Antidiuretic Hormone

Synthesis and Storage

ADH is synthesised in the supraoptic and paraventricular nuclei in the hypothalamus. It is then transported via the nerve axon to the posterior pituitary gland (or neurohypophysis), forming the hypothalamic-hypophyseal tract. ADH is then stored in the posterior pituitary gland until it is ready to be secreted into the circulation.

Release of ADH

The release of ADH is controlled by several factors, the two most influential being changes in plasma osmolality, and volume status. Other factors such as exercise, angiotensin II, and emotional states such as pain also promote ADH release.

ADH secretion is inhibited by atrial natriuretic peptide (ANP), which is released during atrial stretch in response to increased blood pressure, as well as alcohol and certain medications.

Plasma osmolality

Osmoreceptors are located in hypothalamus, specifically in the organum vasculosum of the lamina terminalis (OVLT) and the subfornical organ. Both are sensory circumventricular organs as they lack a blood-brain barrier. This allows them to directly detect changes in systemic plasma osmolality (which is directly proportional to osmotic pressure).

When osmolality increases, water exits osmoreceptors by osmosis down its concentration gradient into the plasma. As water leaves, osmoreceptor cell shrinkage triggers afferent signals from the hypothalamus to the posterior pituitary gland, causing ADH release. Thus, hypothalamic osmoreceptors respond to changes in plasma osmolality by adjusting ADH secretion.

Plasma osmolality is also affected by the total body plasma volume – a fall in plasma volume causes an increase in the plasma sodium (Na⁺) concentration, increasing osmolality. Thus, osmoreceptors also respond to changes in volume status.

When total body volume increases, reducing plasma osmolality, water moves down its concentration gradient from the plasma, into osmoreceptors. The subsequent expansion of osmoreceptor cells triggers afferent signals to be sent from the hypothalamus to the posterior pituitary gland, decreasing ADH release.

Volume Status

Baroreceptors also respond to changes in volume status to affect ADH release. They are located in the left atrium, carotid artery and aortic arch and detect changes in arterial blood pressure. Arterial blood pressure is affected by circulating blood volume.

A reduction in blood pressure is relayed via baroreceptors to the vagus nerve, which sends afferent signals that directly stimulate ADH release from the posterior pituitary. Conversely, in a hypervolemic state, blood pressure increases and ADH secretion is reduced.

Action of ADH

The main action of ADH in the kidney is to regulate the volume and osmolality of urine. It acts in the distal convoluted tubule (DCT) and collecting duct (CD) to achieve this.

When plasma osmolality and ADH secretion increases, ADH binds to vasopressin 2 (V2 receptors, a G-protein coupled receptor) on principal cells in the DCT and CD. This promotes the transcription and insertion of aquaporin–2 channels into the apical membrane of these cells. Consequently, the permeability of the DCT and CD cells to water increases.

This allows water to move down its concentration gradient from the lumen of the nephron back into the bloodstream. This reabsorption of water increases total blood volume, thereby reducing and normalising plasma osmolality whilst concentrating the urine.

OpenStax College (CC BY 3.0 [https://creativecommons.org/licenses/by/3.0/deed.en]), via Wikimedia Commons

Figure 1
Mechanism of water reabsorption in the kidney

When plasma osmolality decreases and ADH release is reduced, fewer aquaporin-2 channels are inserted into the apical membrane of the DCT and CD cells. The subsequent reduction in water reabsorption, reduces blood volume and increases and normalising plasma osmolality whilst producing a dilute urine.

In high concentrations, ADH also binds V1 receptors on vascular smooth muscle cells. This causes vasoconstriction, increasing peripheral vascular resistance and therefore blood pressure. This is useful in restoring blood pressure during hypovolemic shock.

Created in BioRender

Figure 2
Regulation of the ADH axis