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ACE inhibitors, ARBs and direct renin inhibitors




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ACE inhibitors, ARBs and direct renin inhibitors


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ACE inhibitors, ARBs and direct renin inhibitors

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Content Reviewers:

Yifan Xiao, MD

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.

Aliskiren has a long half life, so one tablet taken peroral daily is enough.

But, since it’s “younger” in the medical field, it hasn’t been as extensively tested. So it’s commonly used for patients who don’t respond to other antihypertensives, or it can be given in combination with other antihypertensives.

In addition, aliskiren can cause GI side effects like diarrhea and abdominal pain. Other side effects include headache, dizziness, and fatigue.

Okay, so next we have the angiotensin converting enzyme inhibitors, or ACE inhibitors, and their names usually end in “-pril” - like captopril, enalapril, or lisinopril.

So, by inhibiting the action of ACE, they prevent the formation of angiotensin II, and therefore decreases its level in the blood.

With less angiotensin II in the bloodstream, there’s less vasoconstriction and therefore these medications effectively lower the blood pressure.

In addition, they lower aldosterone release, which causes natriuresis, or excretion of sodium by the kidneys.

Captopril should be taken two to three times daily because it has a short half life.

Both enalapril and lisinopril are highly potent, and have a longer half life than captopril.

Because ACE inhibitors are effective in lowering blood pressure, they can be used not only to treat hypertension, but also to treat heart failure, where the heart isn’t strong enough to pump out an adequate amount of blood.

In this situation, the decreased vasoconstriction leads to decreased peripheral vascular resistance and afterload, so the heart doesn’t have to pump as hard against that resistance.

ACE inhibitors should also be given right after someone suffers an acute myocardial infarction in order to increase the perfusion of the heart to prevent further ischemic damage.

Most ACE inhibitors are taken by mouth, and they are eliminated by the kidneys.

So care must be taken with people that suffer from renal impairment, who must receive lower doses.


ACE inhibitors, ARBs and direct renin inhibitors are all medications used to treat high blood pressure. ACE or angiotensin-converting enzyme inhibitors work by blocking the enzyme that converts angiotensin I to angiotensin II. This prevents the body from producing too much of the hormone, which can lead to hypertension. ARBs or angiotensin II receptor blockers work by blocking the receptors that angiotensin II binds to constrict blood vessels. This relaxes the blood vessels and lowers blood pressure. Direct renin inhibitors work by inhibiting renin, the enzyme that converts angiotensinogen to angiotensin I, which also reduces blood pressure. All three of these medications can be used alone or in combination with other medications to safely lower blood pressure.

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