Localization of diuretic effects along the loop of Henle: an in vivo microperfusion study in rats

In order to clarify the effects on sodium reabsorption in the loop of Henle of methazolamide (a carbonic anhydrase inhibitor), chlorothiazide and the loop diuretics frusemide and bumetanide. superficial loops were perfused in vivo in anaesthetized rats and the individual diuretics were included in t he perfusate. Differentiation between effects in the pars recta and in the thick ascending limb of Henle (TALH) was achieved by comparing responses to the diuretics when using a standard perfusate, designed to mimic native la te proximal tubular fluid, and a low-sodium perfusate, designed to block ne t sodium reabsorption in the pars recta. With the standard perfusate, metha zolamide caused decreases in sodium reabsorption (J(Na)) and water reabsorp tion (J(V)); with the low-sodium perfusate, a modest effect on J(Na) persis ted, suggesting that carbonic anhydrase inhibition reduces sodium reabsorpt ion in both the pars recta and the TALH. The effects of chlorothiazide were very similar to those of methazolamide with both the standard and low-sodi um perfusates, suggesting that chlorothiazide also inhibits sodium reabsorp tion in the pars recta and TALH, perhaps through inhibition of carbonic anh ydrase. With the standard perfusate, both frusemide and bumetanide produced the expected large decreases in J(Na), but J(V) was also lowered. With the low-sodium perfusate, the inhibitory effects of the loop diuretics, partic ularly those of frusemide, were substantially reduced, while net potassium secretion was found. These observations indicate that a significant compone nt of the effect of frusemide (and possibly of bumetanide) on overall sodiu m reabsorption is located in the pars recta, and that loop diuretics induce potassium secretion in the TALH.