Figure 6. A proposed schematic diagram depicting the synergistic diuretic effects of ACTZ and HCTZ in rats.

The combined inhibition of NCC and pendrin can cause significant salt and water wasting in the setting of increased delivery of salt from proximal tubule. Figure 6 (left panel): The carbonic anhydrase inhibitor Acetazolamide (ACTZ) increases the delivery of salt out of proximal tubule, down-regulates pendrin and activates NCC, which is depicted with thick yellow arrows; Fig. 6 (right panel): Combined ACTZ and HCTZ treatment in rats pretreated with ACTZ causes severe salt wasting due to the inhibition of NCC in the setting of pendrin downregulation and increased delivery of salt from the proximal tubule. The increased salt excretion in the latter group (Fig. 6b) is depicted with wide diameter light green columns in the collecting duct.