Drugs Affecting the Renin-Angiotensin-Aldosterone System

Core Concepts

The cascade, step by step

The RAAS starts in the kidney. When renal blood flow or pressure falls (as in heart failure), the juxtaglomerular cells release renin, which converts angiotensinogen (from the liver) into inactive angiotensin I. Angiotensin-converting enzyme (ACE), found mainly in the lungs, then converts angiotensin I into angiotensin II, the system's powerful active hormone.

Angiotensin II matters here for three effects: it constricts blood vessels (via AT1 receptors, raising afterload); it stimulates aldosterone release, which makes the kidney's collecting duct retain sodium and water (raising preload) while wasting potassium; and it promotes remodeling — growth and fibrosis of heart muscle.

In heart failure, low cardiac output keeps the RAAS switched on. Vasoconstriction and fluid retention support blood pressure short-term but chronically raise a failing heart's workload and drive structural damage. The logic of therapy: interrupt the cascade, lower the workload, slow the remodeling.

ACE inhibitors: stop the enzyme

ACE inhibitors (generic names typically end in -pril) block the conversion of angiotensin I to angiotensin II. Less angiotensin II means less vasoconstriction, less aldosterone release, and less remodeling — in effect, lower afterload and preload without directly stimulating the heart.

A key detail: ACE also degrades bradykinin, a vasodilating peptide. When ACE is blocked, bradykinin accumulates — contributing to the benefit but also to two signature adverse effects:

• Dry cough — common, bothersome, not life-threatening; a frequent reason for switching classes.
• Angioedema — swelling of the face, lips, tongue, or airway; rare but potentially life-threatening and an emergency. A person who develops angioedema should not simply be rechallenged; the prescriber decides next steps (often an ARB, though angioedema can rarely occur there too).

Because angiotensin II supports glomerular filtration, ACE inhibitors can lower kidney function and raise potassium — baseline and periodic monitoring is expected.

ARBs: block the receptor instead

ARBs (generic names typically end in -sartan) do not stop angiotensin II production; they block its main receptor (AT1), so the angiotensin II present cannot act. Clinical benefits overlap heavily with ACE inhibitors, but because ARBs do not raise bradykinin, dry cough is much less common. Angioedema is still possible but rare.

ACE inhibitors and ARBs should not be used together routinely: they block the same pathway at adjacent steps, adding risk (hypotension, kidney injury, hyperkalemia) without proven added benefit. Guidance treats them as alternatives, not partners.

ARNI: add the brake on peptide breakdown

ARNI (angiotensin receptor–neprilysin inhibitor) combines an ARB (valsartan) with a neprilysin inhibitor (sacubitril). Neprilysin breaks down the protective natriuretic peptides (ANP, BNP); inhibiting it lets them last longer, producing vasodilation and sodium loss that complement AT1 blockade.

Because both ARNI and ACE inhibitors raise bradykinin-related angioedema risk, ARNI is not used together with an ACE inhibitor (a washout period is standard when switching — verify current guidance). ARNI is used in HFrEF per current guidelines with the same potassium and renal monitoring as other RAAS blockers.

MRAs (aldosterone antagonists): block the last step

Mineralocorticoid receptor antagonists — spironolactone and eplerenone — block aldosterone at its receptor in the collecting duct. Sodium and water excretion increase, potassium is retained, and aldosterone's direct remodeling/fibrosis effects on heart and vessels are reduced. In HFrEF, MRAs reduce mortality and hospitalizations and are part of the standard regimen.

Two cautions follow from the mechanism:

• Hyperkalemia is the main risk, especially with a concurrent ACE inhibitor or ARB (both also raise potassium) or impaired kidney function — so potassium and renal monitoring is expected.
• Spironolactone also binds progesterone and androgen receptors, causing gynecomastia and menstrual changes; eplerenone is more selective and causes these less often.

MRAs are sometimes loosely grouped with "potassium-sparing diuretics," but they are distinct: their heart-failure benefit goes beyond urine output because aldosterone blockade directly reduces remodeling.

Nursing implications across the class

At the bedside, RAAS drugs share a monitoring pattern: blood pressure, renal function, and potassium. Teach the person to report dizziness, muscle weakness or palpitations (possible electrolyte disturbance), facial or lip swelling (possible angioedema — urgent), and a new persistent cough (with ACE inhibitors). Adherence matters because the benefit is long-term, not a symptom fix. Scope varies by state and institution — local policy and prescriber orders define what the nurse may initiate, adjust, or monitor.

Common Confusions