Summary
The influence of variation of perfusion flow rate on the renal clearance of p-aminohippuric acid and 1-naphthol was studied with an isolated perfused rat kidney preparation. Kidney functions were well maintained at low perfusion flow rates by the use of a fluorocarbon emulsion to increase the oxygen capacity of the perfusion buffer. Renal extraction of p-aminohippuric acid decreased with increasing perfusion flow. Our data show that at high perfusion flow rates maximal extractable perfusion flow forms only a small part of the total perfusion flow. 1-Naphthol is rapidly metabolized to its glucuronide and sulfate conjugate in the isolated perfused rat kidney. Using PAH as a marker for the maximal extractable perfusion flow, 1-naphthol could be regarded as a high-extraction compound even at high perfusion flow rates. Our results suggest that p-aminohippuric acid clearance, rather than total perfusion flow rate, should be used as the measure of maximal extractable blood flow for the estimation of extraction ratio in the isolated perfused kidney of compounds excreted or metabolized by the proximal tubules.
Similar content being viewed by others
References
Barger AC, Herd JA (1973) Renal vascular anatomy and distribution of blood flow. In: Orloff J, Berliner RW (eds) Handbook of physiology: renal physiology. American Physiological Society, Washington, DC, pp 249–313
Bekersky I (1983) Use of the isolated perfused kidney as a tool in drug disposition studies. Drug Metab Rev 14: 931–960
Bowman RH (1975) The perfused rat kidney. Methods Enzymol 39: 3–11
Cortney MA, Mylle M, Lassiter WE, Gottschalk CW (1965) Renal tubular transport of water, solute, and PAH in rats loaded with isotonic saline. Am J Physiol 209: 1199–1205
De Mello G, Maack T (1976) Nephron function of the isolated perfused rat kidney. Am J Physiol 231: 1699–1707
De Vries MH, Hofman GA, Koster AS, Noordhoek J (1989) Systemic intestinal metabolism of 1-naphthol. A study in the isolated vascularly perfused rat small intestine. Drug Metab Disp 17: 573–578
Dume T, Koch KM, Krause HH, Ochwadt B (1966) Kritischer venöser Sauerstoffdruck an der erythrocytenfrei perfundierten isolierten Rattenniere. Pflügers Arch 290: 89–100
Franke H, Weiss C (1976) The O2 supply of the isolated cell-free perfused rat kidney. In: Grote J, Reneau D, Thews G (eds) Oxygen transport to tissue. Plenum Press, New York London, pp 425–432
Gollan JH, Dallinger KJC, Billing, BH (1978) Excretion of conjugated bilirubin in the isolated perfused rat kidney. Clin Sci Mol Med 54: 381–389
Goodman MN, Parilla R, Toews CJ (1973) Influence of fluorocarbon emulsions on hepatic metabolism in perfused rat liver. Am J Physiol 225: 1384–1388
Hori R, Tanigawara Y, Saito Y, Hayashi Y, Aiba T, Okumura K, Kamiya A (1988) Moment analysis of drug disposition in kidney: transcellular transport kinetics of p-aminohippurate in the isolated perfused rat kidney. J Pharm Sci 77: 471–476
Lee L-J, Smith DE (1988) Renal excretion and metabolism of p-aminohippurate in the isolated perfused rat kidney. Pharm Res 5: 745–747
Lee L-J, Cook JA, Smith DE (1988) Renal transport kinetics of chlorothiazide in the isolated perfused rat kidney. J. Pharmacol Exp Ther 247: 203–208
Maack T (1980) Physiological evaluation of the isolated perfused rat kidney. Am J Physiol 238: F71-F78
Maack T (1986) Renal clearance and isolated kidney perfusion techniques. Kidney Int 30: 142–151
Nissen OI (1968) The extraction fraction of p-aminohippurate in the superficial and deep venous drainage areas of the cat kidney. Acta Physiol Scand 73: 329–338
Redegeld FA, Hofman GA, Noordhoek J (1988) Conjugative clearance of 1-naphthol and disposition of its glucuronide and sulfate conjugates in the isolated perfused rat kidney. J Pharmacol Exp Ther 244: 263–267
Ross BD (1978) The isolated perfused rat kidney. Clin Sci Mol Med 55: 513–521
Schurek HJ, Brecht JP, Lohfert H, Kierholzer K (1975) The basic requirements for the function of the isolated cell free perfused rat kidney. Pflügers Arch 354: 349–365
Schuster VL, Seldin DW (1985) Renal clearance. In: Seldin DW, Giebisch G (eds) The kidney. Physiology and pathophysiology. Raven Press, New York, pp 365–395
Steele TH, Stromberg BA, Underwood JL (1982) Inhibitory action of urate on p-aminohippurate secretion by the isolated rat kidney. Nephron 31: 266–269
Stein JH, Boonjarern S, Wilson CB, Ferris TF (1973) Alterations in intrarenal blood flow distribution. Methods of measurement and relationship to sodium balance. Circ Res [Suppl. 1] 3233: 61–71
Szefler SJ, Acara M (1979) Isoproterenol excretion and metabolism in the isolated perfused rat kidney. J Pharmacol Exp Ther 210: 295–300
Tremaine LM, Diamond GL, Quebbemann AJ (1984) In vivo quantification of renal glucuronide and sulfate conjugation of 1-naphthol and p-nitrophenol in the rat. Biochem Pharmacol 33: 419–427
Tremaine LM, Diamond GL, Quebbemann AJ (1985) Quantitative determination of organ contribution to excretory metabolism. J Pharmacol Methods 13: 9–35
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Redegeld, F.A.M., Hofman, G.A., Koster, A.S. et al. Flow-dependent extraction of 1-naphthol by the rat isolated perfused kidney. Naunyn-Schmiedeberg's Arch Pharmacol 343, 330–333 (1991). https://doi.org/10.1007/BF00251135
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00251135