The Role of V2 Receptor Antagonists in the Treatment of Hyponatremia

Abstract

Under normal circumstances, there is a balance between water intake and water excretion such that plasma osmolality and the serum sodium(Na+) concentration remain relatively constant. The principal mechanism responsible for prevention of hyponatremia and hyposmolality is renal water excretion. In all hyponatremic patients, water intake exceeds renal water excretion. Excretion of water by the kidney is dependent on three factors. First, there must be adequate delivery of filtrate to the tip of the loop of Henle. Second, solute absorption in the ascending limb and the distal nephron must be preserved so that the tubular fluid will be diluted. Lastly, arginine vasopressin (AVP) levels must be low in the plasma. Of these three requirements for water excretion, the one which is most important in the genesis of hyponatremia is the failure to maximally suppress AVP levels. Given the central role of AVP in limiting renal water excretion, AVP receptor antagonists represent a physiologic and rational method to increase renal water excretion.