Vasopressin

Vasopressin, or antidiuretic hormone, is a nonapeptide made in magnocellular paraventricular and supraoptic neurons and stored in the posterior pituitary. It differs from oxytocin at two of its nine positions. Three receptors divide its actions: V2 on the renal collecting duct is Gs-coupled and inserts aquaporin-2 channels apically to reabsorb water; V1a on vascular smooth muscle is Gq-coupled and vasoconstricts; V1b on corticotrophs potentiates ACTH release.

Release is governed by hypothalamic osmoreceptors and the response is steep, climbing once plasma osmolality passes roughly 280 to 285 milliosmoles per kilogram, well before thirst becomes urgent. Desmopressin is the receptor-selective analogue: substitutions at the first and eighth positions make it V2-selective, longer-acting and free of pressor effect, allowing its use in central diabetes insipidus and nocturnal enuresis. It also releases von Willebrand factor and factor VIII, giving it a haemostatic indication.

The receptor split is what makes vasopressin effectively two drugs in one molecule. Given for vasodilatory shock it acts as a V1a agonist and the antidiuresis is an unwanted extra; given for water conservation the vasoconstriction is the hazard. Terlipressin, a longer-acting analogue approved in the United States in 2022 for hepatorenal syndrome, carries the same tradeoff, with warnings about respiratory failure and ischaemia.

Native vasopressin is awkward to measure, unstable and largely platelet-bound, so copeptin - the C-terminal fragment released in equimolar amounts from the same precursor - serves as a stable surrogate, and stimulated copeptin testing has largely displaced the water deprivation test. The error that matters clinically is the mirror of the drug's purpose: V2 agonism without a matching fluid restriction risks dilutional hyponatraemia, the commonest serious harm from desmopressin.