Renal prostaglandins and water balance: studies in normal volunteer subjects and in patients with central diabetes insipidus.
1. In six healthy volunteer subjects polydipsic water loading significantly increased urine volume from 1203 +/- 242 (SEM) to 5072 +/- 320 ml/24 h (P less than 0.001) with a significant decrease in urinary osmolality. This increase in urine volume by more than fourfold was associated with a slight increase in urinary excretion of prostaglandin E2 from 466 +/- 66 to 1017 +/- 174 pmol/24 h (P = 0.05). 2. In five patients with central diabetes insipidus mean urine volume of 10 838 +/- 107 ml/24 h was reduced to 1205 +/- 204 ml/24 h (P less than 0.001) by treatment with 1-desamino-8-arginine vasopressin (desamino-[Arg8]vasopressin; 15 microgram/day) with a significant rise in urinary osmolality. Desamino-[Arg8]vasopressin treatment was associated with a significant increase of suppressed urinary excretion of prostaglandin E2 (PGE2) in four of these patients from 246 +/- 66 to 2643 +/- 677 pmol/24 h (P less than 0.01). 3. Concomitant treatment with indomethacin in addition to desamino-[Arg8]vasopressin significantly suppressed urinary excretion of PGE2 and significantly increased urinary osmolality as compared with treatment with desamino-[Arg8]vasopressin alone. 4. Desamino-[Arg8]vasopressin significantly increased urinary excretion of adenosine 3':5'-cyclic monophosphate (cyclic AMP). However, there was no further change in urinary excretion of cyclic AMP during concomitant indomethacin treatment. 5. The results suggest that urine flow itself is not an important determinant of urinary PGE2 excretion. In patients with central diabetes insipidus the urinary concentrating response to desamino-[Arg8]vasopressin is enhanced during inhibition of prostaglandin synthesis without changes in urinary excretion of cyclic AMP.
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000242:Cyclic AMP / Q000652:urine; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D003919:Diabetes Insipidus / Q000188:drug therapy / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use; D007610:Kallikreins / Q000652:urine; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000652:urine; D012083:Renin / Q000097:blood; D014882:Water-Electrolyte Balance
D011453:Prostaglandins; D011458:Prostaglandins E; D000450:Aldosterone; D000242:Cyclic AMP; D007610:Kallikreins; D012083:Renin; D003894:Deamino Arginine Vasopressin; D007213:Indomethacin