Antidiuretic hormone (ADH, vasopressin)

Also known as: ADH, vasopressin, arginine vasopressin, AVP

A nonapeptide made in the supraoptic and paraventricular nuclei and released from the posterior pituitary that conserves water by inserting aquaporin-2 into collecting ducts, and constricts arterioles at high concentrations.

Overview

ClassNonapeptide

ReceptorsV2 (Gs) kidney; V1a (Gq) vessels; V1b (Gq) pituitary

Half-life≈10–20 min

Urine osmolality range≈50–1200 mOsm/kg

ADH (arginine vasopressin) is synthesised as part of a precursor with neurophysin II and copeptin, transported down axons and stored in the posterior pituitary. Copeptin is released in equimolar amounts and is a stable laboratory surrogate for ADH.

Its principal action is on the V2 receptor (Gs–cAMP) of collecting-duct principal cells: PKA phosphorylates aquaporin-2 and drives insertion of AQP2-containing vesicles into the apical membrane, so water leaves the tubule down the osmotic gradient of the medullary interstitium (water then exits basolaterally through AQP3/4). ADH also increases urea permeability of the inner medullary collecting duct (UT-A1) and NaCl reabsorption in the thick ascending limb, both of which strengthen the medullary gradient. Urine osmolality can thus range from ≈50 mOsm/kg (no ADH) to ≈1200 mOsm/kg (maximal ADH).

V1a receptors (Gq) mediate vasoconstriction (important in haemorrhage and septic shock), platelet aggregation and hepatic glycogenolysis; V1b (V3) receptors on corticotrophs potentiate ACTH release. V2 stimulation of endothelium releases von Willebrand factor and factor VIII.

Location

Source: magnocellular neurons of the supraoptic (mainly) and paraventricular nuclei; released from the posterior pituitary. Targets: collecting-duct principal cells (V2), vascular smooth muscle (V1a), corticotrophs (V1b).

Function

Increases water reabsorption in the collecting ducts (concentrated urine, reduced plasma osmolality).

Constricts arterioles and raises blood pressure (V1a) in hypovolaemia.

Potentiates CRH-stimulated ACTH release.

Releases von Willebrand factor and factor VIII from endothelium.

Physiology

Class: nonapeptide (9 aa, with a disulfide ring). Receptors: V2 (Gs/cAMP), V1a and V1b (Gq/IP₃). Half-life ≈10–20 min. Release threshold ≈280–285 mOsm/kg; each 1 mOsm/kg rise increases plasma ADH by ≈0.4 pg/mL.

Regulation

Stimulated by raised plasma osmolality (OVLT osmoreceptors — most sensitive control), hypovolaemia/hypotension of ≥≈5–10 % (atrial and arterial baroreceptors — less sensitive but more powerful), angiotensin II, nausea and vomiting, pain, stress, hypoglycaemia, nicotine and opiates. Inhibited by low osmolality, volume expansion, ANP, alcohol and cold.

Clinical significance

Diabetes insipidus (AVP deficiency/resistance)

Lack of ADH (central) or renal resistance (nephrogenic: lithium, hypercalcaemia, hypokalaemia, V2/AQP2 mutations) → large volumes of dilute urine, thirst and risk of hypernatraemia if water intake is limited.

SIADH

Inappropriate ADH secretion → water retention and euvolaemic hyponatraemia with concentrated urine; causes include small-cell lung carcinoma, CNS and lung disease, and drugs.

Pharmacology

Desmopressin (selective V2 agonist) treats central DI, nocturnal enuresis, haemophilia A and von Willebrand disease. Vasopressin/terlipressin (V1) is used in septic shock, variceal bleeding and hepatorenal syndrome. Vaptans (tolvaptan, V2 antagonists) treat hyponatraemia and slow polycystic kidney disease.