Effect of diuretics on the tubuloglomerular feedback response

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Abstract
To study the influence of diuretics on the tubuloglomerular feedback mechanism, early proximal stop-flow pressure (SFP) was measured during loop exposure to different drug concentrations. SFP was recorded continuously during arrested flow and at a perfusion rate of 50 nL/min. The perfusate consisted of isotonic saline, to which varying amounts of furosemide, bumetanide, piretanide, or hydrochlorothiazide were added to obtain final concentrations between 10−6 and 10−4 M. The loop diuretics furosemide, bumetanide, and piretanide showed inhibition: an inverse log–linear relation between the luminal concentration and the respective feedback response. No differences between the dose–response curves of furosemide, bumetanide, or piretanide could be demonstrated. The effective concentration range was between 10−6 and 10−4 M, the mean effective dose (ED50) was close to 10−5 M for each of them. In contrast, hydrochlorothiazide did not alter the feedback response. The effect of loop diuretics was rapidly and repeatedly reversible.

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