RAAS inhibitors are a class of medications primarily used to manage blood pressure and protect major organs, especially the heart and kidneys. These drugs interfere with the body’s natural hormonal system that regulates fluid balance and vascular tone. Because they effectively control hypertension and mitigate disease progression, RAAS inhibitors are widely prescribed in cardiovascular and renal healthcare. Their therapeutic benefits extend beyond simple blood pressure control, making them foundational for managing several chronic conditions.
Understanding the RAAS System
The Renin-Angiotensin-Aldosterone System (RAAS) is a complex hormonal cascade used by the body to maintain blood pressure and fluid volume. When the kidneys detect low blood pressure, they release the enzyme renin, which converts angiotensinogen into angiotensin I. Angiotensin I then encounters Angiotensin-Converting Enzyme (ACE), primarily found on the lining of blood vessels. ACE converts angiotensin I to the highly potent hormone, angiotensin II, the main active component of the system.
Angiotensin II causes vasoconstriction, immediately elevating blood pressure. It also triggers the adrenal glands to release aldosterone, which acts on the kidneys. Aldosterone increases the reabsorption of sodium and water, increasing blood volume and further raising blood pressure. While this response restores blood pressure, chronic overactivation of the system can be damaging.
Categories of RAAS Inhibitors
RAAS inhibitors interrupt the cascade at different points to mitigate the effects of overactivation, offering distinct therapeutic profiles.
Angiotensin-Converting Enzyme (ACE) Inhibitors
This is the most common category, blocking the ACE enzyme from converting angiotensin I to angiotensin II. By preventing the formation of this powerful vasoconstrictor, these medications reduce its concentration in the body. Common examples of this class include lisinopril and enalapril.
Angiotensin II Receptor Blockers (ARBs)
ARBs act further down the cascade by blocking angiotensin II from binding to its main receptors (AT1) on blood vessels and tissues. Even if angiotensin II is produced, ARBs prevent it from exerting its effects. ARBs like losartan and valsartan are often used for patients who cannot tolerate the side effects associated with ACE inhibitors.
Mineralocorticoid Receptor Antagonists (MRAs)
Also known as aldosterone antagonists, MRAs block the effects of aldosterone at its receptor sites, primarily in the kidneys. By preventing aldosterone from promoting sodium and water retention, MRAs like spironolactone and eplerenone increase sodium and water excretion. This action reduces blood volume and lowers blood pressure.
Primary Therapeutic Applications
RAAS inhibitors are foundational for treating hypertension because they directly address two mechanisms that elevate pressure: vasoconstriction and increased blood volume. By relaxing blood vessels and promoting fluid excretion, these medications effectively lower systemic vascular resistance. This sustained pressure reduction helps prevent long-term damage to the cardiovascular system.
For individuals with heart failure, RAAS inhibitors reduce the workload on the heart. The decrease in blood pressure and circulating fluid volume lowers the resistance the heart must pump against, reducing cardiac strain. This action helps prevent or reverse the harmful remodeling of the heart muscle often seen in chronic heart failure, improving overall function.
These medications also play a protective role for the kidneys, especially in patients with diabetes or chronic kidney disease. Angiotensin II typically constricts the efferent arteriole, increasing pressure within the kidney’s filtering units (glomeruli). By lowering this internal pressure, RAAS inhibitors reduce protein loss in the urine (proteinuria) and help slow the progressive decline in kidney function.
Important Safety Considerations
RAAS inhibitors are generally safe and effective, but patients must be aware of important safety considerations and potential side effects.
A common side effect of ACE inhibitors is a persistent, dry cough. This occurs because the ACE enzyme is also involved in breaking down substances like bradykinin, which can accumulate and irritate the airways when the enzyme is blocked. This cough does not typically occur with ARBs, which is why patients are often switched to that class if the cough is bothersome.
A more serious, though rare, side effect across all RAAS inhibitor classes is angioedema. This involves rapid swelling of the deep layers of the skin and can be life-threatening if it affects the throat and obstructs breathing. Patients with a history of angioedema from any RAAS inhibitor must avoid that drug class entirely.
Monitoring of kidney function and electrolyte levels is routine. These medications can sometimes cause a slight increase in serum creatinine or lead to hyperkalemia, an elevated level of potassium in the blood. Hyperkalemia is a particular concern because RAAS inhibition reduces aldosterone’s ability to promote potassium excretion. Patients require regular blood tests to check potassium levels, especially if they are also taking potassium-sparing diuretics or potassium supplements.
RAAS inhibitors are strictly contraindicated during pregnancy because they pose a significant risk of severe developmental problems and death to the fetus, particularly during the second and third trimesters. Combining an ACE inhibitor and an ARB is generally not recommended due to an increased risk of adverse events like hyperkalemia and acute kidney injury.