In vitro and in vivo analysis of para-aminohippuric acid (PAH) transport: effect of indomethacin.
Effect of the prostaglandin synthesis inhibitor, indomethacin (indo) were studied on renal PAH transport (a) in renal cortical slices in vitro and (b) in anaesthetized dogs with various levels of plasma PAH concentrations (b1:PPAH less than 3 mg/dl and b2:PPAH V greater than 20 mg/dl] in vivo. It was found that: (a) indomethacin in concentrations of 0.4 and 4.0 micrograms/ml failed to influence PAH accumulation (S/M) and K or Na contents in renal cortical slices, whereas in a concentration of 40 micrograms/ml it potently decreased PAH accumulation (S/Mcontrol: 4.62 +/- 0.76, S/Mindo: 2.38 +/- 0.41; p less than 0.001). The oxygen uptake by tissue slices remained unaltered in the presence of indomethacin. (b1) Indomethacin in a dose of 4 mg/kg produced a pronounced antidiuresis and antinatriuresis with no change in GFR. PAH secretion was slightly reduced (TPAH control: 3.97 +/- 1.21; TPAH indo: 3.21 +/- 1.55 mg/min/100 g; p less than 0.01). (b2) Indomethacin appreciably decreased the secretory maximum of tubules (TmPAH control: 10.0 +/- 4.39; TmPAH indo: 4.95 +/-3.83 mg/min/100 g; p less than 0.001). Based on these results it is concluded that indomethacin, even when applied in the usual concentration, might partially block certain enzymes in the kidney.
D000618:Aminohippuric Acids / Q000097:blood*; D000818:Animals; D001692:Biological Transport; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006400:Hematocrit; D007213:Indomethacin / Q000494:pharmacology*; D007672:Kidney Cortex / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D010101:Oxygen Consumption; D011188:Potassium / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000097:blood; D010130:p-Aminohippuric Acid / Q000097:blood* / Q000378:metabolism
D000618:Aminohippuric Acids; D012964:Sodium; D011188:Potassium; D007213:Indomethacin; D010130:p-Aminohippuric Acid