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Arginine Vasopressin Mechanism of Action

Arginine vasopressin, vasopressin, or Anti Diuretic Hormone (ADH) is a peptide hormone which is synthesized in the supraoptoic nucleus of the hypothalamus. It is transported down the infundibulum and is stored in secretory vesicles in the posterior pituitary. Control of ADH release is regulated by volume status and plasma osmolality. Either hypovolemia or hyperosmolarity stimulates release of the hormone, which circulates in the blood until it reaches its target receptor. There are several other factors that have some regulatory effect on vasopressin release. Ethanol may decrease the release of vasopressin leading to increased diuresis. Angiotensin II, when created in the lungs via angiotensin converting enzyme, also stimulates vasopressin release from the posterior hypothalamus.

The primary location of effect is the kidney, specifically the collecting ducts. Here, V2 receptor activation leads to the creation aquaporin channels via a cAMP process. This allows for the passive resorption of water from a more dilute urine back into the blood stream. Vasopressin also leads to increased sodium absorption in the ascending loop of Henle, which further increases the osmotic gradient for resorption in the collecting ducts as mentioned above. Vasopressin can also lead to increased thirst, driving the patient to increase water consumption in an effect to increase intravascular volume.

Vasopressin also has a profound effect in the vascular smooth muscle bed. Activation of the V1 receptor leads to IP3 activation and smooth muscle vasoconstriction, which in turn leads to an increase in systemic vascular resistance, blood pressure, and perfusion. Interestingly, V1 receptors are not commonly located in the pulmonary vasculature making vasopressin a good option for vasoconstriction in patients with pulmonary hypertension.

Updated definition 2020:

MOA: stimulates the expression of a water channel protein, aquaporin-2, in the cell membranes of the cells in the medullary collecting tubule. This renders the luminal membrane permeable to water which in turn allows water to be osmotically drawn out of the collecting tubule and be re-absorbed into circulation. This creates concentrated urine (up to 1400 mOsm/L).

Other References

  1. Keys to the Cart: December 1, 2019 Link