Main points on physiological basis underlying AVP-D and AVP-R avoidance

MechanismDescriptionReference(s)
AVP release and functionAVP is produced by the hypothalamus and released by the posterior pituitary in response to increased plasma osmolality or dehydration. It promotes water reabsorption in the kidneys, concentrating urine.[30, 31]
Countercurrent mechanismThe countercurrent multiplier in the loop of Henle and the exchanger in the vasa recta create a hyperosmotic gradient in the renal medulla, essential for water reabsorption in the presence of AVP.[49, 51]
Regulation of urine concentration and dilutionIn the presence of AVP, collecting ducts become permeable to water, allowing reabsorption and urine concentration. Without AVP, the ducts remain impermeable, leading to dilute urine.[52]
AVP receptor activationAVP binds to V2 receptors in the kidney’s collecting ducts, activating the cAMP-PKA pathway, which promotes water reabsorption. Proper receptor function prevents excessive water loss, as in AVP-D.[34, 35]
AQP-2 channelsAVP triggers the movement of AQP-2 water channels to the collecting duct cells’ apical membrane, allowing water reabsorption. Proper AQP-2 function protects against AVP-R caused by channel disruption.[56]
Maintenance of the medullary osmotic gradientThe countercurrent multiplier in the loop of Henle concentrates solutes, creating a gradient that facilitates water reabsorption under AVP influence. The exchanger helps preserve this gradient.[57]
Solute transportersNa+/K+/2Cl– co-transporters in the thick ascending limb of the loop of Henle establish the osmotic gradient, supporting urine concentration and preventing excessive water loss.[58]

AQP-2: aquaporin-2; AVP: arginine vasopressin; AVP-D: AVP deficiency; AVP-R: AVP resistance; cAMP-PKA: cyclic adenosine monophosphate-protein kinase A; V2: vasopressin 2