HgCl2-induced acute renal failure in the developing rat.

The present investigation was undertaken to find the differences, if any, in the pattern of nephrotoxic acute renal failure (HgCl2, 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 HgCl2, 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 recovery (blood urea nitrogen began to decline), whereas blood urea nitrogen 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.

HgCl2-induced acute renal failure in the Goldblatt rat.

These experiments were designed to test the hypothesis that renal renin is an important determinant of the severity of acute renal failure in rats. Two-kidney "Goldblatt rats" were prepared by constricting the left renal arteries with silver clips and leaving the contralateral arteries untouched. After 2 to 5 weeks, the clips were removed, and HgCl2 was injected in 13 rats (1 ml/kg body weight of 4.7 mg of HgCl2 per milliliter of 140 mM NaCl). These rats exhibited the characteristic features of acute renal failure 24 hr later. As compared with a group of seven similarly treated rats injected with 140 mM NaCl without HgCl2, GFR, V, and UNaV were reduced, and %FE H2O and %FE Na were increased. As assessed by these parameters, severity of functional impairment was equal in both kidneys. However, cortical renin was 28 times higher in the left kidney than in the right. These results are inconsistent with the hypothesis.

Natriuresis-induced protection in acute myohemoglobinuric renal failure without renal cortical renin content depletion in the rat.

The interrelationships of renal cortical renin content RCRC, sodium chloride excreting and the severity of renal failure were studied in the glycerol-induced acute myohemoglobinuric renal failure model in the rat. Protocols were designed to increase sodium chloride excretion without necessarily resulting in RCRC depletion. Our data fail to demonstrate a relationship between RCRC and severity of renal failure, but they demonstrate an excellent inverse correlation between the sodium chloride excretion of the animals in the 24 h prior to glycerol administration and the severity of resulitng renal failure. The protection of long-term saline-drinking animals should properly be ascribed to the associated natriuresis which develops much before RCRC depletion during the time course of saline drinking. The exact mechanism by which natriuresis exerts its protective effect needs further elucidation, but our data argue against a major role for RCRC in the pathogenesis of acute experimental renal failure.

Glycerol-induced acute renal failure in the two kidney Goldblatt rat.

One to four weeks after the left renal artery was clipped and the contralateral kidney was left untouched in Sprague-Dawley rats (two-kidney Goldblatt preparation), the clips were removed under ether anesthesia and 10 ml/kg body wt of either 150 mM NaCl (control) or 50% glycerol in water (experimental) were injected intramuscularly. The next day the rats were anesthetized (sodium pentobarbital) and the renal function of both kidneys was measured, after which the renal cortical renin content was measured by incubation of tissue homogenate with angiotensinase-free rat renin substrate. Radioimmunoassay was used to determine the rate of angiotensin I production. Compared with controls, both kidneys of glycerol-injected rats had reduced GFR (left 28, right 18% of controls), increased percentage of fractional water excretion (left 5, right 6 times controls), and increased percentage of fractional Na excretion (left 3, right 4 times controls). Despite large differences in renal renin (left 28, 676, right 1,329 ng angiotensin I/h per mg protein), the extent of renal failure produced by glycerol was equal in the left and right kidneys. These results are inconsistent with the hypothesis that renal renin content is directly related to the severity of glycerol-induced renal failure in rats.