The Effect of Thiazide, Amiloride and Hypertonic Saline on Urinary Biomarkers in Healthy Subjects (THAM)

• urinary biomarkers [ Time Frame: baseline, 0 hours and 1.5 hours after intervention ] [ Designated as safety issue: No ]
  Urinary epithelial sodium channels (ENaC), Sodium-Chloride transporters (NCC), Sodium-potassium-2chloride transporters (NKCC) and aquaporin2 channels (AQP2) before, during and after fluid infusion
  
  

• vaso active hormones [ Time Frame: baseline, 0 hours and 1.5 hours after intervention ] [ Designated as safety issue: No ]
  plasma concentrations of: renin, Angiotensin II, aldosterone, Vasopressin, ANP and BNP
  
  
• central blood pressure [ Time Frame: baseline, 0 hours and 1.5 hours after intervention ] [ Designated as safety issue: No ]
  measured by applanation-tonometry
  
  
• intracellular (ICV)- and extracellular volume (ECV) [ Time Frame: baseline, 0 hours and 1.5 hours after intervention ] [ Designated as safety issue: No ]
  change in ICV and EVC from baseline and after intervention measured in liters by body composition monitor (BCM)
  
  

1. Urinary biomarkers reflects the kidneys transport of sodium and water in the nephron.
2. Changes in the sodium-and water channel activity is induced by blocking the NCC channels with thiazide and ENaC channels with amiloride and by intervention with hypertonic NaCl The changes in sodium-and water channels are followed by changes in extracellular and intracellular fluids, central bloodpressure and the plasma concentration of vasoactive hormones.

The purpose of this study is to investigate the correlation between urinary biomarkers, changes in the activity of the sodium-and water channels, changes in the extra- and intracellular fluid compartments, central bloodpressure and the plasma concentration of Vasoactive hormones in healthy subjects.

Subjects will be examined on three examination days. Four days prior to the examination days the subjects will consume a standard diet based on amount of sodium and calories and randomized to treatment with either thiazide, amiloride or placebo twice daily for 5 days. On the examination days the subjects receive an infusion with hypertonic saline.

Renal function is measured by renal clearance of 51Cr-EDTA. Urinary biomarkers will be measured to evaluate the activity of sodium channels in the nephron, changes in fluid compartments are measured by body composition monitor. Central blood pressure is measured by sphygmocor.