Candesartan: the pathway in the body
Candesartan is part of the pathway “Candesartan”. This page shows the whole pathway; the station of Candesartan is highlighted.
Where this laboratory value sits: Candesartan — active form with tetrazole. Candesartan is the form that acts at the receptor. It carries an acid group and a tetrazole ring; both reach into the binding pocket of the AT1 receptor and come away from it only slowly. Even a lot of angiotensin II hardly displaces it. Source 3, 6
In brief
Candesartan is an AT1 receptor antagonist, given as an ester precursor. It occupies the pocket of the receptor into which angiotensin II otherwise reaches, and comes away only slowly — the messenger still arises but finds the pocket taken. The vessels thus stay wider.
What this is about
Angiotensin II is the most potent vessel-narrowing messenger of the renin-angiotensin system. It does not act by itself but through a receptor in the cell membrane — the AT1 receptor. Two places matter here:
- The smooth muscle of the vessel wall. There the occupied receptor frees the messenger IP3 via Gq and phospholipase C; calcium rises inside the cell, and the muscle cell shortens.
- The adrenal cortex. There the same path leads the outer cell layer to form the hormone aldosterone and release it into the blood.
- Aldosterone regulates in the kidney how much sodium is reclaimed and how much potassium is released.
- Candesartan cilexetil is the ester precursor. The ester group is cleaved off already during the passage out of the bowel; what reaches the blood is the active form.
Candesartan lays itself into the same pocket of the AT1 receptor into which angiotensin II otherwise reaches, and comes away from it only slowly. It thus acts at the other end of the same axis than an ACE inhibitor does: angiotensin II still arises — the label even describes a rise of renin and angiotensin II — it merely no longer finds its receptor free. The enzyme ACE itself remains untouched; bradykinin is therefore still taken apart as before.
What this means in an individual case depends on many things and belongs in a conversation with a doctor or health practitioner.
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The pathway step by step
Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.
- Candesartan cilexetil → Uptake in the gut wall
Already during the passage out of the bowel, esterases cleave off the ester group. The label describes the precursor as being fully converted to the active form in the process; it reaches the blood already converted. Only part of it reaches the blood. Source 6, 9↑ supplies The esterases of the gut wall release the active substance. Only part of the precursor reaches the blood in the process, and that part arrives there already as candesartan.
established physiology Source 9, 6
⚖ When the balance tips
too much — If a lot passes through the gut wall, candesartan in the blood rises; because conversion there is already complete, it adds nothing beyond what is absorbed.
too little — If little passes through the gut wall, little candesartan reaches the blood, and little active substance is present at the receptor.
established physiology · Source 9, 6
- Uptake in the gut wall → Candesartan esterases of the gut
Candesartan is the form that acts at the receptor. It carries an acid group and a tetrazole ring; both reach into the binding pocket of the AT1 receptor and come away from it only slowly. Even a lot of angiotensin II hardly displaces it. Source 3, 6↓ depletes Candesartan keeps angiotensin II away from the AT1 receptor and comes away so slowly that even a lot of angiotensin II hardly displaces it. In cell experiments it also dampens the receptor's own activity.
observed in studies Source 3, 6
⚖ When the balance tips
too much — If a lot of candesartan is present, almost all AT1 receptors are occupied; the vessels widen, and the adrenal gland releases less aldosterone.
too little — If little candesartan is present, many receptors remain free; angiotensin II narrows the vessels and stimulates aldosterone release as usual.
established physiology · Source 9, 1
- Candesartan → Travelling in the blood
In the blood candesartan hangs almost entirely on proteins. It is hardly remodelled; the label names kidney and bile as the routes by which it leaves the body again. Only the free part reaches the receptor. Source 6, 9↑ supplies Bound to protein, candesartan is distributed with the blood; only the free part reaches the receptor. It leaves the body largely unchanged via the kidney and bile.
established physiology Source 6, 9
⚖ When the balance tips
too much — If a lot of candesartan is present in the blood, for example because the kidney excretes more slowly, the free share is larger too, and more receptors are occupied.
too little — If little is present in the blood, the free share is very small, because almost all of it is bound to proteins; little then arrives at the receptor.
established physiology · Source 6, 9
- Smooth muscle cell → Calcium in the cell Gq, phospholipase C
The switched-on receptor sets the G protein Gq going. Phospholipase C then splits a fat of the cell membrane and frees IP3; IP3 opens the calcium stores, and calcium rises inside the cell. This is the signal to contract. Source 2, 8↑ supplies The rise in calcium is the signal to contract. It is the rise that is read; at rest the cell keeps free calcium very low.
established physiology Source 8, 2
⚖ When the balance tips
too much — If a lot of calcium rises, the muscle cell contracts strongly; pumps return it to the store and out of the cell, using ATP.
too little — If little calcium rises, the contractile apparatus of the muscle cell stays at rest, and the cell remains relaxed.
established physiology · Source 8
- Calcium in the cell → Muscle cell contracts
The rise of calcium sets the contractile apparatus of the muscle cell going. The cell shortens, and the diameter of the vessel becomes smaller. The resistance in the circulation rises. Source 8, 1↑ supplies If many muscle cells contract, the vessel narrows, and the resistance against which the heart pumps rises.
established physiology Source 1, 8
⚖ When the balance tips
too much — If the vessels contract strongly, blood pressure rises, and the heart pumps against more resistance.
too little — If they contract little, the vessels are wider, the resistance lower and blood pressure lower.
established physiology · Source 1
- Angiotensinogen → Angiotensin I Renin
Renin from the kidney cuts a piece of ten amino acids off angiotensinogen: angiotensin I. This chain does not yet bind to either receptor. Only ACE turns it into the active substance. Source 1↑ supplies Angiotensin I is itself hardly active. It is the starting material from which ACE makes angiotensin II.
established physiology Source 1
⚖ When the balance tips
too much — If angiotensin I rises, for example because the kidney releases more renin when receptors are occupied, more angiotensin II also forms via ACE.
too little — If little angiotensin I is present, ACE has little starting material, and little angiotensin II forms.
established physiology · Source 1, 9
- Angiotensin I → Angiotensin II ACE · zinc in the centre, chloride
ACE cleaves the last two amino acids off angiotensin I. What remains is angiotensin II. It binds at the AT1 receptor and makes the smooth muscle of the vessels narrower. It also stimulates the release of aldosterone. Source 1, 2, 9↑ supplies Angiotensin II narrows the vessels and stimulates the release of aldosterone. In this way it maintains blood pressure and salt balance.
established physiology Source 1, 2
⚖ When the balance tips
too much — If a lot of angiotensin II is present, the vessels narrow and more aldosterone is released; if candesartan occupies the receptors, this rise largely comes to nothing.
too little — If little angiotensin II is present, the vessels contract less, and the adrenal gland releases less aldosterone.
established physiology · Source 1, 9
- Angiotensin II → Aldosterone AT1 receptor
Angiotensin II also binds at the AT1 receptor of the adrenal cortex. The cortex then releases the hormone aldosterone into the blood. Sodium and water then stay in the body. Source 1, 4, 9↑ supplies Aldosterone makes the kidney retain sodium, and water with it, and release potassium. In this way it helps determine how full the vessels are.
established physiology Source 4, 1
⚖ When the balance tips
too much — If a lot of aldosterone is present, the collecting duct reclaims more sodium, water follows, and more potassium leaves in the urine.
too little — If little aldosterone is present, for example with occupied AT1 receptors, more sodium leaves the body, and potassium is released to a lesser extent.
established physiology · Source 4, 5, 9
- Aldosterone → Sodium and potassium ENaC, Na-K pump
Aldosterone makes the kidney reclaim more sodium in the collecting duct and release more potassium. With the receptor occupied both shift; the label describes only a small change of serum potassium. Water follows the sodium. Source 5, 9↑ supplies Through sodium the kidney keeps water in the body and thus the filling of the vessels; through potassium it sets the voltage across cell walls.
established physiology Source 5, 1
⚖ When the balance tips
too much — If the kidney reclaims a lot of sodium, water follows, and the vessels are fuller; in exchange, more potassium leaves in the urine.
too little — If it reclaims little sodium, for example with little aldosterone, more sodium leaves with water, and potassium tends to stay in the blood; the label describes only a small change.
established physiology · Source 5, 9
Further stations
- Candesartan cilexetil — ester precursor, swallowed
Candesartan cilexetil is swallowed as a tablet. It is not yet the form that acts at the receptor but a precursor: at one place on the molecule sits an ester group that has to be cleaved off first. Only then does it act. Source 6, 9↑ supplies The precursor itself is inactive at the receptor. The ester group helps the substance through the gut wall, where the active substance is only then released.
established physiology Source 6, 9
⚖ When the balance tips
too much — If a lot of precursor arrives, it too is fully converted during passage; more candesartan then appears in the blood, not the precursor.
too little — If little precursor arrives, little candesartan forms, and little active substance is present at the receptor.
established physiology · Source 6, 9
- AT1 receptor — receptor in the cell membrane
The AT1 receptor crosses the cell membrane in seven turns. Angiotensin II lays itself into its pocket and switches it on. Candesartan occupies the same pocket but switches nothing on. The signal of angiotensin II then does not occur. Source 2, 3, 9↑ supplies The switched-on AT1 receptor carries the signal of angiotensin II into the cell: vessels narrow, and the adrenal gland releases aldosterone. If candesartan occupies it, this signal does not occur.
established physiology Source 2, 9
⚖ When the balance tips
too much — If the receptor is often switched on, the vessels stay narrow, and a lot of aldosterone keeps sodium and water in the body.
too little — If the receptor is hardly switched on because candesartan occupies it, the vessels widen; the kidney then releases more renin, and angiotensin I and II rise in the blood.
established physiology · Source 2, 1, 9
- Smooth muscle cell — carries the AT1 receptor
In the wall of the vessels lies a layer of smooth muscle. Its cells carry the AT1 receptor on their surface; through it the signal of angiotensin II reaches them. It helps set how wide the vessel is. Source 1, 2↑ supplies The vascular muscle cell turns the signal into tension. How narrow it sets the vessel helps determine the resistance in the circulation and thus blood pressure.
established physiology Source 1, 2
⚖ When the balance tips
too much — If the cell receives a lot of signal from angiotensin II, it tenses more strongly; the vessel narrows, and blood pressure rises.
too little — If it receives little signal because the receptor is occupied, it relaxes, and the vessel widens.
established physiology · Source 1, 2
- Angiotensinogen — protein from the liver
The liver releases angiotensinogen into the blood continuously. It is the common starting chain for the steps that follow. Usually the amount of renin sets the pace. Source 1↑ supplies Angiotensinogen is the store from which renin cuts. It is plentiful in the blood; usually the amount of renin determines how fast angiotensin forms.
established physiology Source 1
⚖ When the balance tips
too much — If a lot of angiotensinogen is present, renin can split off more angiotensin I; the pace, however, is usually set by renin.
too little — If little angiotensinogen is present, less angiotensin I forms even with a lot of renin.
established physiology · Source 1
What the AT1 receptor governs
- Sodium — Aldosterone governs how much sodium the kidney reclaims in the collecting duct; water follows the sodium Source 1, 5
- Potassium — Aldosterone governs the release of potassium in the collecting duct of the kidney; less aldosterone shifts it Source 5, 9
- Calcium — Rises in the vascular muscle cell when the AT1 receptor opens the calcium stores via IP3; the cell then contracts Source 2, 8
What takes part in these steps
- Inositol — Building block of PIP2, from which phospholipase C splits off IP3 after the receptor signal; IP3 opens the stores Source 8
- Magnesium — Forms with ATP the complex that the sodium-potassium pump in the collecting duct turns over; without it the pump stalls Source 7
- ATP — Energy source of the sodium-potassium pump through which aldosterone moves sodium and potassium Source 7
What the prescribing information states
Placebo-controlled trials with 2,350 adults on candesartan and 1,027 on placebo. The prescribing information lists here the reactions that occurred in at least 1 of 100 participants and were more frequent on candesartan than on placebo. There is no column for an active comparator — at this place the prescribing information carries no third group.
How to read the table: what matters is the comparison within the row, not the single figure. Three points belong with it — for the first five rows the prescribing information selected only those reactions that were more frequent on candesartan than on placebo; anything that occurred equally often, or more often on placebo, does not appear there at all. The last row comes from the same section and ran the other way. And a third column with an active comparator is missing because the prescribing information carries none at this place.
| Candesartan (2,350) | Placebo (1,027) | |
|---|---|---|
| Upper respiratory tract infection | 6% | 4% |
| Dizziness | 4% | 3% |
| Back pain | 3% | 2% |
| Pharyngitis | 2% | 1% |
| Rhinitis | 2% | 1% |
| Stopped because of adverse events | 2.4% | 3.4% |
Further reactions have been reported after approval. The prescribing information notes that neither a frequency nor a causal relationship can be derived from such reports; they are therefore not listed here.
Sources
- Triebel H, Castrop H. The renin angiotensin aldosterone system. Pflugers Arch 2024 · PubMed 38233636
- Eckenstaler R, Sandori J, Gekle M et al. Angiotensin II receptor type 1 - An update on structure, expression and pathology. Biochem Pharmacol 2021 · PubMed 34252409
- Van Liefde I, Vauquelin G. Sartan-AT1 receptor interactions: in vitro evidence for insurmountable antagonism and inverse agonism. Mol Cell Endocrinol 2009 · PubMed 18620019
- Bollag WB. Regulation of aldosterone synthesis and secretion. Compr Physiol 2014 · PubMed 24944029
- Palmer BF. Regulation of Potassium Homeostasis. Clin J Am Soc Nephrol 2015 · PubMed 24721891
- Gleiter CH, Mörike KE. Clinical pharmacokinetics of candesartan. Clin Pharmacokinet 2002 · PubMed 11825094
- Clausen MV, Hilbers F, Poulsen H. The Structure and Function of the Na,K-ATPase Isoforms in Health and Disease. Front Physiol 2017 · PubMed 28634454
- Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 2003 · PubMed 12838335
- US prescribing information (United States): Candesartan Cilexetil Tablets, DailyMed, version of 9 Sept 2026, sections 11 Description, 12.1 Mechanism of Action, 12.2 Pharmacodynamics and 12.3 Pharmacokinetics · Prescribing information
- US prescribing information (United States): Candesartan Cilexetil Tablets, DailyMed, version of 9 Sept 2026, sections 6.1 Clinical Studies Experience and 6.2 Postmarketing Experience · Prescribing information
Related pathways
- Ramipril — angiotensinogen
- Amlodipine — calcium in the cell
As of 2026-09-25. Draft, written by Claude to schema v2; sources checked in PubMed; expert approval pending
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