Antidiuretic hormone

Antidiuretic hormone (ADH), or arginine vasopressin (AVP), is a peptide hormone produced by the hypothalamus, and stored in the posterior part of the pituitary gland. ADH acts on the kidneys, concentrating the urine by promoting the reabsorption of water from the cortical collecting duct.

Physiology

Control

ADH is activated by "water receptors" in both the extracellular fluid volume and the intracellular fluid volume. Ethanol and caffeine block the release of ADH from the posterior pituitary gland. The resulting decrease in water reabsorption in the kidneys leads to a higher volume of urine output.

In the extracellular fluid the activators are mainly baroreceptors in the veins, atria, and arterioles. In the intracellular fluid the activators are mainly osmoreceptors in the hypothalamus.

Actions

ADH acts on three different receptors, termed V1a, V1b and V2. The receptors are differently expressed in different tissues, and exert different actions:

• V1a - vasoconstriction, gluconeogenesis in the liver, platelet aggregation and release of factor VIII and von Willebrand factor.
• V1b - corticotropin secretion from the pituitary gland.
• V2 - control of free water reabsorption in the collecting ducts of the renal medulla. Activation of adenylate cyclase causes a release of aquaporin-2 channels into the luminal membrane of the cells lining the collecting duct. This allows water to be reabsorbed down an osmotic gradient, and so the urine is more concentrated.

Pharmacology

ADH is used therapeutically in various conditions, and its long-acting synthetic analogue desmopressin is used in conditions featuring low ADH, as well as for control of bleeding (in some forms of von Willebrand disease) and in extreme cases of bedwetting by children. Terlipressin and related analogues are used as vasocontrictors in certain conditions.

Vasopressin has also been implicated in playing a positive role in different kinds of memory formation, including delayed reflexes, image, short- and long-term memory, though the mechanism remains unknown. Thus, desmopressin has come to interest as a likely nootropic.

Demeclocycline, a tetracycline antibiotic, is sometimes used to block the action of ADH on the kidney in hyponatremia (low blood sodium levels) due to increased secretion of ADH (SIADH, see below), when fluid restriction has failed. A new class of medication (conivaptan, tolvaptan, relcovaptan, lixivaptan) acts by inhibiting the action of ADH on its receptors (V1 and V2), with tolvaptan acting on V1a and V2 and the remainder mainly on V1a.

Role in disease

Decreased ADH release leads to diabetes insipidus, a condition featuring hypernatremia (increased blood sodium content), polyuria (excess urine production) and thirst.

Raised ADH (syndrome of inappropriate antidiuretic hormone) and resultant hyponatremia occurs in brain diseases and conditions of the lungs. In the peri-operative period, the effects of surgical stress and some commonly used medications (e.g. opiates, syntocinon, anti-emetics) lead to a similar state of excess ADH secretion. This may cause mild hyponatraemia for several days.