Antidiuretic action of vasopressin: quantitative aspects and interaction between V1a and V2 receptor-mediated effects

(1) Vasopressin (VP), or antidiuretic hormone, is secreted in response to e ither increases in plasma osmolality (very sensitive stimulus) or to decrea ses in plasma volume (less sensitive stimulus). Its normal plasma level is very low (about 1 pg/ml, i.e. 10(-12) M), close to the detection limit of p resent immunoassays, and distinct antidiuretic effects are observed after i nfusion of small undetectable amounts of VP. (2) This antidiuretic action r esults from three main effects of VP on principal cells of the collecting d uct (CD) mediated by occupancy of peritubular V2 receptors. (i) Increase in water permeability along the entire CD (via AQP2). (ii) Increase in urea p ermeability in only the terminal inner medullary CD (via UT-Al). (iii) Stim ulation of sodium reabsorption, mainly in the cortical and outer medullary CD (via ENaC). VP also acts on medullary vasculature (V1a receptors) to red uce blood flow to inner medulla without affecting blood flow to outer medul la. Besides these actions, all concurring to increase urine osmolality in d ifferent and additive ways, other V-P effects, probably exerted through Vla receptors located on luminal membrane, tend to limit the antidiuretic effe cts of the hormone. They induce the formation of prostaglandins which reduc e V2-dependent cAMP accumulation in these cells and thus partially inhibit all three V2 effects. (3) Because urine is first diluted along the nephron before being concentrated in the medulla, VP is required, not only for urin e concentration, but first for re-equilibration of tubular fluid osmolality with plasma osmolality, a step taking place in the renal cortex, and achie ved through the reabsorption of large quantities of water (more than what i s subsequently reabsorbed in the medulla to concentrate urine). Accordingly , VP effects on urine flow-rate are not linear. Small changes in plasma VP in the low range of urine osmolality will induce wide changes in urinary fl ow-rate, whereas in the upper range of urine osmolality larger changes in p lasma VP induce much more limited further reduction in urine flow-rate. (4) Most likely, the different effects of VP require different levels of VP co ncentration to occur and are thus recruited successively with progressive r ise in VP secretion, (C) 2001 Elsevier Science BY All rights reserved.