Effects of indomethacin on renal hemodynamics and on water and sodium excretion by the isolated dog kidney.
Blood-perfused isolated dog kidneys demonstrate steady increases in blood flow and in water and sodium excretion which could be attributed to the accumulation of renal prostaglandins in the perfusing blood. This hypothesis was tested by adding indomethacin, a potent inhibitor of prostaglandins synthesis, to the perfusing blood. Indomethacin completely prevented the vasodilation observed in control kidneys, without affecting glomerular filtration rate. Urine volume was not modified but sodium excretion was enhanced while the steady free water clearance increment observed in the control kidneys was depressed by indomethacin. The sum of sodium and free water clearances which, in the absence of antidiuretic hormone, constitutes an index of the part of the filtered load of solutes which escapes proximal tubular reabsorption, was not modified by indomethacin. Finally, indomethacin partially maintained the osmotic cortico-papillary gradient which was abolished after 2 hrs perfusion in control kidneys. These data suggest that prostaglandins accumulation in the blood is probably the major cause of the vasodilation taking place in isolated blood-perfused kidneys. This vasodilation does not account for decreased proximal reabsorption but partially explains the ADH-resistant diabetes insipidus developing in the isolated kidney. Moreover, indomethacin inhibits sodium reabsorption in the ascending limb of Henle's loop and increases water transport in the collecting duct.
D000818:Animals; D001783:Blood Flow Velocity; D004285:Dogs; D005919:Glomerular Filtration Rate; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D009994:Osmolar Concentration; D010477:Perfusion; D011188:Potassium / Q000097:blood / Q000652:urine; D012964:Sodium / Q000097:blood / Q000652:urine; D014882:Water-Electrolyte Balance
D012964:Sodium; D011188:Potassium; D007213:Indomethacin