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

Abstract

(1) Vasopressin (VP), or antidiuretic hormone, is secreted in response to either increases in plasma osmolality (very sensitive stimulus) or to decreases 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 present immunoassays, and distinct antidiuretic effects are observed after infusion of small undetectable amounts of VP. (2) This antidiuretic action results from three main effects of VP on principal cells of the collecting duct (CD) mediated by occupancy of peritubular V2 receptors. (i) Increase in water permeability along the entire CD (via AQP2). (ii) Increase in urea permeability in only the terminal inner medullary CD (via UT-A1). (iii) Stimulation of sodium reabsorption, mainly in the cortical and outer medullary CD (via ENaC). VP also acts on medullary vasculature (V1a receptors) to reduce blood flow to inner medulla without affecting blood flow to outer medulla. Besides these actions, all concurring to increase urine osmolality in different and additive ways, other VP effects, probably exerted through V1a receptors located on luminal membrane, tend to limit the antidiuretic effects of the hormone. They induce the formation of prostaglandins which reduce 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 urine concentration, but first for re-equilibration of tubular fluid osmolality with plasma osmolality, a step taking place in the renal cortex, and achieved through the reabsorption of large quantities of water (more than what is 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 flow-rate, whereas in the upper range of urine osmolality larger changes in plasma VP induce much more limited further reduction in urine flow-rate. (4) Most likely, the different effects of VP require different levels of VP concentration to occur and are thus recruited successively with progressive rise in VP secretion.

The genome of the model beetle and pest Tribolium castaneum

“…14), neither of which has been detected in any other sequenced insect 39 . Vasopressin in mammals is the major neurohormone stimulating water reabsorption in the kidneys 40 . Its presence in Tribolium may help the beetle to survive in very dry habitats.…”

Acute and chronic metabolic acidosis interferes with aquaporin-2 translocation in the rat kidney collecting ducts

“…1 Vasopressin increases osmotic water permeability in the collecting ducts and plays a key role in urine concentration. [2][3][4] AQP2 is a vasopressinsensitive water channel, which is present in the apical plasma membrane of the principal cells of the collecting ducts. [5][6][7] AQP3 and AQP4 are present in the basolateral membrane of the same cell but are insensitive to vasopressin.…”

Mild dehydration, vasopressin and the kidney: animal and human studies

“…Thus, during normal living conditions, vasopressin is constantly present in the blood, whereas the perception of thirst is intermittent. The sensitivity and threshold of the osmoregulatory systems show wide inter-individual variability in both humans and rats (Zerbe et al, 1991;Bankir, 2001). These individual differences are constant over prolonged periods and appear to be determined mainly by genetic factors (Zerbe et al, 1991).…”