vasopressin
Summary
Vasopressin (antidiuretic hormone, ADH) is synthesized in the hypothalamus and released from the posterior pituitary in response to increased plasma osmolality or decreased blood volume/pressure. It acts on V2 receptors in the renal collecting duct to increase water reabsorption via aquaporin-2 channel insertion, and on V1 receptors in vascular smooth muscle to cause vasoconstriction. Clinically important in diabetes insipidus, SIADH, and as a pressor agent in septic shock/vasodilatory shock.
Detail
Vasopressin is a nonapeptide hormone synthesized in the supraoptic and paraventricular nuclei of the hypothalamus, transported down axons to the posterior pituitary (neurohypophysis) for storage and release. Osmoreceptors in the hypothalamus detect increases in plasma osmolality (>~280 mOsm/kg) and stimulate ADH release; baroreceptors in the carotid sinus/aortic arch and volume receptors in the atria also stimulate release in response to hypotension or hypovolemia (a more potent but less sensitive stimulus than osmolality). Nonosmotic stimuli include pain, nausea, and certain drugs.
Mechanism of action: ADH binds V2 receptors (Gs-coupled) on principal cells of the renal collecting duct, activating adenylate cyclase → increased cAMP → PKA-mediated insertion of aquaporin-2 channels into the apical membrane, increasing water permeability and reabsorption, producing concentrated urine. ADH also binds V1 receptors (Gq-coupled) on vascular smooth muscle, activating phospholipase C → IP3/DAG → increased intracellular calcium → vasoconstriction, particularly important at high (pharmacologic) concentrations. V1 receptors are also present on hepatocytes stimulating glycogenolysis.
Clinical correlations: - Central diabetes insipidus: deficient ADH production/release (due to trauma, tumor, surgery, idiopathic) causing polyuria and polydipsia with dilute urine; treated with desmopressin (DDAVP, a V2-selective agonist). - Nephrogenic diabetes insipidus: renal resistance to ADH (lithium toxicity, hypercalcemia, genetic AQP2 or V2 receptor mutations); does not respond to desmopressin. - SIADH (Syndrome of Inappropriate ADH secretion): excess ADH causing hyponatremia with euvolemia, concentrated urine despite low serum osmolality; causes include small cell lung cancer (ectopic ADH), CNS disorders, pulmonary disease, and drugs (SSRIs, carbamazepine); treated with fluid restriction, vasopressin receptor antagonists (vaptans), or demeclocycline. - Vasopressin is used therapeutically as a vasopressor in septic shock (refractory to catecholamines) and historically in cardiac arrest (ACLS, though removed from current guidelines) and to treat esophageal variceal bleeding via splanchnic vasoconstriction. - Desmopressin is also used in von Willebrand disease and hemophilia A to stimulate release of vWF and factor VIII from endothelial cells (via V2 receptors on endothelium).
Water deprivation test and hypertonic saline test are used to differentiate central DI, nephrogenic DI, and primary polydipsia.
Sources
- First Aid for the USMLE Step 1
- Guyton and Hall Textbook of Medical Physiology
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
- Harrison's Principles of Internal Medicine
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