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 sodium/kg). 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 pg/mL) 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 pg/mL 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.
Hoorn
Ewout J
EJ
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. ejhoorn@gmail.com
Zillikens
M Carola
MC
Pols
Huibert A P
HA
Danser
Alexander H Jan
AH
Boomsma
Frans
F
Zietse
Robert
R
D000328:Adult; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006706:Homeostasis; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis; D009994:Osmolar Concentration; D044169:Receptors, Calcium-Sensing / Q000502:physiology*; D017483:Receptors, Vasopressin / Q000502:physiology; D014667:Vasopressins / Q000502:physiology*
D044169:Receptors, Calcium-Sensing; D017483:Receptors, Vasopressin; D014667:Vasopressins; D002118:Calcium