To investigate the mechanisms behind the water- and sodium-retaining effect
s of growth hormone (GH), we studied the effect of GH on 1) water and sodiu
m homeostasis, 2) the renin-angiotensin-aldosterone system (RAAS), and 3) l
ithium clearance (C-Li) with and without concomitant prostaglandin (PG) syn
thesis inhibition with ibuprofen. GH administration for 6 days induced a si
gnificant increase in plasma renin, which was abolished by coadministration
of ibuprofen (mU.l(-1).24 h(-1): control: 22.4 +/- 4.3; GH: 37.7 +/- 8.8;
ibuprofen: 15.2 +/- 3.0; GH + ibuprofen: 19.7 +/- 2.5; ANOVA: P < 0.01). Co
mparable increments in extracellular volume were seen after 6-day treatment
with GH alone and in combination with ibuprofen [liters: control, 19.57 +/
- 0.92; GH, 20.80 +/- 1.00 (ANOVA: P < 0.0005); ibuprofen, 19.38 +/- 0.90;
GH + ibuprofen, 21.63 +/- 1.37 (ANOVA: P, 0.0005)]. Treatment with GH incre
ased CLi and changed the tubular handling of sodium and water. The absolute
distal sodium reabsorption was increased, and this was only partially coun
terbalanced by decreased reabsorption in the proximal tubules. The data dem
onstrate that GH-induced activation of the RAAS can be blocked by concomita
nt PG synthesis inhibition and that the tubular effects of GH include incre
ased distal nephron sodium and water reabsorption.