type 1 receptor (AT1R) triggers signaling cascades that open the arteries to blood flow and increase aldosterone secretion. Blocking this receptor aids in decreasing blood pressure in patients with hypertension due to increased receptor binding.
High Blood Pressure
There are many causes of hypertension and it is often the result of a combination of genetic and environmental factors, including dietary salt, high cholesterol, diabetes, and stress. Genetic abnormalities may consist of increased AT1R activity via higher receptor numbers or binding or increased Ang II.
When AT1R is bound by Ang II, the receptor is internalized by the cell and then recycled to the surface to bind again. When bound by a molecule similar to Ang II, the receptor is not recycled and is unable to be activated by Ang II. This essentially lowers the blood pressure. Drugs that accomplish this are known as angiotensin receptor blockers (ARBs).
ARBs do not work for every patient because they may have other genetic abnormalities contributing to their hypertension. In these cases, other prescriptions are necessary to reduce the blood pressure to physiologically normal levels (less than 140/90 mmHg). Controlling other diseases that contribute to the increased blood pressure is also necessary to ensure treatment success.
Types of ARBs
The sartan family of compounds are angiotensin receptor blockers and are specific for the type 1 receptors. These include irbesartan (Avapro), losartan (Cozaar), candesartan (Atacand), valsartan (Diovan), eprosartan (Tevetan), and telmisartan (Mycardis). Their main difference is in their clearance from the body. Some have been shown to be consistently more efficient in lowering blood pressure, but this is often dependent on the patient and other complications, such as the need for ACE inhibitors, the use of Rifampin, and kidney disease.
ARBs are known to elevate potassium levels and have potential interactions with lithium-based drugs or potassium-salt substitutes, though not many known drug interactions. Side effects are also often mild and due to decreases in blood pressure – dizziness, headache, and drowsiness. An abnormal metallic taste, cough, and rash have also been reported. Serious side effects, including kidney or liver failure, swelling, decreased white blood cells, and allergic reactions are rare, but a doctor should be consulted if irritations or unexpected symptoms occur.
The Contribution of Genetics
The ethnic-based treatment of diseases has been addressed by the Journal of Human Hypertension because of the extent of hypertension in the African-American population. Genetic studies have shown that previously segregated groups have developed increased rates of mutation in RAS genes, among others, which may make them more susceptible to particular pharmaceuticals, such as ARBs. Treatments that address the particular underlying mechanism of increased blood pressure would be more efficient and have fewer side effects than generalized treatments. This includes ARBs, ACE inhibitors, lifestyle changes, and BiDil – the first drug promoted for prescription in a particular ethnic group due to results from clinical trials.
