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

Abstract

SummaryThese experiments were undertaken to determine the differences between rats 3-4 and 7-8 wk of age with respect to the severity of acute renal failure (ARF) induced by two nephrotoxins, mercuric chloride (HgCI2) and uranyl nitrate (UN). Two observations suggested that the younger rats might be more susceptible to ARE ARF developed in response to a dose of HgC12, which had no effect in the older rats, and mortality rates tended to be higher in the younger rats. Despite this possible age-related difference in susceptibility, increased sodium intake (giving 1% NaCl rather than tap water to drink) had comparable protective effects in both models of nephrotoxin-induced ARF in rats of both ages. SpeculationDespite previously described age-related differences in the distal tubular handling of sodium, increased sodium intake resulted in qualitatively similar protection from nephrotoxic acute renal failure in both 3-4 and 7-Swk-old rats. Thus, the protective mechanism due to increased sodium intake may be a consequence of increased proximal tubular fluid flow.Despite intensive investigation, the pathogenesis of acute renal failure (ARF) remains controversial (5-1 1, 14-17, 23, 25-28, 34, 35, 37). A pathogenic role for the renin-angiotensin system has been postulated. This is based on the observations that, in certain experimental models of ARF, chronic sodium (Na) and potassium (K) loading suppress renal renin and reduce the severity of ARF whereas chronic Na deprivation augments renal renin and enhances the severity of ARF (14). Although we have confirmed that the severity of nephrotoxic ARF is inversely related to dietary Na intake and/or excretion, we have shown that this relationship is independent of changes in renal renin, at least in the mature rat (5). Very few data concerning ARF in the immature rat are available. Studies using the developing animal might provide some insights, inasmuch as there are.age-related differences in the activity of the renin-angiotensin system and in the ability to handle volume expansion and dietary Na loads in many species, including the rat (1, 3-5,6, 18-21, 24, 32, 33). Any of these factors might affect the susceptibility to and/or the severity of ARF.In a previous study of 2-, 4-and 8-wk-old rats, no pattern was found between the severity of mercuric chloride-induced ARF and either basal renal renin, plasma renin, or the increase in plasma renin 6 h after injection. However, there were age-related differences: mortality was highest in the 2-wk olds, and those that survived exhibited a delayed recovery, similar to what has been found in mature rats subjected to Na deprivation (5).In the present studies, younger (34-wk old) and older (7-8-wk old) rats were compared with respect to the effect of varying dietary Na on two nephrotoxic models of ARF: mercuric chloride (HgC12) and uranyl nitrate (UN). In addition, the dose-response to HgCl2 of these two age groups were compared. It should be noted that since the weaning age of rats is 18-20 days, the younger rats of these studies ...

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.…”

“…Sections stained with uranyl acetate and lead citrate, ~1 6 0 0 . 6. Midcortical region of a kidney from an older puppy (25-day-old) 24 h after uranyl nitrate administration.…”