ADH exerts multiple effects on the kidneys and cardiovascular system, which include the following:
- In collecting ducts, ADH binds to V2 receptors on the basolateral membrane of principal cells, initiating a signaling cascade that leads to apical insertion of aquaporin channels. The collecting duct becomes permeable to water, which is reabsorbed because of the high osmotic pressure generated by the solute concentrated in the medullary interstitium. Over the long term, ADH also increases transcription of aquaporin channels. Nephrogenic diabetes insipidus is a well-characterized condition in which there is dysfunction of ADH-mediated aquaporin insertion (see Plate 3-27).
- ADH increases the reabsorption of sodium and urea, which increases the solute concentration in the medullary interstitium. As a result, there is a larger gradient for water reabsorption. In the thick ascending limb, ADH up-regulates apical NKCC2 Na+/K+/2Cl− cotransporters and ROM-K channels. Over the long term, ADH also increases transcription of NKCC2 cotransporters. In the collecting duct, ADH up-regulates apical ENaC channels and inner medullary urea transporters. As water is reabsorbed in the cortical and outer medullary collecting duct, urea becomes increasingly concentrated in the tubular lumen. Once urea reaches the IMCD, it is reabsorbed along its chemical gradient into the interstitium.
- ADH exerts a pressor effect on vasa recta capillaries, which minimizes the drift of solute away from the medullary interstitium.
- ADH increases peripheral vascular resistance via the V1a receptor, an important effect in volume depletion states. As a result, ADH is a useful pressor hormone in vasodilatory states, such as septic shock. In addition, ADH may be given during cardiac resuscitation.
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