The renin–angiotensin–aldosterone system !

Regulation
Exam priority: high

When blood pressure or salt falls, the kidney releases renin, starting a chain of hormones that tightens vessels and holds salt and water.

Updated 2026-11-01

Also called: RAAS, Angiotensin II

See it in 3D: Kidneys · Left adrenal gland · Right adrenal gland · Liver · Left renal artery

What it is

The RAAS is a hormone cascade that defends blood volume and pressure. Renin from the kidney converts liver angiotensinogen into angiotensin I, which ACE (mostly in the lung endothelium) converts to angiotensin II. Angiotensin II constricts arterioles, makes the kidney keep Na⁺, and stimulates aldosterone, thirst and ADH.

How it works, step by step

Low renal perfusion, low NaCl delivery to the macula densa or β1 sympathetic stimulation trigger renin release from juxtaglomerular cells.
Renin cleaves angiotensinogen (from the liver) to angiotensin I.
ACE on endothelial cells, especially in the lung, converts angiotensin I to angiotensin II.
Angiotensin II constricts arterioles (raises SVR) and the efferent arteriole (keeps GFR).
It increases Na⁺ reabsorption in the proximal tubule and stimulates aldosterone from the adrenal zona glomerulosa.
Aldosterone adds Na⁺ channels and pumps in the collecting duct: Na⁺ and water retained, K⁺ secreted.
Angiotensin II also stimulates thirst and ADH; volume and pressure rise and renin release falls (negative feedback).

Hormone axes and feedback

Renin–angiotensin–aldosterone systemLesion None (normal)

Tap a box to see the hormone, or choose a lesion to see the lab pattern.

Stimulates (+)
Inhibits / negative feedback (−)
Level ↑
Level ↓

Tap each organ in the cascade to see what it adds and what feeds back.

The nephron: segments, transporters and diuretics

Juxtaglomerular apparatus (macula densa) NaCl sensor · releases renin

Juxtaglomerular apparatus (macula densa)

What it does: The macula densa, at the end of the thick limb, senses the NaCl arriving: more NaCl constricts the afferent arteriole (tubuloglomerular feedback, adenosine) and curbs renin; less NaCl stimulates renin. Granular (juxtaglomerular) cells of the afferent arteriole secrete renin.
Transporters: NKCC2 in the macula densa (the NaCl sensor).
Hormones: Renin release: lower afferent pressure, less NaCl at the macula densa and sympathetic (β1) input. Renin → Ang I → Ang II (ACE) → aldosterone.
Drugs: Beta blockers lower renin; loop diuretics blind the sensor (more renin); ACE inhibitors, ARBs and direct renin inhibitors block the axis.
Disorders: Renal artery stenosis (renovascular hypertension with high renin); juxtaglomerular cell tumor (rare).

Glomerulus and arterioles
Proximal tubule
Thin descending limb
Thin ascending limb
Thick ascending limb
Distal convoluted tubule
Collecting tubule and duct
Juxtaglomerular apparatus (macula densa)
Cortex
Medulla
Interstitial osmolality (≈ 300 → 1200 mOsm/kg)

Illustrative schematic drawn by Durgical (a long-loop juxtamedullary nephron); proportions and percentages are approximate and not for clinical decisions.

Regulation

+Low renal perfusion pressure: More renin from the afferent arteriole (intrarenal baroreceptor).
+Renal sympathetic nerves (β1): More renin.
+High plasma K⁺: Directly stimulates aldosterone secretion.
−Atrial natriuretic peptide: Inhibits renin and aldosterone; promotes Na⁺ loss.
−High NaCl at the macula densa, angiotensin II itself: Less renin (feedback).

Where drugs act on the cascade

Step	Drug class	Key consequence
Renin release (β1)	Beta blockers	Less renin
Angiotensin I → II	ACE inhibitors	Less Ang II, more bradykinin (cough)
AT1 receptor	Angiotensin II receptor blockers	Block Ang II effects, no bradykinin rise
Aldosterone receptor	Mineralocorticoid receptor antagonists	Less Na⁺ retention, K⁺ can rise

Clinical notes

Primary hyperaldosteronism: hypertension with low K⁺ and low renin.
Renal artery stenosis: high renin hypertension; with bilateral stenosis, ACE inhibitors can cause acute kidney injury.

Test yourself

Think of the answer, then tap the question to see it.

What are the three main stimuli for renin release?

Low perfusion pressure in the afferent arteriole, low NaCl delivery sensed by the macula densa, and renal sympathetic stimulation through β1 receptors.

How does angiotensin II help preserve GFR when renal blood flow falls?

It constricts the efferent arteriole more than the afferent, raising glomerular capillary pressure and the filtration fraction.

Why do ACE inhibitors cause a dry cough while ARBs rarely do?

ACE also degrades bradykinin; blocking it raises bradykinin in the airways. ARBs block the AT1 receptor and do not affect bradykinin breakdown.

Why can blocking aldosterone or angiotensin II raise plasma K⁺?

Aldosterone drives K⁺ secretion in the collecting duct by adding Na⁺ channels and Na⁺/K⁺ pumps; less aldosterone action means less K⁺ excreted.

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See it in 3D

The structures of Durgical's 3D anatomy where it happens.

In Biochemistry

In Pharmacology

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Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: 20.4 Homeostatic Regulation of the Vascular System (OpenStax (Rice University), 2022); 26.3 Electrolyte Balance (OpenStax (Rice University), 2022); Essential Hypertension (StatPearls (NCBI Bookshelf), 2025); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 19). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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Representative model, for educational purposes only.