Summary
Highlights
ADH, also known as antidiuretic hormone, is produced by neurons in the hypothalamus, specifically the supraoptic nucleus. Although produced in the hypothalamus, it is stored and secreted from the posterior pituitary gland in response to specific stimuli.
There are two main stimuli for ADH release: low blood pressure and high plasma osmolality. Low blood pressure leads to the production of Angiotensin II, which stimulates ADH release. High plasma osmolality, indicating hypertonic blood with low water concentration and high solute concentration, is detected by osmoreceptors in the hypothalamus, such as the organum vasculosum of Lamina terminalis and the subfornical organ, which then trigger ADH secretion.
ADH primarily acts on principal cells in the collecting ducts of the kidneys. It binds to vasopressin type 2 receptors, initiating an intracellular cascade involving G-proteins, adenylate cyclase, and cyclic AMP. This ultimately activates protein kinase A, which both promotes the synthesis of aquaporin 2 channels and facilitates their insertion into the cell membrane. These aquaporin 2 channels allow water to be reabsorbed from the urine filtrate back into the cells and then into the bloodstream, increasing plasma volume and blood pressure, and decreasing plasma osmolality.
In high concentrations, ADH can also act on smooth muscle cells in systemic blood vessels by binding to vasopressin type 1 receptors. This activates a GQ mechanism, increasing intracellular calcium and causing vasoconstriction. Vasoconstriction increases peripheral resistance, which in turn raises blood pressure.
A deficiency in ADH leads to diabetes insipidus, characterized by excessive urination (polyuria) and extreme thirst (polydipsia), as water is not reabsorbed and is lost in the urine. Conversely, excessive ADH production results in the syndrome of inappropriate ADH (SIADH) secretion. This condition causes excessive water retention, which dilutes the blood, leading to hyponatremia and potentially dangerous cerebral edema due to water leaking into the brain.