In this study, we characterized the sequence of several intrarenal events and evaluated their relative importance in the pathogenesis of unilateral oliguric acute renal failure induced experimentally in rats by complete occlusion of a renal artery for 1 hour. Kidneys were studied prior to occlusion and 1-3 hours and 22-26 hours after release of the temporary occlusion. Renal blood flow measured by an electromagnetic flow transducer was reduced to 40-50% of control during both postocclusion periods. Flow of tubular fluid was markedly reduced, and the damaged kidneys were oliguric. Proximal and distal convolutions were filled with fluid and dilated 1-3 hours after occlusion; their pressures were greatly heterogeneous and were elevated, on the average, to 31 and 16 mm Hg, respectively. Glomerular capillary pressure at this time was normal or slightly increased. Histological sections showed extensive tubular obstruction. We conclude that initially the oliguria is primarily due to intraluminal obstruction in the absence of predominant increases in preglomerular vascular resistance. Observations at 22-26 hours after occlusion indicated acute tubular necrosis. Moreover, the combined involvement of preglomerular vasoconstriction, persisting tubular obstruction, and passive backflow of tubular fluid appeared to be important in the maintenance of the oliguria. Glomerular capillary, proximal intratubular, and peritubular capillary hydrostatic pressures were reduced below control values. After acute volume expansion, the reduced pressures and renal blood flow were reversed, yet the experimental kidneys remained oliguric. Thus, it is clear that tubular obstruction is a significant factor responsible for both the genesis and the maintenance of oliguria in this experimental model of ischemia-induced acute renal failure.• A controversy concerning the nature and sequence of events involved in the development and maintenance of oliguria in acute renal failure persists despite the application of a number of investigative techniques in a variety of experimental models. Studies of acute renal failure have been performed in an attempt to determine the relative importance of the following etiologic factors: (1) primary failure to filter fluid across glomerular membranes which might result from arteriolar vasomotor changes lowering glomerular capillary pressure or plasma flow or from reductions in the glomerular ultrafiltration coefficient, (2) This investigation was supported in part by a grant-in-aid from the American Heart Association, by U. S. Public Health Service Grant HE-02334 from the National Heart and Lung Institute, by NIH Training Grant 5 T01 AM05054, and by Grant 1973-74-A-36 from the North Carolina Heart Association.Dr. Gottschalk is a Career Investigator of the American Heart Association.A preliminary report of this work was presented to the 6th Annual Meeting of the American Society of Nephrology, Washington, D. C, November, 1973. Received April 21, 1975. Accepted for publication July 17. 1975. 558epithelium. ...

We present evidence showing that renal blood flow (RBF) in the anesthetized nondiuretic rat can be measured reliably and accurately using a noncannulating flow transducer and an electromagnetic flowmeter. In vitro calibration yielded a linear relationship (r=0.998) between flowmeter output voltage and blood flow rates from 0.2 to 10.3 ml/min. Excellent agreement was observed between simultaneous determinations of RBF by the flowmeter and the PAH clearance technique. Glomerular filtration rate and RBF for a kidney with a flow transducer around its renal artery did not differ significantly from corresponding values for the undisturbed contralateral kidney. The relationship of mean RBF with steady-state variations in perfusion pressure was evaluated in 13 nondiuretic rats. RBF averaged 6 ml/min.g kidney wt at arterial pressures (AP) above 100 mmHg. A high degree of autoregulatory efficiency was observed when mean AP varied between 105 and 145 mmHg. Over this pressure range RBF changed only 3% as changes in intrarenal vascular resistance and AP were directly related (r=0.994). Below 95-105 mmHg RBF decreased in a curvilinear fashion with the concavity toward the pressure axis.

Using a small-diameter electromagnetic flow transducer, the effect on the autoregulation of renal blood flow (RBF) of two structurally different prostaglandin synthetase inhibitors, indomethacin, 4 mg/kg BW, and meclofenamate, 5 mg/kg BW, was studied in nondiuretic rats anesthetized with either the oxybarbiturate, sodium pentobarbital, or the thiobarbiturate, Inactin. Regardless of the anesthetic agent, RBF remained relatively constant above a perfusion pressure of 105 mmHg. Treatment with either indomethacin or meclofenamate had no measurable effect on the autoregulatory response. Each agent, however, resulted in an increase in the renal vascular response to exogenous angiotensin II, an effect consistent with prostaglandin synthetase inhibition. Base-line RBF was significantly reduced by indomethacin or meclofenamate only in those animals that had previously received angiotensin. These results support the hypothesis that, in th rat, autoregulation of RBF occurs independently of prostaglandin activity, but that a relationship does exist between the renal vascular actions of angiotensin II and prostaglandins.

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