Osmomediated natriuresis in humans: The role of vasopressin and tubular calcium sensing

Background. The aim was to investigate the unknown mechanism of osmomediated natriuresis. This is the phenomenon by which hypertonic saline (HS) produces a larger natriuresis than isotonic saline (IS), despite the same sodium content.Methods. Seven healthy volunteers first received HS and then IS (both 3.85 mmol sodiumkg). To investigate the role of calcium metabolism, four patients received HS, two with an activating mutation (ADH) and two with an inactivating mutation (FHH) of the calcium-sensing receptor (CaSR).Results. In healthy volunteers, HS produced mild hypernatraemia, a 4-fold rise in vasopressin (to 2.2 ± 0.85 pgmL) and a 3-fold rise in natriuresis compared with a 1.5-fold rise with IS (P = 0.002). This confirmed osmomediated natriuresis. HS caused calciuresis to increase 1.4-fold and then reduced it 1.4-fold, whereas IS failed to increase calciuresis and caused it to fall 3.7-fold (P = 0.05). Natriuresis and calciuresis in ADH patients were similar to healthy volunteers receiving HS, whereas a blunted response was seen in FHH patients. Patient vasopressin levels did not exceed 1.3 pgmL and changes from baseline were variable. In one FHH patient, a 3-fold rise in vasopressin did not prevent the blunted natriuresis and calciuresis. In one ADH patient, natriuresis and calciuresis were similar to healthy volunteers despite a 1.7-fold fall in vasopressin.Conclusions. Our data suggest that not only vasopressin (possibly via its V1a receptor), but also the CaSR (which is sensitive to high sodium concentrations) may play a role in osmomediated natriuresis. These results shed new light on osmomediated natriuresis and suggest roles for the CaSR beyond calcium regulation.

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