The role of the prostaglandin system in the regulation of renal function in normal women.

The role of prostaglandins in the regulation of renal function was studied in seven healthy female volunteers taking a constant metabolic diet containing 59 meq of sodium and about 50 meq of potassium daily. Each subject underwent two renal clearance studies, during which vasopressin (priming dose, 200 mU; "sustainer," 200 mU/hour at 1 ml/min) was infused intravenously. The first clearance study served as the control; indomethacin (2 mg/kg/day) was given for seven days before the second clearance study to inhibit prostaglandin synthesis. Food and fluid were withheld for 12 hours before the studies. Urine was collected through an indwelling bladder catheter at 30 minute intervals. Glomerular filtration rate was estimated from inulin clearance and renal blood flow from para-aminohippurate (PAH) clearance. Indomethacin was associated with a significant increase in maximal urinary osmolality from 826 +/- 47 mosmol/kg H2) to 920 +/- 32 mosmol/kg H2O (P < 0.01). Minimal "free water" clearance was -1.40 +/- 0.02 ml/min before and -1.63 +/- 0.04 ml/min (P < 0.01) after the administration of indomethacin. Indomethacin did not affect urine flow, urinary sodium or potassium excretion, glomerular filtration rate or renal plasma flow. In addition, indomethacin did not affect the urinary excretion of cyclic adenosine monophosphate (AMP). Plasma arginine-vasopressin, measured in two subjects by radioimmunoassay, did not change with blockade of prostaglandin synthesis. It appears that prostaglandins antagonize the hydro-osmotic effect of antidiuretic hormone by an intrarenal mechanism, independent of changes in renal hemodynamics or cation excretion. This mechanism is probably mediated by an alteration in the water permeability of the collecting ducts. Since urinary cyclic AMP did not change during blockade of prostaglandin synthesis, whereas urinary osmolality increased, a change of vasopressin-dependent cyclic AMP production in the kidney was probably not reflected in urinary cyclic AMP.