HgCl2-induced Acute Renal Failure in the Developing Rat

Abstract

SummaryThe present investigation was undertaken to find the differences, if any, in the pattern of nephrotoxic acute renal failure (HgCI2, 4.7 mg/kg body weight SC). in the developing rat and its relationship to the renin angiotensin system. No differences in renal cortical renin content were found between 2. 4, and 8 week olds, but plasma renin concentration was highest at 2 weeks and declined with age. Plasma renin was significantly increased in all groups 6 hr after HgCl2 injection, and the percentage of increase was highest in the 4 week olds. Despite these differences in initial plasma renin and in changes in plasma renin after HgCI2, the pattern of acute renal failure (as assessed by changes in blood urea nitrogen) was similar in the three groups for the first three days. Subsequently, the 4 and 8 week olds exhibited recoverv ( b i d urea nitrogen began to decline), wheras blood urea nitrogeh continued to increase to the fifth day in the 2 week olds. The mortality was highest in this group. No simple correlation was observed between basal renal renin, plasma renin, the increase in plasma renin following HgCl2 injection, and the pattern or severity of acute renal failure.volumes were recorded for the duration of the study. The urine collected for the 24 hr preceding the experiment was analyzed for Na'. K ' . and C1-. On the morning of the experiment, a tail vein blood sample was obtained from the 8-week-old animals for control BUN. Then HgC12 was administered SC (4.7 mg HgCI2 per ml 140 mM NaCI, I ml/kg body weight), and BUN determinations were repeated I, 2, 3, 5, and 7 days later.Because of the possible deleterious effect of initial blood sampling in the 4-week-old animals, only one-third of this group had a baseline BUN determination. Then the group was divided into 2 subgroups: those that had BUN determinations on days 1, 3, 5, and 7 and those that had BUN determinations on days 2, 5, and 7. Although somewhat higher BUN values were observed in those which had an initial tail vein sample drawn, the results were not significantly different from those which did not.The 2-week-old pups were allowed to stay with their mothers because the weaning age in rats is approximately 3 weeks. Random animals were sacrificed from the litters for baseline BUN values, and the rest received HgC12 as stated above. Because of the difficulty of obtaining serial samples in these small animals, random DUDS were sacrificed for BUN determinations on days I, 2, 3, 4, '5,'and 7. To follow body weight changes as weil as Speculation mortality, renal failure was induced in additional litters of 2-week-The delayed recovery of renal function in younger rats may be old pups. Survivors of this group were sacrificed at 7 days for due to a limitation in their ability to eliminate nephrotoxin imposed BUN determinations. Mean body weight of this group was comby immaturity of both glomerular and tubular function. pared with that found in other litters of 2-week-old pups which had received NaCl(140 mM: I ml/kg) rather than HgCI2. . -Urinary Na'...

Effects of Sodium Intake and Nephrotoxin Dose on Acute Renal Failure in the Young Rat

“…However, the similar values of % increase in BUN/% increase in Scr in rats of both age groups suggest that, short of measuring changes in glomerular filtration rate directly, the use of BUN as an index is not inappropriate. It is of interest that, whether mortality or BUN is used as an index of susceptibility or severity, the differences between the 3 4 -and the 7-8-wk-old rats of the present study were less dramatic than those observed previously between 2-and 8-wk-old rats (6). Following the 4.7 mg/kg dose of HgCl*.…”

“…Thus, it is impossible to draw firm conclusions concerning the % of dietary Na and K excreted in the urine. However, it is likely that food intake per unit body weight was higher, and therefore that Na and K intakes were higher, in the younger rats during this period of rapid weight gain (3,4,6). This might explain why all groups of ybunger rats excreted more K than the corresponding groups of older rats and why the younger rats fed the normal Na diet excreted more than twice as much Na as the older rats.…”

“…Methods for measurement of urinary Na and K, BUN and SC, have been described in recent publications from this laboratory (5)(6)(7)(8)10).…”

The Influence of Age on Acute Renal Toxicity of Uranyl Nitrate in the Dog

“…In contrast, Bidani el a/. (5,6) evaluating UN and HgC1,-induced ARF in developing rats obtained conflicting results: the degree of ARF was similar in all age groups and a pattern of delayed renal function recovery and higher mortality rate was exhibited by the youngest animals.…”