circulation research 1975 finn 675 81

Circulation Research JUNE 1975

VOL. 36 NO. 6

An Official Journal of the American Heart Association

Brief Reviews

Pathogenesis of Oliguria in Acute Renal Failure

By William F. Finn, William J. Arendshorst, and Carl W. Gottschalk

• Nearly half a century has passed since Dr. A. N.Richards described his findings of continued glo-merular filtration in a frog made anuric with HgCl2

(1). Although his concept that nearly all of theglomerular filtrate passively moves across damagedtubular epithelial cells was given support by themicrodissection studies of Dr. Jean Oliver et al. (2),the intervening years have not seen a consensus asto the factors responsible for the oliguria of acuterenal failure.

Despite the facts that several pathophysiologicalevents relating to the presence of oliguria have beenidentified and that each has received experimentalsupport (3), a persisting controversy exists concern-ing the relative importance of tubular obstruction,passive backflow of filtrate, and failure of filtrationdue to such causes as preglomerular vasoconstric-tion, a decrease in glomerular plasma flow, or analteration in the ultrafiltration coefficient of theglomerular capillary membranes. The situationbecomes particularly complex in those experimen-tal models in which more than one abnormality isfound. Nonetheless, data accumulated over thepast decade have led some to conclude that "...aprimary abnormality in glomerular filtration playsa major role in all models to date, presumablyreflecting significantly increased preglomerularvascular resistance" (4). As a result, it has beensuggested that the syndrome of oliguric acute renalfailure is most accurately referred to as "vasomotornephropathy" (5). We believe, however, that theinitial insult, whether it be due to ischemia,nephrotoxins, or a combination of both, sets intomotion a series of events which are self-perpetuat-ing. Such a sequence is illustrated in Figure 1. Inthis frame, one factor or another may assumepredominance at any given time and obscure thecontribution of others. Thus, we feel that it is

From the Departments of Medicine and Physiology, Univer-sity of North Carolina School of Medicine, Chapel Hill, NorthCarolina 27514.

Circulation Research, Vol. 36, June 1975

advisable not to ascribe the oliguria to a singlecause but rather to discuss it in terms of itsgeneration and maintenance.

The development of this perspective has beenaided by the application of an electronic servo-null-ing pressure apparatus (6, 7) and by the identifica-tion by Dr. Klaus Thurau of a strain of Munich-Wistar rats possessing glomeruli on the surface ofthe kidney. This anatomy permits the direct mea-surement of glomerular capillary hydrostatic pres-sure and the assessment of changes in pre- andpostglomerular vascular resistances. Use of thepressure apparatus also allows continuous monitor-ing of intratubular pressure during microinjectionexperiments to determine tubular permeabilitycharacteristics—a necessity when potentially dis-eased or damaged nephrons are considered. Inaddition, the recent availability of a noncannulat-ing electromagnetic flow transducer of smallenough size to measure blood flow in the rat kidneywithout interfering with normal kidney functionallows for the first time accurate and instantaneousmeasurements of renal blood flow during a series ofexperimental observations (8). This method ap-pears to be the one of choice for determining renalblood flow in the diseased kidney when the validityof other techniques such as the para-aminohippuricacid clearance-extraction method may be suspect.

It is the purpose of this review to examinecritically some of the micropuncture data whichare supportive of each of the proposed pathophysio-logical mechanisms of oliguric acute renal failure.Included will be information recently obtained inour laboratory and a summary of what we believeto be a unifying hypothesis concerning the eventsresponsible for the generation and the maintenanceof the oliguria.

FILTRATION FAILURE

The most compelling data implicating altera-tions in preglomerular vascular resistance as the

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6 7 6 FINN. ARENDSHORST, GOTTSCHALK

FIGURE 1

Schema of interrelated events which may follow acute circula-tory or toxic renal damage. Alterations in glomerular capillarypressure, permeability, and blood flow lead directly to areduction in filtration and urine formation; obstruction of thetubules retards the flow of filtrate and promotes backleakageacross damaged epithelium. The factors are not mutuallyexclusive nor are all necessarily present; moreover, they proba-bly vary in importance between different models and from timeto time in the same model. For details, see text.

major physiological abnormality in the reduction offiltration and the subsequent development of oli-guria come from the studies of mercury- andglycerol-induced acute renal failure in rats by Okenand his colleagues. In their initial studies, Flaniganand Oken (9) employed relatively large doses ofHgCl2 (12 mg/kg, im). Periodically over the next24 hours, they observed the appearance of thekidney in vivo, measured proximal intratubularpressures, and estimated intratubular flow rates.For the first 6 hours after mercury injection, thesurface of the kidney appeared normal; then, thelumens of some tubules became narrow and thecells granular. By 24 hours, virtually all of thetubules were pale and coarsely granular and hadextremely narrow or no lumens; there appeared tobe little or no tubular flow. At no time, however,was any disturbance in peritubular capillary flowobserved. Proximal intratubular pressure was nor-mal the first 4-8 hours but decreased thereafterwith a greater than normal variability betweennephrons. At 6 hours, single nephron glomerularfiltration rate and absolute water reabsorptionwere diminished. These authors were not able toquantify water movement after 6 hours, but theyarrived at qualitative estimates of intratubularflow rates by observing the behavior of smalldroplets injected into the tubules. The percent ofnephrons with normal flow decreased progressivelyso that flow was minimal or absent at 24 hours.

These authors concluded that, since glomerularfiltration rate fell without an increase in intratubu-

lar pressure, tubular obstruction per se was not theresponsible factor. Furthermore, they felt that thetubular obstruction by debris which was present inlater phases resulted from the aggregation of parti-cles when tubular flow was reduced and was not thecause of the diminished tubular flow. Since noexperiments were done on rats whose mean arterialblood pressure was less than 85 mm Hg, theauthors postulated that a primary decrease inglomerular filtration rate such as that which couldbe produced by preglomerular vascular constric-tion, postglomerular dilatation, or both, was theinitial cause of anuria. Their results, which in-cluded the observation that reabsorption of salinedroplets between oil columns decreased progres-sively with time and was almost nonexistent at 24hours, led them to discount the possibility thatanuria resulted from continuing filtration withtotal reabsorption of the filtrate through passivebackflow.

Oken and his colleagues next turned to glycerol-induced acute renal failure in rats (10). Theyinvestigated this model extensively, since theybelieved that it was more closely related to thesyndrome of acute renal failure in man, althoughthe complexity of the model greatly complicates anunderstanding of its pathogenesis. Marked swellingof the injected muscles , destruction of muscle cellsand red blood cells, and excretion of myoglobin andhemoglobin all occur. Undoubtedly, there are alter-ations in body fluid compartments, probably in-volving circulating blood volume; renal vasocon-striction even with normal blood pressure seems tobe an a priori expectation. The sequence of eventsfound by Oken and his associates was very similarto that described in the high-dose mercury poison-ing experiments just discussed with the addition ofan acute but transitory change in renal blood flow.Qualitative estimates of proximal flow rates ob-tained by observing the behavior of a small oildroplet injected into a nephron showed decreasingflow over a 24-hour period, especially in dehydratedrats. Single nephron glomerular filtration rate andabsolute water reabsorption were diminished. Atno time was there evidence of increased intratubu-lar pressure; proximal intratubular pressure wasreduced both early and later in the development ofthe syndrome even though pigment casts appearedin the tubules.

Again these authors came to similar conclusions,namely that a decreased rate of filtration andproximal flow resulted from failure of filtration dueto vascular changes and that tubular obstructionand increased leakiness of the tubule were not




ACUTE RENAL FAILURE 677

causes of the oliguria. They felt that their findingscould be most logically attributed to an aberrationin afferent-efferent arteriolar tone.

Inasmuch as neither renal blood flow nor glomer-ular capillary hydrostatic pressure was measured,an alternate explanation of this interpretation ispossible. Cox et al. (11) have recently suggestedthat alterations in the ultrafiltration coefficient(Kr) of the glomerular capillary membrane resultin oliguria in the presence of normal renal vascularresistance. In their experiments, acute renal failurewas produced by a temporary infusion of norepi-nephrine. Renal blood flow returned to normalfollowing the administration of 10% of the bodyweight of Ringer's solution, but lissamine green,injected intravenously, was not seen to pass intoproximal tubules which remained collapsed. Ex-amination of glomeruli by scanning electron mi-croscopy showed distortion of the normal architec-ture with crowding of the primary, secondary, andfoot processes of podocytes. Whether decreases inglomerular capillary permeability lower filtrationrate in other models of acute renal failure is notknown.' It is possible that the opposite could occur.

Brenner's laboratory has reported that the Kf ofMunich-Wistar rats is higher than had been previ-ously predicted from indirect studies in the dog andthe rat (12). Furthermore, their studies indicatethat, because filtration pressure equilibrium isnormally achieved along the glomerular capillary,glomerular filtration rate is related to glomerularplasma flow (13). In studies following 3 hoursof incomplete renal ischemia, they attributed theensuing decrease in filtration to a marked reduc-tion of glomerular plasma flow (14). Although therats were not oliguric, their data are not inconsist-ent with the concept that preglomerular vasocon-striction bears the primary responsibility for theobserved changes.

It should be mentioned, however, that in themodels under consideration the finding of normalintratubular pressures does not by itself eliminatethe possibility of significant tubular obstruction. Areduction in glomerular capillary hydrostatic pres-sure could mask the degree of intratubular obstruc-tion by reducing the effective filtration pressure. Inaddition, marked changes in the permeability andthe integrity of the tubular epithelium could favorthe passive backflow of tubular fluicl and limit thedevelopment or the maintenance of a transmural

1 It has very recently been suggested that glomerular permea-bility in rats given uranyl nitrate is significantly reduced beforethe onset of definite electron micrographic changes in theglomerulus (Blantz RC: Mechanism of acute renal failure afteruranyl nitrate. J Clin Invest 55:621-635, 1975).


pressure gradient, again obscuring the presence ofintratubular obstruction.

PASSIVE BACKFLOW OF GLOMERULAR FILTRATE

The principal contemporary work that appearsto support the passive backflow mechanism is the1967 study by Bank and his colleagues (15). Ratsinjected with a low dose of mercuric chloridebecame anuric in about 24 hours following anearlier diuretic phase. The rats remained anuric foranother 24 hours after which time urine outputreturned. The most striking data are color photo-micrographs of the surface of a normal and amercury-treated rat kidney following intravenousinjection of lissamine green. The dye rapidly ap-peared in the peritubular capillaries of both kid-neys, and the usual progression down the proximaltubule was seen in the normal kidney. In themercury-treated rat kidney, in contrast, the colorof the dye became progressively lighter as it flowedthrough coils of proximal convolutions and wasbarely visible in the terminal segments of theproximal tubule. It never appeared in distal con-volutions. These observations suggested to theauthors that the proximal epithelium had becomeabnormally permeable to lissamine green. Singlenephron glomerular filtration rate determined fromtubular fluid collected at various sites along thenephron appeared to support this point of view.Single nephron glomerular filtration rate was nor-mal when it was determined on fluid collected fromthe early proximal tubule but was only 37% of thisvalue when it was determined on fluid collectedfrom the late proximal tubule and 26% of normalwhen it was determined on fluid collected fromdistal convolutions. The authors felt that theseobservations supported their supposition of exten-sive passive backflow or leakage of tubular fluid.

Several questions can be raised about this inter-pretation, however. The most extensive morpholog-ical changes following the administration of lowdoses of mercury like those used in these experi-ments, and in fact the only changes visible by lightmicroscopy, are in the pars recta of the proximaltubule (16). Yet the observations of Bank et al. (15)suggest extensive permeability changes in the parsconvoluta with little apparent inulin loss in thepars recta. It is possible that the apparent decreasein inulin flow along the tubule resulted from theselection of nephrons with heterogeneous singlenephron glomerular filtration rates and does nottruly represent transtubular inulin leakage. Inulinmicroinjections with very careful and continuousmeasurement of the intratubular pressure duringthe microinjection constitute a better method of



678 FINN, ARENDSHORST, GOTTSCHALK

determining inulin leakage. Another apparentanomaly of the experiments of Bank et al. (15) isthe fact that lissamine green did not appear indistal convolutions although fluid could be col-lected from them for inulin determinations. Thisobservation is similar to that reported several yearslater by Steinhausen and his colleagues (17). Theyalso followed lissamine green tubular flow in ratspoisoned with mercury and observed that the dyebecame progressively paler the further along theproximal tubule it flowed. However, Steinhausenand his colleagues concluded that this effect wasdue at least in part to protein-binding of lissaminegreen, since suffusion of the renal surface withdilute acid caused the reappearance of the lissa-mine green. To study further the possibility ofpassive backflow, Steinhausen et al. microinjectedinulin into proximal convolutions of rats treatedwith mercuric chloride. In one experiment all of theinulin was excreted in the urine from the ipsilateralkidney, indicating that there was no inulin leakage,but in the other five experiments there was verysignificant inulin excretion by the contralateralkidney. Rather surprisingly, however, in four of thefive experiments, inulin excretion by the contralat-eral kidney vastly exceeded excretion by the kidneycontaining the microperfused tubule. This findingis hard to understand, since inulin lost from atubule and absorbed into the peritubular capillaryblood should be excreted in equal amounts by bothkidneys unless there is preferential unilateral dam-age to one or the other of the kidneys. In any eventthere was apparently no control of hydrostaticpressure during the microperfusions, and clearly anincrease in intratubular pressure could have in-creased inulin leakage across an abnormallypermeable membrane. As a result, these experi-ments should not be considered conclusive.

The question at issue is not whether there is achange in renal tubular permeability. Clearly,there must be major changes when there is necrosisof the tubular epithelium; this fact can be easilydemonstrated. The question is the significance of apermeability change as a cause of anuria. Are therecircumstances under which, in the presence oftubular necrosis, filtration continues and the bal-ance of the driving forces—the physical factors—favors reabsorption? Tubular obstruction wouldtilt this balance of physical factors in that direc-tion, and we believe it is likely that some passivebackflow occurs under these conditions.

INTRATUBULAR OBSTRUCTION

Data suggesting a prominent role for tubularobstruction have been derived from micropuncture

studies performed following temporary completerenal artery occlusion in the rat (18, 19). It is worthnoting that many of the agents used to produceexperimental acute renal failure do so not only by adirect nephrotoxic effect but also in associationwith an ischemic period of variable extent andduration. For this reason it is somewhat surprisingthat acute renal failure produced by ischemia hasnot received wider attention by those engaged inrenal micropuncture studies. One complicatingfeature has been the reports by some that in the ratintrarenal circulation is not reestablished followingvariable periods of complete ischemia (20, 21). Thisso-called "no-reflow phenomenon" has been attrib-uted to a markedly increased renal vascular resist-ance due to endothelial cell swelling (22). In thisscheme, active sodium transport is inhibited dur-ing the period of ischemia, and intracellular so-dium and water accumulate with swelling of thecells and a reduction in the diameter of thevascular lumens. Hypertonic solutions have beenreported to decrease cell swelling through an os-motic effect and thus to reduce renal vascularresistance (22). This concept has received consider-able discussion and has been applied in the studyof the effects of ischemia on other vascular beds.For reasons to be mentioned later, we do notconsider this phenomenon to be a major componentof either the generation or the maintenance ofoliguria.

Those who did find some degree of reflow wereimpressed by their inability to measure accuratelyeither renal blood flow or glomerular filtration rateby the standard clearance methodology (23). Thisfailure was attributed to the leakage of tubularfluid across damaged epithelial cells, a point ofsome importance in considering the events leadingto oliguria. Data from several laboratories includ-ing our own (18, 19, 24) indicate that reflowgenerally occurs following 1 hour of temporaryrenal artery occlusion in the heparinized rat. Wefound that on release of the renal artery clamprenal blood flow measured by an electromagneticflow transducer rapidly returned to approximately50% of the control value. As blood flow returned,the previously collapsed tubules opened and thenbecame distended. The return of glomerular filtra-tion was confirmed by the appearance in the renalcirculation and the proximal tubules of FD & Cgreen injected intravenously. Dye remained inproximal tubules and was seen only rarely in distalconvolutions, suggesting the presence of tubularobstruction. Obstruction was confirmed by thepresence of markedly elevated proximal intratubu-lar pressure. Glomerular capillary hydrostatic pres-





sure at this time was normal whether it wasmeasured directly in Munich-Wistar rats or esti-mated from the sum of the intratubular stop-flowpressure and the arterial colloid osmotic pressure.Although renal vascular resistance was increasedas reflected by a decrease in renal blood flow at anunchanged perfusion pressure the resistancechanges were such as to maintain glomerularcapillary hydrostatic pressure. Tubular obstructionwas thus responsible for the generation of theoliguria.

Other rats were studied 24 hours after theischemic episode. Both proximal intratubular pres-sure and glomerular capillary hydrostatic pressurewere now significantly reduced, indicating thesecondary development of predominant pre-glomerular vasoconstriction. Although the decreasein proximal intratubular pressure did not suggestthe continued presence of intratubular obstruction,there were several observations which did. Promi-nent among these was the presence of intratubularcasts in histological sections. In addition, distalintratubular pressure remained elevated. As men-tioned earlier, one would expect proximal in-tratubular pressure to be reduced even in thepresence of obstruction when glomerular capillaryhydrostatic pressure is low and damaged andnecrotic tubular epithelium prevents the mainte-nance of large transtubular pressure gradients. Thelack of tubular integrity was made apparent by themicroinjection of dye at such a rate so as not toelevate the simultaneously recorded intratubularpressure. The dye was seen to form a "halo" aroundthe injected tubule as it entered the peritubularcirculation.

Under these circumstances, the relative impor-tance of augmented preglomerular vascular resist-ance in the maintenance of the oliguric state wasnot clear. Therefore, several maneuvers were madein an attempt to decrease renal vascular resistanceand restore glomerular capillary hydrostatic pres-sure toward normal. Neither the infusion of apotent competitive antagonist of angiotensin II(l-Sar-8-Ala-angiotensin II) nor the administrationof an alpha-adrenergic blocking agent (phenoxy-benzamine) significantly altered renal blood flowor renal vascular resistance. When rats were vol-ume expanded with isotonic saline or isoncotic ratplasma, however, renal blood flow promptly re-turned to normal values. This return was notassociated with any increase in urine flow. Bothglomerular capillary hydrostatic pressure and prox-imal intratubular pressure rose in response tovolume expansion, the latter to levels significantlyabove the control value. This observation clearlyCirculation Research, Vol. 36, June 1975

indicates the presence of continued tubular ob-struction as the predominant factor in the mainte-nance of oliguria. With regard to the relationshipbetween cell swelling and oliguria, data exist whichindicate that tubular epithelial cell swelling disap-pears promptly after the circulation is restored(25). Restoration of renal vascular resistance tonormal values by volume expansion with isosmoticfluid does not support the cell swelling theory.

It should be pointed out that if conclusions wereto be drawn from our pressure data alone it wouldappear that preglomerular vasoconstriction was themajor factor in the maintenance of the oliguria.When the pressure data are considered in relationto the events occurring in the early postischemicphase along with the morphological evidence andthe response to acute volume expansion, it is clearthat intratubular obstruction is a major factor inboth the generation and the maintenance of theoliguria in ischemia-induced acute renal failure.

The reasons for the development of increasedrenal vascular resistance are not known but may berelated to the presence of a vasoconstrictor, theabsence of a vasodilator, or a combination of both.Prostaglandin concentrations are known to in-crease in renal venous blood following temporaryrenal ischemia (26). Angiotensin itself stimulatesthe release of prostaglandins which tend to limitthe vasoconstrictor response of the renal vascula-ture (27). Administration of angiotensin in theabsence of prostaglandins, as with pretreatmentwith indomethecin, results in a proportionatelygreater increase in renal vascular resistance (28).We found that neither chronic salt loading norinfusion of l-Sar-8-Ala-angiotensin II in the postis-chemic period was able to decrease renal vascularresistance. Although these observations do notsupport a role for the renin-angiotensin system inthe production of the vasoconstriction, it is possiblethat intrarenal renin was not reduced completelyand that the antagonist was not reaching criticaleffector sites. Moreover, the changes seen may bethe result of other vasoconstrictors.

Of potential significance with regard to theincrease in renal vascular resistance is the relation-ship between other forms of obstruction to tubularflow and the delayed onset of preglomerular vaso-constriction (29). Flamenbaum et al. (30) havespeculated that a feedback mechanism betweenimpairment of tubular flow and intraglomerularfiltration pressure exists in rats studied 1 day afterbeing injected with 4.7 mg/kg of HgCl2 subcutane-ously. We have found (29) that 24 hours followingunilateral ureteral ligation both renal blood flowand estimated glomerular capillary hydrostatic



680 FINN. ARENDSHORST, GOTTSCHALK

pressure are significantly below control values—aresponse similar to that seen in our studies of acuterenal failure but without the complicating featuresof ischemia and tubular necrosis. In addition, whenindividual nephrons are obstructed with oil andstudied 24 hours later, estimated glomerular capil-lary hydrostatic pressure is reduced to a similarextent although adjacent, unobstructed nephronshave normal glomerular capillary hydrostatic pres-sures. Thus, there appears to be a delayed responseto tubular obstruction which is operative on anindividual nephron basis and which results inconstriction of afferent arterioles. An importantbut unproved corollary to this proposal is that thereturn of renal vascular resistance to normal levelswill occur following relief of intratubular obstruc-tion and reestablishment of tubular flow. For thisreturn to occur the tubular epithelium must regainits integrity. As intratubular pressure rises, tubularfluid flow increases and the stimulus to afferentarteriolar vasoconstriction lessens; these changesare followed by an elevation in glomerular capillaryhydrostatic pressure and a return of glomerularfiltration rate and renal blood flow to normalvalues.

Thus, our micropuncture studies of postischemicacute renal failure have clearly demonstrated thepresence of tubular obstruction, passive backflowof filtrate, and preglomerular vasoconstriction (Fig.1). Sequential studies have indicated that tubularobstruction is responsible for the generation of theoliguria and continues to be of prime importance inits maintenance. Analysis of the prolonged effectsof ureteral ligation and obstruction to individualnephrons supplies a link between the obstruction totubular flow and the development of preglomerularvasoconstriction. Although pathophysiological al-terations occur within the renal vasculature, weprefer not to use the term "vasomotor nephropa-thy" in describing this model, since the term tendsto obscure the contribution of other factors in boththe generation and the maintenance of the oliguria.Instead, we prefer to follow the classification ofOliver et al. (2) which describes the lesion interms of its etiological and morphological featuresas either ischemic or nephrotoxic acute renal fail-ure, recognizing that there is considerable overlapbetween the two.

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the renal tubule caused by certain poisons. Trans AssocAm Physicians 44:64-78, 1929

2. OLIVER J, MACDOWELL M, TRACY A: Pathogenesis of acute

renal failure associated with traumatic and toxic injury:

Renal ischemia, nephrotoxic damage and the ischemicepisode. J Clin Invest 30:1305-1351, 1951

3. FLAMENBAUM W: Pathophysiology of acute renal failure.Arch Intern Med 131:911-928, 1973

4. OKENDE: Modern concepts of the role of nephrotoxic agentsin the pathogenesis of acute renal failure. Prog BiochemPharmacol 7:1-29, 1971

5. OKEN DE: Nosologic considerations in the nomenclature ofacute renal failure. Nephron 8:505-510, 1971

6. WlEDERHIELM CA, WOODBURC. JW, KlRK S, RUSHMER RF:Pulsatile pressure in the microvasculature of the frog'smesentery. Am J Physiol 207:173-176, 1964

7. WUNDERLICH P., SCHNERMANN J: Continuous recording ofhydrostatic pressure in renal tubules and blood capillariesby use of a new pressure transducer. Arch Ges Physiol313:89-94, 1969

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tion of blood flow in the rat kidney. Am J Physiol228:127-133, 1975

9. FLANIGAN WJ, OKEN DE: Renal micropuncture study of thedevelopment of anuria in the rat with mercury-inducedacute renal failure. J Clin Invest 44:449-457, 1965

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globinuric acute renal failure in the rat: I. Micropuncturestudy of the development of oliguria. J Clin Invest45:724-735, 1966

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glomerular ultrafiltration in the rat. J Clin Invest50:1776-1780, 1971

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Dynamics of glomerular ultrafiltration in the rat: V.Response to ischemic injury. J Clin Invest 53:105-116,1974

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tubular fluid in anuria due to mercury poisoning. J ClinInvest 46:695-704, 1967

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tration of lissamine green in proximal tubules of antidiu-retic and mercury poisoned rats and the permeability ofthese tubules. PfluegersArch 311:1-15, 1969

18. TANNER GA, SLOAN KL, SOPHASAN S: Effects of renal arteryocclusion on kidney function in the rat. Kidney Int4:377-389, 1973

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24. EISENBACH GM, STEINHALSEN M: Micropuncture studiesafter temporary ischemia of rat kidneys. Pfluegers Arch343:11-25, 1973

25. REIMER KA, GANOTE CE, JENNINGS RB: Alterations in renalcortex following ischemic injury: III. infrastructure ofproximal tubules after ischemia or autolysis. Lab Invest26:347-363, 1972

26. MCGIFF JC, CROWSHAW K, TERRAC.NO NA, LONIC.RO AJ,STRAND JC, WILLIAMSON MA, LEE JB, NG KKF: Prosta-glandinlike substances appearing in canine renal venousblood during renal ischemia. Circ Res 27:765-789, 1970

27. MCGIFF JC, CROWSHAW K, TERRAC.NO NA, LONIC.RO AJ:Release of a prostaglandinlike substance into renal ve-nous blood in response to angiotensin II. Circ Res26(suppl I):I-121-130, 1970

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W F Finn, W J Arendshorst and C W GottschalkPathogenesis of oliguria in acute renal failure.

Print ISSN: 0009-7330. Online ISSN: 1524-4571 Copyright © 1975 American Heart Association, Inc. All rights reserved.is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Circulation Research

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