Prostaglandin inhibitors alter loop segment chloride uptake during furosemide diuresis.
Prostaglandin synthesis inhibition antagonizes the chloruretic effect of furosemide. To identify the site of this interaction, cortical micropuncture was performed in furosemide-treated rats during meclofenamate or indomethacin infusion. Control rats received the vehicle for prostaglandin synthesis inhibition. The fractional excretion of chloride decreased from 10.6 +/- 1.0% in control rats to 6.5 +/- 0.93% in indomethacin-treated rats (P less than 0.01) and to 5.7 +/- 0.7% in meclofenamate-treated rats (P less than 0.001). Mean arterial pressure, inulin clearance, renal blood flow, and single nephron glomerular filtration rate were not different among the groups. Chloride delivery out of the late proximal tubule was also not different among the groups. Early distal tubule chloride delivery was greater (P less than 0.001) in control rats than in either prostaglandin-inhibited group. Late distal chloride delivery was also greater in control rats. Calculated loop segment chloride uptake was 9 +/- 2% in furosemide-treated control rats but 18 +/- 2% in both indomethacin- and meclofenamate-treated rats (P less than 0.05). Distal tubule chloride uptake was greater in control than in prostaglandin-inhibited rats. Thus, the attenuated chloruretic response to furosemide observed in indomethacin- or meclofenamate-treated animals may in part result from increased chloride uptake in the loop segment of superficial nephrons.
D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D004231:Diuresis / Q000187:drug effects*; D004573:Electrolytes / Q000652:urine; D005665:Furosemide / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007686:Kidney Tubules, Distal / Q000378:metabolism; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D014556:Urine; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D002712:Chlorides; D004573:Electrolytes; D062367:ortho-Aminobenzoates; D008469:Meclofenamic Acid; D005665:Furosemide; D007213:Indomethacin