Reversal of indomethacin-induced inhibition of tubuloglomerular feedback by prostaglandin infusion.
Experiments were performed in rats to study the effect of infusion of PGI2, PGE2, and PGF2 alpha on tubuloglomerular feedback responses (i.e. the change of SNGFR in response to a change of loop of Henle flow rate) in the presence and absence of simultaneous inhibition of endogenous PG synthesis with indomethacin. Infusion of PGI2 or PGE2 at rates that did not alter arterial blood pressure did not significantly modify the magnitude of feedback responses (PGI2 8.5 micrograms/hr, PGE2 85 micrograms/hr). Some inhibition of feedback responses was seen when PGI2 and PGE2 were administered at higher rates that were associated with a reduction of blood pressure (PGI2 20 micrograms/hr, PGE2 200 micrograms/hr). PGI2 (8.5 micrograms/hr) and PGE2 (85 micrograms/hr) largely prevented feedback inhibition induced by indomethacin. When given subsequent to indomethacin PGI2 and PGE2 restored feedback responsiveness almost to normal. In contrast, PGF2 alpha did not influence feedback inhibition caused by indomethacin. Infusion of PGI2 induced partial restoration of feedback responses in DOCA-salt treated animals in which the feedback system is virtually completely inactive. Our results indicate that availability of PGI2 or PGE2 is necessary for the normal operation of the tubuloglomerular feedback mechanism for control of nephron filtration rate.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000494:pharmacology; D015237:Dinoprost; D015232:Dinoprostone; D011464:Epoprostenol / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D007684:Kidney Tubules / Q000187:drug effects*; D008138:Loop of Henle / Q000187:drug effects; D008297:Male; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D003900:Desoxycorticosterone; D015237:Dinoprost; D011464:Epoprostenol; D015232:Dinoprostone; D007213:Indomethacin