Nephron site of effect of nonsteroidal anti-inflammatory drugs on solute excretion in humans.
Indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs) decrease solute excretion when administered acutely to normal subjects. We performed clearance studies during water loading of 10 normal volunteers and during hydropenia in eight additional subjects to determine the nephron site of this effect using indomethacin and carprofen as inhibitors of prostaglandin (PG) synthesis. Their administration decreased fractional excretion of sodium, chloride, and volume. During water loading, fractional clearance of free water decreased from 0.13 +/- 0.04 during the control study to 0.09 +/- 0.03 and 0.06 +/- 0.02 with indomethacin and carprofen, respectively. However, fractional delivery of solute to the dilution segment decreased in parallel such that free water clearance corrected for delivery did not change with either drug. In humans, therefore, the decrement in solute excretion that occurs with administration of NSAIDs occurs prior to the diluting segment. During hydropenia, free water reabsorption relative to osmolar clearance increased (P less than 0.01). In both studies, neither the marker of renal perfusion or of proximal nephron function changed with inhibition of PG synthesis. The data indicate that at the tubular level, NSAIDs increase solute reabsorption at the medullary segment of the thick ascending limb of the loop of Henle. Therefore, a physiologic role of renal prostaglandins at this nephron site is implied.
D000893:Anti-Inflammatory Agents; D001834:Body Water / Q000378:metabolism; D002227:Carbazoles; D006801:Humans; D007213:Indomethacin; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009399:Nephrons / Q000187:drug effects / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D002227:Carbazoles; C007005:carprofen; D007213:Indomethacin