ACE inhibitors, ARBs and direct renin inhibitors

Antihypertensives are a class of medication used to treat hypertension, or high blood pressure.

Certain antihypertensives act upon the renin-angiotensin-aldosterone system to decrease blood pressure by inhibiting vasoconstriction and water reabsorption in the kidneys.

Hypertension affects over a billion people around the world, and it’s a major risk factor for heart disease and stroke.

Blood pressure is the force that blood exerts on the walls of blood vessels.

Now, there’s a number of factors that determine blood pressure. For example, imagine a hose connected to a pump where the hose is the blood vessel and the pump is the heart. If more water is pumped out, the pressure in the hose increases.

Now if we squeeze the hose, narrowing the diameter, the pressure inside would be greater and the water will shoot out more strongly. This is similar to how the diameter of the blood vessels can affect blood pressure, which can change in response to different stimuli.

One important mechanism that regulates blood pressure is the Renin-Angiotensin-Aldosterone System - or RAAS for short - which is a cascade of events that ends up increasing blood pressure.

When blood pressure is low, blood flow to the kidneys decreases. The kidneys respond by secreting renin into the bloodstream.

Renin is a proteolytic enzyme that breaks down a protein made in the liver called angiotensinogen, and this gives rise to angiotensin I.

When it reaches the lungs, angiotensin I is converted into angiotensin II by an enzyme called Angiotensin-converting enzyme, or ACE for short.

Now, angio- refers to the blood vessels; and -tens, well it means “to tense.”

So angiotensin II binds to receptors in vascular smooth muscle and causes them to constrict, which increases the blood pressure.

Finally, angiotensin II also stimulates the release of aldosterone by the adrenal glands.

Aldosterone increases reabsorption of sodium in the kidneys which also increases water reabsorption. This results in increased blood volume, which also increases blood pressure.

Now, there are three main classes of medications that work against - or antagonize - the RAAS.

First, there’s direct renin inhibitors such as aliskiren, which are relatively new compared to other antihypertensives.

Aliskiren binds really tightly to the active site of renin enzymes. This blocks angiotensinogen from binding, so angiotensin I levels fall.