The renin-angiotensin-aldosterone system explained
When you are diagnosed with high blood pressure, commonly known as hypertension, you are essentially dealing with plumbing that is under too much strain. The force of the blood pushing against the walls of your arteries is consistently too high, which over time can cause serious damage to your heart, brain, and kidneys. To lower this pressure, doctors frequently prescribe medications that target a very specific, powerful hormone cascade in the body known as the renin-angiotensin-aldosterone system, or RAAS.
The RAAS is a complex mechanism your body uses to regulate blood volume and systemic vascular resistance. When your body senses that blood pressure is low, the kidneys release an enzyme called renin. Renin sets off a chain reaction that ultimately produces a potent hormone called angiotensin II. Angiotensin II is a powerful vasoconstrictor—meaning it causes your blood vessels to squeeze and narrow. Imagine pinching a garden hose; the pressure inside the hose immediately increases. Angiotensin II does exactly this to your arteries.
In addition to narrowing the blood vessels, angiotensin II also triggers the release of another hormone called aldosterone, which tells the kidneys to retain sodium and water. This added fluid volume further increases the pressure in the system. While this system is vital for surviving dehydration or blood loss, in patients with chronic hypertension, the RAAS is often inappropriately active, keeping the blood vessels tight and the pressure dangerously high. Both ACE inhibitors and ARBs are designed to disrupt this exact hormonal pathway, forcing the blood vessels to relax and the pressure to fall.
How ACE inhibitors like lisinopril work
ACE inhibitors were the first class of medications developed to target the RAAS pathway. The acronym stands for Angiotensin-Converting Enzyme inhibitors. As the name suggests, these drugs work by blocking a specific enzyme responsible for a crucial step in the hormone cascade. Common medications in this class include lisinopril, ramipril, and enalapril, all of which share the characteristic ‘-pril’ suffix.
To produce the vasoconstricting hormone angiotensin II, the body must first convert a precursor hormone called angiotensin I. This conversion is handled by the Angiotensin-Converting Enzyme (ACE). By taking an ACE inhibitor like lisinopril, you effectively block this enzyme from doing its job. Without the enzyme, the body cannot convert the harmless precursor into the active, pressure-raising hormone. As a result, levels of angiotensin II plummet.
With very little angiotensin II circulating in the blood, the blood vessels are no longer commanded to squeeze tightly. They dilate and relax, creating more space for the blood to flow, which immediately lowers the systemic blood pressure. Furthermore, without the signal from angiotensin II, the body stops retaining excess sodium and water, reducing the overall volume of fluid the heart has to pump. ACE inhibitors are highly effective and are considered a first-line treatment for hypertension, heart failure, and post-heart attack care.
How ARBs like losartan differ from ACE inhibitors
While ACE inhibitors block the production of the problem hormone, ARBs take a different approach. ARB stands for Angiotensin II Receptor Blocker. Medications in this class include losartan, valsartan, and irbesartan, easily identified by their ‘-sartan’ suffix. These drugs act further down the RAAS pathway.
An ARB does not stop the body from producing angiotensin II. The enzyme is still active, and the potent vasoconstricting hormone is still circulating in the bloodstream. However, for a hormone to exert an effect on a cell, it must first bind to a specific receptor on the surface of that cell—like a key fitting into a lock. ARBs are designed to bind precisely to the receptors on the blood vessels where angiotensin II normally attaches.
By occupying these receptors, ARBs physically block angiotensin II from binding. The key is present, but the lock is already jammed. Because the hormone cannot attach to the blood vessels, it cannot transmit the signal to squeeze and narrow. The end clinical result is virtually identical to that of an ACE inhibitor: the blood vessels relax, sodium and water retention decreases, and blood pressure falls significantly. In large-scale clinical trials, ARBs have proven to be just as effective as ACE inhibitors in lowering blood pressure and protecting the cardiovascular system.
The infamous ACE inhibitor dry cough
If ACE inhibitors and ARBs achieve the same end result, why do we need both classes of medication? The answer lies in a very specific, and sometimes frustrating, side effect associated with the ACE enzyme. The Angiotensin-Converting Enzyme does not just convert angiotensin I; it is also responsible for breaking down a different substance in the body called bradykinin.
When you take an ACE inhibitor like lisinopril, you block the enzyme from breaking down bradykinin, leading to higher levels of this substance accumulating in the body, particularly in the respiratory tract. For up to twenty percent of patients, this accumulation of bradykinin triggers a persistent, dry, hacking cough. This cough is not a sign of an infection or lung damage, and it does not respond to over-the-counter cough syrups. It is purely a mechanical side effect of the medication.
For some patients, the cough is mild and tolerable. For others, it is severe enough to disrupt sleep and interfere with daily life. This is where ARBs become invaluable. Because ARBs (like losartan) do not block the ACE enzyme, they do not interfere with the breakdown of bradykinin. Consequently, ARBs do not cause the dry cough. If a patient develops an intolerable cough while taking an ACE inhibitor, the standard medical practice is to discontinue the ACE inhibitor and immediately switch them to an ARB, which usually resolves the cough within a few weeks while maintaining excellent blood pressure control.
Navigating blood pressure goals and combinations
Treating hypertension is rarely a one-and-done scenario. Many patients find that a single medication is not sufficient to bring their blood pressure down to their target range. When this happens, doctors often use a combination of medications that attack high blood pressure from different angles. Because ACE inhibitors and ARBs target the exact same pathway, they are never used together. Taking lisinopril and losartan at the same time does not provide better blood pressure control but dramatically increases the risk of severe kidney damage and dangerously high potassium levels.
Instead, if an ACE inhibitor or an ARB is not enough on its own, it is frequently combined with a medication from a different class. A very common combination is an ACE/ARB paired with a thiazide diuretic (a ‘water pill’ like hydrochlorothiazide) or a calcium channel blocker (like amlodipine). These combinations are highly synergistic; they lower blood pressure far more effectively than merely increasing the dose of a single drug, and they often neutralize each other’s side effects. Many of these combinations are available as a single, combined pill, which greatly simplifies the daily medication routine.
Your specific blood pressure goal will depend on your age and other health conditions. Current guidelines generally recommend aiming for a reading below 130/80 mmHg for most adults. Achieving this goal requires consistency; you must take your medication every day, even when you feel perfectly fine, as high blood pressure is notoriously asymptomatic.
Protecting the kidneys in diabetic patients
Beyond lowering blood pressure, both ACE inhibitors and ARBs possess a unique, highly protective quality: they safeguard the kidneys. This renal protection is particularly vital for patients who have type 1 or type 2 diabetes, a condition that places immense stress on the delicate filtering systems within the kidneys.
Inside the kidney, blood is filtered through tiny clusters of blood vessels called glomeruli. In diabetes, the pressure inside these tiny filters can become abnormally high, forcing proteins (like albumin) to leak out into the urine—an early sign of kidney damage. Both ACE inhibitors and ARBs specifically dilate the blood vessel that exits the glomerulus. By widening the exit pipe, the pressure inside the filter drops significantly. This mechanical relief reduces the stress on the kidney and prevents or slows the leakage of protein.
Because of this powerful protective effect, international medical guidelines strongly recommend that almost all patients with diabetes and high blood pressure, or diabetes and signs of protein in their urine, be prescribed either an ACE inhibitor or an ARB. In this specific clinical scenario, these medications are not just lowering blood pressure; they are actively preserving kidney function and delaying the progression to chronic kidney disease.
Safety considerations during pregnancy and beyond
While ACE inhibitors and ARBs are remarkably safe and effective for the vast majority of adults, they carry a very strict and severe warning regarding pregnancy. Both classes of medication are strictly contraindicated during the second and third trimesters of pregnancy, and guidelines strongly advise against their use during the first trimester or when actively trying to conceive.
If taken during pregnancy, medications that block the RAAS pathway can cause severe, irreversible harm to the developing fetus. The complications can include severe fetal kidney failure, skull malformations, lung underdevelopment, and fetal death. Women of childbearing age who are prescribed an ACE inhibitor or an ARB must use reliable contraception and should have a clear discussion with their doctor about alternative blood pressure medications (such as labetalol or nifedipine) if they are planning to become pregnant.
Aside from pregnancy, both medications require some routine monitoring. Because they change how the kidneys handle electrolytes, they can occasionally cause the body to retain too much potassium—a condition known as hyperkalemia. They can also cause a temporary, usually harmless, bump in serum creatinine, a marker of kidney function. Your doctor will order a simple blood test a few weeks after starting the medication to ensure your kidneys are adapting well and your potassium levels remain safe.
Switching between classes and what to expect
The decision to prescribe an ACE inhibitor or an ARB is often a matter of clinical preference, cost, and patient history. Historically, ACE inhibitors were developed first and were often cheaper, making them the default starting point. Today, generic ARBs are widely available and extremely affordable, leading many prescribers to start directly with an ARB to completely avoid the risk of the dry cough.
If you are currently taking an ACE inhibitor like lisinopril and are experiencing the characteristic dry, hacking cough, or if you develop a rare allergic reaction known as angioedema (swelling of the lips, tongue, or throat), your doctor will likely transition you to an ARB. The switch is generally straightforward and seamless. You will stop the ACE inhibitor one day and start the equivalent dose of the ARB the next day.
There is no ‘better’ medication between the two classes; there is only the medication that your body tolerates best while achieving your target blood pressure. Both classes offer unparalleled cardiovascular protection, kidney preservation, and heart failure management. By understanding how these medications work within your body, you can have a more informed conversation with your healthcare team and take an active role in managing your cardiovascular health.
This article is for informational purposes only and is not a substitute for medical advice from a licensed healthcare professional. Always consult your doctor or pharmacist before starting, changing, or stopping any medication.