Summary
The influence of inhibitors of renal tubular reabsorption and/or of renal tubular secretion of uric acid on the urinary excretion of uric acid was studied in unanesthetized unloaded rats (plasma concentration of uric acid 1 to 1.5 mg-%), in animals preloaded by the intravenous route (plasma uric acid 1.5 to 5 mg-%) and in rats preloaded intraperitoneally and intravenously (plasma uric acid 5 to 15 mg-%).
Probenecid (200 mg/kg b.w.) had a pronounced uricosuric effect at the physiological low plasma level of uric acid. This effect became far less conspicuous at higher plasma levels. Sulfinpyrazone (50 mg/kg b.w.) had no significant uricosuric effect. Hydrochlorothiazide (priming 5 mg/kg b.w., infusion of 1 mg/min·kg b.w.) was equally ineffective.
The infusion of PAH (priming 25 mg/kg b.w., infusion of 3,5 mg/min·kg b.w.) or of pyrazinamide (priming 100 mg/kg b.w., followed by 1.2 mg/min·kg b.w.) depressed the tubular secretion of uric acid at high plasma levels. This effect was far less marked at medium or at low plasma levels.
The data are discussed.
Résumé
L'excrétion rénale de l'acide urique a été étudiée chez le rat nonanesthésié par des mesures de clearances, avant et après l'administration d'agents inhibiteurs des transports d'acide urique.
Le probénécide (200 mg/kg p.c., i.v.) a un effet uricosurique très significatif chez des animaux à taux plasmatique d'acide urique normal; cet effet diminue avec l'augmentation du taux plasmatique d'acid urique.
La sulfinpyrazone (50 mg/kg p.c., i.v.) n'a pas d'effet uricosurique significatif, quel que soit le taux plasmatique d'acide urique.
L'hydrochlorothiazide (5 mg/kg p.c., i.v., puis 1 mg/min·kg p.c., i.v.) n'a pas d'effet significatif sur l'excrétion rénale de l'acide urique chez le rat.
Le PAH (25 mg/kg p.c., i.v., puis 3,5 mg/min·kg p.c., i.v.) et la pyrazinamide (100 mg/kg p.c., i.v., puis 1,2 mg/min·kg p.c., i.v.), inhibiteurs de la sécrétion, diminuent d'autant plus fortement l'excrétion d'acide urique, que le taux plasmatique d'acide urique est plus élevé.
L'interprétation de ces observations est discutée.
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Les travaux ont bénéficié du soutien financier du Fonds National Suisse de la Recherche Scientifique (Crédits no. 4983′3 et 3′44′68).
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Boudry, J.F. Effet d'inhibiteurs des transports transtubulaires sur l'excrétion rénale d'acide urique chez le rat. Pflugers Arch. 328, 279–291 (1971). https://doi.org/10.1007/BF00586831
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DOI: https://doi.org/10.1007/BF00586831