The influence of prostaglandin E2 and indomethacin on the renal corticomedullary solute gradient in the rat.
The renal corticomedullary solute gradient and the urinary excretion of fluid and solute were determined during a saline infusion in anaesthetized and conscious rats. In the anaesthetized group the influence of PGE2 (100 ng min-1) given by a local renal infusion was investigated. In the conscious group (where prostaglandin synthesis does not contribute to renal blood flow) the effect of indomethacin (i.v. 10 mg kg-1) was determined. Following PGE2 infusion the corticomedullary gradient for sodium was depressed, equalizing the sodium concentration between the papilla tip and the final urine. Sodium output and urine flow were elevated, but both urinary and gradient changes could be dissociated from any increase in renal blood flow, assessed by PAH clearance. Following treatment with the prostaglandin synthetase inhibitor indomethacin in the conscious rat, the corticomedullary osmotic gradient was elevated while the urine flow was reduced. This increase in the gradient produced by indomethacin was, however, found to be independent of the decrease in urine flow. The results of the present experiments are consistent with the hypothesis that prostaglandin synthesis helps to determine the renal corticomedullary osmotic gradient, and does so by a mechanism unlikely to involve changes in renal blood flow or tubular flow rate: a permeability hypothesis is proposed.
D000818:Animals; D015232:Dinoprostone; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects*; D007679:Kidney Medulla / Q000187:drug effects*; D008297:Male; D009994:Osmolar Concentration; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
D011458:Prostaglandins E; D012964:Sodium; D015232:Dinoprostone; D007213:Indomethacin