Tubuloglomerular feedback in obstructive uropathy.
The tubuloglomerular feedback (TGF) mechanism was studied in rats with chronic partial ureteral occlusion (hydronephrosis) with the use of the stop-flow pressure techniques and measurements of single nephron glomerular filtration rate. In hydropenic conditions, TGF was normal in hydronephrotic kidneys, but TGF sensitivity and activity increased in response to extracellular volume expansion, which is the opposite of normal resetting. The increased sensitivity may be due to an increased production of thromboxane A2 in the hydronephrotic kidney, since both inhibition of thromboxane synthetase and blockade of thromboxane/prostaglandin endoperoxide receptors normalized the resetting during volume expansion. Pelvic pressure in hydronephrotic kidneys was low in hydropenia and increased moderately during volume expansion. Thromboxane synthesis inhibition before volume expansion allowed pelvic pressure to increase by more than 100% as compared with untreated hydronephrotics. Also, when pelvic pressure increases were prevented during volume expansion, TGF resetting was normalized. An increased thromboxane synthesis during volume expansion may be protective in hydronephrotic kidneys, in that TGF resets to a higher sensitivity to prevent increases in glomerular filtration rate and urine formation which otherwise would increase pelvic pressure. A resetting to a higher sensitivity was also elicited by intraarterial or intratubular administration of bradykinin. This suggests that thromboxane release may be mediated through an increased bradykinin production during volume expansion in hydronephrotics. In contrast, bradykinin resets TGF to a lower sensitivity in control kidneys.
Morsing
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P
Department of Physiology and Biophysics, University of Lund, Sweden.
Persson
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D000818:Animals; D001920:Bradykinin / Q000502:physiology; D005246:Feedback; D006869:Hydronephrosis / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000503:physiopathology*; D007684:Kidney Tubules / Q000503:physiopathology*; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D013931:Thromboxanes / Q000502:physiology; D014517:Ureteral Obstruction / Q000503:physiopathology*
D013931:Thromboxanes; D001920:Bradykinin