Vasopressin / Antidiuretic Hormone (ADH)

Learning Objectives


  • General objective:

    • Understand the relationship between higher centres, the hypothalamus, posterior pituitary and the roles of the posterior pituitary hormones.

  • Specific objectives:

    • Understand roles of vasopressin and clinical implications


Vasopressin (Antidiuretic Hormone, ADH) Action


Major Function: Vasopressin, also known as antidiuretic hormone (ADH), is essential for water balance and cardiovascular regulation. Its main roles are to:

  • Promote water reabsorption in the kidney collecting ducts.

  • Maintain blood pressure and blood volume.

  • Regulate plasma osmolarity.


Site of Action - Collecting Duct: The collecting duct lumen is lined by epithelial cells, with V2 receptors for vasopressin located on the basolateral membrane. 


Molecular Mechanism of Action:

  • Vasopressin Release: Vasopressin is secreted from the posterior pituitary into the circulation in response to stimuli such as dehydration or increased plasma osmolarity.

  • Binding to Receptors: It binds to V2 receptors on the basolateral side of collecting duct epithelial cells.

  • Intracellular Signalling: Receptor activation increases intracellular cAMP and calcium levels, initiating downstream signalling.

  • Aquaporin-2 Mobilisation: Vesicles containing aquaporin-2 (AQP2) translocate to the apical membrane, inserting channels that increase water permeability.

  • Water Movement: Water enters epithelial cells through AQP2 and exits via aquaporin-3 (AQP3) and aquaporin-4 (AQP4) channels on the basolateral side. 

    • Water moves osmotically from dilute urine into concentrated plasma, down its concentration gradient.


Outcome: The result of vasopressin action is enhanced water reabsorption into the blood, leading to concentrated urine and maintenance of plasma osmolarity, blood volume, and blood pressure.



Regulation of Vasopressin (ADH) Release


Primary Driver - Plasma Osmolarity: The most important determinant of vasopressin release is plasma osmolarity, with a threshold of 280–290 mOsm/L. 

  • Hypothalamic Osmoreceptors: Osmolarity is detected by hypothalamic osmoreceptors located in the vascular organ of the lamina terminalis (OVLT). 

  • Vasopressin Release: When plasma osmolarity rises above this threshold, the osmoreceptors stimulate magnocellular neurons in the supraoptic nucleus, leading to vasopressin release from the posterior pituitary.


Effect on Osmolarity: Once released, vasopressin increases aquaporin-2 insertion into the apical membranes of collecting duct epithelial cells, enhancing water reabsorption from urine into blood. 

  • This decreases plasma osmolarity and restores homeostasis.


Experimental Evidence: Animal studies provide direct evidence of osmotic regulation. In rat models, administration of hypertonic saline produces a rapid and significant rise in plasma vasopressin, whereas isotonic saline has no significant effect on vasopressin levels.



Secondary Drivers of Vasopressin Release:

  • Hypovolemia (Low Blood Volume): 

    • Atrial Stretch Receptors: When blood volume falls due to reduced plasma water, atrial stretch receptors detect the decrease. 

    • Vasopressin Release: This stimulates vasopressin secretion, which increases water retention to help restore circulating volume.

  • Hypotension (Low Blood Pressure): 

    • Baroreceptors: A fall in blood pressure is detected by baroreceptors located in the carotid sinus and the aortic arch. 

    • Vasopressin Release: This also stimulates vasopressin release, conserving water and expanding plasma volume to restore pressure.



Summary of Regulatory Inputs:

  • Increased Plasma Osmolarity → Detected by hypothalamic osmoreceptors → Vasopressin release.

  • Decreased Blood Volume → Detected by atrial stretch receptors → Vasopressin release.

  • Decreased Blood Pressure → Detected by carotid and aortic baroreceptors → Vasopressin release.


Clinical Aspects of Vasopressin


Diabetes Insipidus (DI): Diabetes insipidus is characterised by polyuria (excessive urine output) and increased frequency of urination due to impaired renal water reabsorption.

  • Central Diabetes Insipidus: Central DI is caused by a deficiency of vasopressin production from the hypothalamus or posterior pituitary. 

    • Treatment: It is treated with desmopressin (DDAVP), a synthetic analogue of vasopressin that restores water reabsorption by acting on functional V2 receptors in the kidney.

  • Nephrogenic Diabetes Insipidus: Nephrogenic DI results from non-functional vasopressin receptors in the collecting ducts, rendering the kidneys unresponsive to ADH. 

    • Treatment: In this condition, desmopressin is ineffective because the defect lies at the receptor or renal signalling level. Management strategies include a low-solute diet (reduced salt and protein intake) to lower plasma osmolarity, use of thiazide diuretics, and ensuring adequate hydration.


Nocturnal Enuresis (Bedwetting): 

  • In normal children, maturation of the HPA axis increases vasopressin secretion during sleep, reducing nocturnal urine production. 

  • In some children, this maturation is delayed, resulting in persistent nocturnal enuresis into adolescence.


Treatment of Nocturnal Enuresis (Bedwetting): Intranasal desmopressin has been used to reduce nocturnal urine output. 

  • However, its paediatric use has been restricted because of rare but fatal cases of hyponatremia-induced seizures. 

  • Desmopressin remains available for adult use.


Vasopressin and the Renin–Angiotensin–Aldosterone Pathway (RAAS)


Low Blood Pressure and RAAS Activation: 

  • RAAS Activation: When blood pressure falls, the RAAS pathway is activated by both indirect and direct mechanisms. 

    • Indirect: Indirectly, reduced glomerular filtration rate (GFR) decreases sodium chloride delivery to the macula densa, which signals the granular cells of the afferent arteriole to secrete renin. 

    • Direct: Directly, reduced perfusion pressure in the afferent arteriole also stimulates renin release from granular cells.

  • Renin Effects due to RAAS Activation: 

    • Renin converts angiotensinogen (produced by the liver) into angiotensin I, which is then converted to angiotensin II by angiotensin-converting enzyme (ACE). 

    • Angiotensin II acts on multiple targets, including the hypothalamus, where it stimulates vasopressin release. 

    • Vasopressin promotes water reabsorption in the kidney collecting ducts, which increases blood volume and helps restore blood pressure.



High Blood Pressure and ANP: 

  • When blood pressure and blood volume rise, the atrial myocardium stretches, stimulating the release of atrial natriuretic peptide (ANP). 

  • ANP suppresses the RAAS pathway and also reduces vasopressin release, thereby decreasing water reabsorption. 

  • The net effect is natriuresis and diuresis, which lower blood volume and blood pressure.



Note: Low blood pressure → activates RAAS → angiotensin II → stimulates vasopressin release → water retention and restoration of blood pressure.


Note: High blood pressure → atrial stretch → ANP release → suppression of RAAS and vasopressin → increased water and salt excretion, lowering blood pressure.