Vasoactive peptides

Angiotensin, natriuretic peptides, endothelin, vasopressin, substance P and CGRP: peptides that set vessel tone and salt balance, and their drugs.

Updated Nov 2, 2026

Several short peptides act as hormones or local signals that tighten or relax blood vessels and tell the kidney to keep or lose salt and water. Many cardiovascular drugs work by blocking the constrictor peptides (angiotensin II, endothelin, vasopressin) or by protecting the dilator ones (natriuretic peptides, bradykinin).

The renin–angiotensin–aldosterone system

Low kidney perfusion, low sodium delivery and sympathetic activity release renin, which cuts angiotensinogen to angiotensin I; ACE then makes angiotensin II. Drugs block every step.

ACE inhibitors (enalapril): less angiotensin II and more bradykinin, hence cough and angioedema
ARBs (losartan): block the AT1 receptor directly
Mineralocorticoid receptor antagonists (spironolactone): block aldosterone
All of them can raise potassium and harm the fetus; they are avoided in pregnancy

Natriuretic peptides and neprilysin

ANP comes from the atria and BNP mainly from the ventricles when they are stretched; BNP blood levels help diagnose heart failure. Both act through a receptor that makes cGMP. Sacubitril blocks neprilysin and so raises natriuretic peptides; because neprilysin also breaks down angiotensin II and bradykinin, it is always combined with an ARB (valsartan) and never with an ACE inhibitor. Nesiritide is a recombinant BNP.

Endothelin

Endothelin-1 is made by the endothelium and acts on ETA and ETB receptors. It is raised in pulmonary arterial hypertension. Antagonists such as bosentan relax pulmonary vessels; they can harm the liver and cause birth defects, so their use is tied to pregnancy prevention and liver test programmes.

Vasopressin

V1 (vessels): vasopressin and terlipressin raise blood pressure in vasodilatory shock or reduce portal pressure in variceal bleeding
V2 (kidney): desmopressin, a selective V2 agonist, treats central diabetes insipidus and some bleeding disorders; it can cause hyponatraemia
V2 antagonists (tolvaptan): raise free-water loss in some hyponatraemias; serum sodium must not rise too fast

Sensory peptides: substance P and CGRP

Substance P acts on NK1 receptors in pain and vomiting circuits; aprepitant and fosaprepitant block it to prevent chemotherapy-induced vomiting. Calcitonin gene-related peptide (CGRP) is released from trigeminal nerves during migraine and is a strong vasodilator; monoclonal antibodies against CGRP or its receptor (erenumab) and small-molecule «gepants» prevent or treat migraine.

Test yourself

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

Why is sacubitril combined with valsartan rather than with an ACE inhibitor?

Neprilysin and ACE both break down bradykinin; blocking both raises the risk of angioedema, so sacubitril is paired with an ARB.

Which vasopressin receptor does desmopressin act on, and what is the main risk?

The V2 receptor in the kidney collecting duct; it can cause water retention and hyponatraemia.

What two safety issues are linked to endothelin receptor antagonists?

Liver injury and teratogenicity (birth defects).

What do aprepitant and erenumab have in common?

Both block a sensory neuropeptide pathway: aprepitant blocks substance P at NK1 receptors (vomiting), erenumab blocks the CGRP receptor (migraine).

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Valsartan and Sacubitril: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Lisinopril: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026).

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