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Vol. 285, Issue 2, 464-467, May 1998
Division of Biomedical Sciences, Imperial College School of
Medicine, London, United Kingdom
The renal effects of glibenclamide were investigated using free flow
micropuncture techniques in anesthetized Sprague-Dawley rats.
Intravenous infusion of the drug (3 mg/hr) evoked a natriuresis and
diuresis; potassium excretion remained unchanged. Fractional reabsorption in the proximal convoluted tubule in glibenclamide-infused rats did not differ significantly from that in control animals, although the late proximal tubular fluid to plasma concentration ratio
for potassium was reduced. Fractional sodium delivery to the early
distal tubule was elevated, while the fractional deliveries of water
and potassium to this nephron site were unaffected. We conclude that
glibenclamide impairs sodium reabsorption in one or more of the nephron
segments that comprise the loop of Henle. These results are consistent
with the hypothesis that the natriuresis resulting from glibenclamide
administration is a consequence of blockade of potassium channels in
the apical membrane of the thick ascending limb of Henle's loop. The
data suggest that glibenclamide may additionally inhibit a small
secretory potassium flux in the proximal tubule.
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