The oliguria of acute renal failure has been attributed to tubular obstruction (1-12), "leakage" of the glomerular filtrate through rents in the tubular wall (13)(14)(15)(16)(17)(18)(19), and vascular mechanisms of various types (20)(21)(22)(23)(24)(25). In a previous paper, it was shown that the oliguria of mercury-induced acute renal failure in the rat reflects a primary decrease in glomerular filtration rate and cannot be attributed to tubular mechanisms (26). The applicability of these findings to most types of acute renal failure occurring in humans may be questioned, however, because of the very dissimilar etiologies and the known effect of large doses of mercury on the renal circulation (27). The present study concerns hours before glycerol injection. They lost an average of 8% of body weight in the period of dehydration, during which time their food intake was one-third less than that of nondehydrated animals. Blood samples were obtained by cardiac puncture from a number of glycerolinjected animals and dehydrated control rats that were exempted from micropuncture studies to determine the change in their blood urea nitrogen (BUN) occurring over a 48-hour period. BUN was measured on 0.2-ml samples by a modification of the urease method of Gentzkow (28). Urinary osmolalities were determined with an Advanced osmometer.Acute renal failure was induced by injecting 50%o glycerol in water into the muscle of both hind limbs at a total dose of 10 ml per kg of body weight. Within 2 hours after this injection, the urine was found to be burgundy red in color due to the presence of heme pigments.The animals were subjected to micropuncture experiments at times ranging from 30 minutes to 26 hours after glycerol injection. They were anesthetized with sodium pentobarbital given intraperitoneally at a dose of 40 to 50 mg per kg body weight. Their blood pressure was monitored as described earlier (26) either by a tail cuff microphone method or intra-arterial manometry. Although hypotension typically did not occur, animals whose mean arterial blood pressure was less than 85 mm Hg were excluded from micropuncture study. The left kidney was exposed through an abdominal incision and carefully dissected free of the perirenal fat. The renal hilus was disturbed as little as possible, and the renal capsule was left intact. The kidney was placed in a Lucite holder to minimize its displacement with respiration. Its surface was covered with warm mineral oil to prevent drying and to aid in visualization of the renal structures.Micropuncture methods were those described in an earlier paper (26). In short, proximal tubular hydrostatic pressure was measured by a modification of the manometric method of Wirz (29), using a water manometer to obtain maximal definition of the end point. The manometer was calibrated at zero pressure before each measurement. Glomerular filtration rate and fractional water absorption were determined at least 30 minutes after the injection of 40 ,uc of "C-labeled inulin 1 in 0.3 to 0.5 ml of 140 mM NaCl. Labele...

The role of the concentrating mechanism in the potentiation of acute renal failure by dehydration has been studied using rats with complete diabetes insipidus. These rats were shown to be continually dehydrated even when allowed free access to water. Despite massive volumes of highly dilute urine at the time that hemoglobinuria was induced by glycerol injection, these animals developed acute renal insufficiency whose severity was intermediate between that of non-dehydrated and severely dehydrated normal rats treated similarly. Micropuncture experiments showed the appearance of the kidney in vivo and the functional abnormalities of the three types of rats to be qualitatively identical. It appears that dehydration’s effect on hemoglobinuric acute renal failure is independent of the concentrating mechanism and correlates well with plasma volume depletion. It is suggested that factors other than ADH titre, high urine concentration and low flow rate are the prime determinants of the effect of dehydration on hemoglobinuric acute renal failure in the rat.

Hemoglobinuric acute renal failure occurs consistently in rats deprived of water for 24 h and injected with 50% glycerol solution (10 ml/kg) intramuscularly. Severe azotemia developed in 33% of non-dehydrated rats receiving glycerol but 44% were not azotemic, thus permitting a study of the factors which predispose to the development of acute renal failure. There was no necessary correlation between urine volume, urine osmolality, or plasma volume before injection and the development of oliguric acute renal failure, nor was the urine pH during hemoglobinuria correlated with the subsequent severity of azotemia. Plasma volume depletion was the only major difference detected between dehydrated rats which universally developed severe acute renal failure and non-dehydrated rats which were frequently spared. Small differences in plasma volume did not appear to alter the severity of renal involvement in non-dehydrated rats, however.

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