Effect of diuretics on the tubuloglomerular feedback response

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.