Abstract
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.
Footnotes
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Send reprint requests to: Dr. S. J. Walter, Division of Biomedical Sciences, Imperial College School of Medicine, Charing Cross Hospital, Fulham Palace Rd., London W6 8RF, UK.
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↵1 Supported by a Livingston Scholarship.
- Abbreviations:
- ATP
- adenosine triphosphate
- GFR
- glomerular filtration rate
- MABP
- mean arterial blood pressure
- PCV
- packed cell volume
- PNa
- PK, PIn, plasma concentration of sodium, potassium and inulin, respectively
- SNGFR
- single nephron glomerular filtration rate
- TAL
- thick ascending limb of Henle
- TFNa
- TFK, TFIN, tubular fluid concentration of sodium, potassium and inulin, respectively
- Uosm
- urine osmolality
- V
- UNaV, UKV, excretion rates of fluid, sodium and potassium, respectively
- VTF
- tubular fluid flow rate
- Received August 25, 1997.
- Accepted January 12, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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