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Phenylbutazone-induced decrease in renal blood flow.

H E Williamson, G R Gaffney, W A Bourland

    The Journal of Pharmacology and Experimental Therapeutics
    |January 1, 1978
    PubMed
    Summary
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    Phenylbutazone, an anti-inflammatory drug, reduces renal blood flow and sodium/water excretion in dogs. This suggests a hemodynamic mechanism, potentially involving prostaglandins, underlies its effects on kidney function.

    Area of Science:

    • Nephrology
    • Pharmacology
    • Renal Physiology

    Background:

    • Phenylbutazone (Butazolidin) is an anti-inflammatory agent known to decrease renal excretion of sodium and water.
    • The underlying mechanism for this effect, particularly concerning renal hemodynamics, requires further investigation.

    Purpose of the Study:

    • To investigate whether alterations in renal hemodynamics are involved in the sodium and water retention caused by phenylbutazone.
    • To explore the potential role of prostaglandins in phenylbutazone's renal effects.

    Main Methods:

    • Anesthetized dogs were used to monitor renal blood flow (RBF) using electromagnetic flow probes.
    • Phenylbutazone was administered intravenously at a dose of 2 mg/kg.
    • Renal function parameters, including glomerular filtration rate (GFR), sodium, and water excretion, were measured.

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    Main Results:

    • Intravenous phenylbutazone administration led to a 20% decrease in RBF, reduced GFR, and decreased sodium and water excretion.
    • A slight increase in blood pressure was observed.
    • The reduction in RBF correlated with decreased renal prostaglandin E secretion.
    • Pretreatment with indomethacin (a prostaglandin synthesis inhibitor) abolished phenylbutazone's effects on renal hemodynamics and excretion.
    • Phenylbutazone inhibited furosemide-induced increases in RBF, similar to indomethacin's known effect.

    Conclusions:

    • Phenylbutazone's effects on renal hemodynamics, including reduced RBF and GFR, suggest a hemodynamic mechanism contributes to sodium and water retention.
    • Prostaglandin E may play a role in mediating these renal effects.
    • Phenylbutazone's actions on renal mechanisms resemble those of indomethacin, indicating a shared pathway involving prostaglandin inhibition.