Evidence has been presented in the past that
muzolimine might act at a localization differently to sulfamoyl-type
diuretics and/or with a different or additional mechanism. This is further supported by the fact that at the maximum of the dose-response curves for
muzolimine and
furosemide in rats, a combination of maximal oral doses still results in significantly higher
sodium excretion. To further substantiate that this aspect of
muzolimine is of relevance, e. g. for the
therapy of
acute renal failure,
muzolimine treatment by food or implanted osmotic minipumps was employed in an obstructive model of severe renal
ischemia in rats. Acute renal
ischemia was induced in Wistar rats by clamping the left renal pedicle for 60 minutes with a microsurgery clamp. The right kidney had been removed four days before
ischemia. Clearance data were obtained on the first, third and on the ninth to fourteenth days after
ischemia in the surviving animals. Renal
ischemia resulted in
anuria, increased mortality and impaired renal function with histopathologically apparent tubular obstruction in the untreated controls. Treatment with
muzolimine by food (in a concentration of 800 ppm for four days) and additional oral gavage one hour prior to
ischemia prevented the sequelae of
ischemia to a great extent. Similar beneficial effects could be obtained by therapeutic implantation of osmotic minipumps ensuring administration of 0.44 micrograms
muzolimine/h per animal. These results in rats further support the suggestion that
muzolimine might act differently to sulfamoyl-
diuretics. Furthermore, they strongly implicate
muzolimine as the
diuretic of choice in
acute renal failure.