Isolated perfused rat kidney

FIGURE 9.14 Effects of adenosine receptor agonist 2-chloro-adenosine on vascular perfusion pressure of isolated perfused rat kidneys. Minor effects seen in untreated kidneys (filled circles) and pronounced vasoconstriction while vasodilatation in kidneys coperfused with subthreshold concentrations of a-adrenoceptor vasoconstrictor methoxamine and vasodilatatory activation of adenylyl cyclase with forskolin (open circles). Redrawn from [49]. 

Sawai, K., Mahato, R.I., Oka, Y., Takakura, Y. and Hashida, M. (1996) Disposition of oligonucleotides in isolated perfused rat kidney involvement of scavenger receptors in their renal uptake. J. Pharmacol. Exp. Then, 279, 284-290. 

R4. Raz, E., Brezis, M., Rosenmann, E., and Eilat, D., Anti-DNA antibodies bind directly to renal antigens and induce kidney dysfunction in the isolated perfused rat kidney. J. Immunol. 142, 3076-3082 (1989). 

A comprehensive reivew of studies of the action of DA, agonists and antagonists in isolated blood vessels and organs was recently published (31). In general, there is good correlation between in vivo and in vitro data with isolated canine blood vessels. However, exceptions have been reported with isolated preparations of other species. The major differences are that sulpiride and its enantiomers appear to be much more potent in vivo than in vitro. Another discrepancy is that bromocriptine, which is inactive on DA, receptors in vivo, has been shown to cause DA-like vasodilation of the isolated perfused rat kidney and relaxation of rabbit mesenteric artery strips. 

Hori R, Okamura N, Aiba T, et al. Role of P-glycoprotein in renal tubular secretion of digoxin in the isolated perfused rat kidney. J Pharmacol Exp Ther 1993 266 1620-1625. 

Because of the kidney s involvement in the excretion of hydrophilic compounds and because most of the substrates of P-gp are hydrophobic compounds that are likely to be cleared mainly by biliary excretion or intestinal secretion, comparably fewer studies have been performed with the isolated perfused kidney. The isolated perfused rat kidney model was used to demonstrate that digoxin is actively secreted by P-gp located on the luminal membrane of renal tubular epithelial cells and that clinically important interactions with qui-nidine and verapamil are caused by the inhibition of P-gp activity in the kidney (332). These results provide an excellent example of how the isolated perfused kidney model can be used to definitively conclude that P-gp-mediated efflux is involved in the renal excretion of a compound and also to elucidate possible DDIs that might arise in the kidney following coadministration of P-gp sub strates/inhibitors. 

Verbeuren TJ. Vasodilator effect of tertatolol in isolated perfused rat kidneys involvement of endothelial 5-HT1A receptors. Cardiology 1993 83(Suppl 1) 5—9. 

Verbeuren TJ, Mennecier P, Laubie M. 5-Hydroxytryptamine-induced vasodilatation in the isolated perfused rat kidney are endothelial 5-HT1A receptors involved Eur J Pharmacol 1991 201 17-27. 

Tarako et al. (1991) evaluated oxygen supply and energy state in the isolated perfused rat kidney. Metabolic activities of the isolated perfused rat kidney were described by Nishiitsutsuji-Uwo et al. (1967). Cox et al. (1990) used the isolated perfused rat kidney as a tool in the investigation of renal handling and effects of nonsteroidal anti-inflammatory drugs. 

Maack T (1980) Physiological evaluation of the isolated perfused rat kidney. Am J Physiol 238 F71-F78 Newton JF, Hook JB (1981) Isolated perfused rat kidney. Meth Enzymol 77 94-105... 

Nishiitsutsuji-Uwo JM, Ross BD, Krebs HA (1967) Metabolic activities of the isolated perfused rat kidney. Biochem J 103 852-862... 

Isolated perfused rat kidneys are used for physiological and pharmacological purposes to study overall renal functions. For pharmacokinetic purposes this preparation is used to study renal excretion profiles of the candidate compound and/or its metabolites. 

In man, the volume of distribution of the cyclic nucleotides exceeds the extracellular fluid space [125], and only about 15% of injected labelled cyclic AMP is excreted by the kidney. Extrarenal cyclic nucleotide clearance probably involves hepatic metabolism and/or biliary excretion, but cyclic AMP is also destroyed by renal phosphodiesterase. The isolated perfused rat kidney rapidly removes cyclic AMP from the perfusion medium [126]. 

Willinger, C.C. Schramek, H. Pfaller, K. Joannidis, M. Deetjen, P. Pfaller, W. Ultrapure polymerized bovine hemoglobin improves structural and functional integrity of the isolated perfused rat kidney. Renal Physiol. Bio-chem. 1995,18, 288-305. 

Van Crugten JT, Sallustio BC, Nation RL, Somogyi A. Renal tubular transport of morphine, morphine-6-glucuronide, and mor-phine-3-glucuronide in the isolated perfused rat kidney. Drug Metab Disp 1991 19 1087-1092. 

Koschier FJ, Acara M.Transport of 2,4,5-trichlorophenoxyacetate in the isolated, perfused rat kidney. J Pharmacol ExpTher 1979 ... 

Bekersky I, Colburn WA. Acetylation of sulfisoxazole by the isolated perfused rat kidney. J Pharm Sci 1980 69 1359. 

Brezis M, Rosen S, Silva P, and Epstein ELI. Selective vulnerability of the medullary thick ascending limb to anoxia in the isolated perfused rat kidney.The Journal of Clinical Investigation 73 182-190,1984. 

A huge number of studies of experimental renal injury have been performed using the isolated perfused rat kidney. Studies have explored vascular and tubular responses to toxic and hypoxic injury and to mediators thought to participate in regulation of normal renal function as well as in the biochemical and morphological changes accompanying renal injury. 

Three main models have been used. The intact isolated perfused rat kidney (IPRK), is the most widely used model and first developed for the study autoregulation by Weiss et al in [262]. However, this prototype was little used initially because autoregulation and function declined after only 15-30 minutes. However, when simpler surgery and improved perfusion solutions were introduced by Ross, the model became useful for studies of renal biochemistry [263, 264]. With further improvements, including the addition of amino acids [265,266] and sometimes erythrocytes [267-269] the model became useful for studies of physiology and... 

Eoutzenhiser R, Flayashi K, Epstein M Atrial natriuretic peptide reverses afferent arteriolar vasoconstriction and potentiates efferent arteriolar vasoconstriction in the isolated perfused rat kidney. J.PharmacoI.Exp.Ther. 246 522-528,1988... 

Schurek FIJ, Kriz W Morphologic and functional evidence for oxygen deficiency in the isolated perfused rat kidney. Lab Invest 53 145-155,1985... 

Lieberthal W, Stephens GW, Wolf EF, Rennke FIG, Vasilevsky ML, Valeri CR, Levinsky NG Effect of erythrocytes on the function and morphology of the isolated perfused rat kidney. Ren Physiol 10 14-24,1987... 

Ratcliffe PJ, Endre ZFI, Scheinman SJ, Tange JD, Ledingham JG, Radda GK 31P nuclear magnetic resonance study of steady-state adenosine 5 -triphosphate levels during graded hypoxia in the isolated perfused rat kidney. Clin.Sci. 74 437-448,1988... 

Loutzenhiser R, Epstein M, Elorton C Inhibition by diltiazem of pressure-induced afferent vasoconstriction in the isolated perfused rat kidney. Am J Cardiol 59 72-75,1987... 

Dowd T, Barac-Nieto M, Gupta RK, Spitzer A 31P nuclear magnetic resonance and saturation transfer studies of the isolated perfused rat kidney. Ren Physiol Biochem 12 161 -70,1989... 

Cowin GJ, Leditschke lA, Crozier S, Brereton IM, Endre ZH Regional proton nuclear magnetic resonance spectroscopy differentiates cortex and medulla in the isolated perfused rat kidney. MAGMA 5 151-8,1997... 

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