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OtherRENAL PHARMACOLOGY

Renal Effects of Glibenclamide: A Micropuncture Study

M. A. Bailey and S. J. Walter
Journal of Pharmacology and Experimental Therapeutics May 1998, 285 (2) 464-467;
M. A. Bailey
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S. J. Walter
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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

  • 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.

  • ↵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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Journal of Pharmacology and Experimental Therapeutics
Vol. 285, Issue 2
1 May 1998
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Renal Effects of Glibenclamide: A Micropuncture Study

M. A. Bailey and S. J. Walter
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 464-467;

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OtherRENAL PHARMACOLOGY

Renal Effects of Glibenclamide: A Micropuncture Study

M. A. Bailey and S. J. Walter
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 464-467;
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