Studies on the pathophysiology of acute renal failure - V. Effect of chronic saline loading on the progression of proximal tubular injury and functional impairment following administration of mercuric chloride in the rat

J. L. Barnes, E. M. McDowell, J. S. McNeil, W. Flamenbaum, B. F. Trump

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25 Scopus citations


Studies were performed to investigate the effect of chronic saline loading on the progression of mercuric chloride (HgCl2)-induced morphological and histochemical changes in rat proximal tubules and the degree of impaired renal function, between 0.5 h and 48 h after administration of the nephrotoxin. Saline drinking rats (NaCl) showed no significant changes in creatinine clearance (CCr) or blood urea nitrogen concentration (BUN) when compared to water drinking control rats (H2O). However, HgCl2, when given to water drinking rats (H2O-HgCl2) produced a non-oliguric form of acute renal failure (ARF), characterized by increased fractional excretion of sodium (FENa+), reduction in CCr and azotemia. Saline drinking rats given HgCl2, (NaCl-HgCl2) were markedly protected against HgCl2-induced functional impairment as indicated by maintenance of CCr and BUN closer to control values when compared to H2O-HgCl2 rats. Administration of HgCl2 to rats in both groups (H2O-HgCl2 and NaCl-HgCl2) produced similar degrees of proximal tubular injury, as demonstrated by light and electron microscopy and enzyme histochemistry. Dispersion of cytoplasmic ribosomes occurred initially (0.5, 1 and 3 h), particularly in proximal convoluted tubules. In addition, increased numbers of small apical tubules and dense bodies were noted in the pars convoluta of both groups at 3 h following HgCl2. By 6, 12, 24 and 48 h, injury to the first portion of the pars convoluta (P1) tended to be reversible. The more terminal portion of the pars convoluta (P2) of H2O-HgCl2 rats showed numerous small apical vacuoles, focal loss of brush border and widespread dispersion of cytoplasmic ribosomes at 6 h, and progressed to more advanced injury, including necrosis, at 24 h following administration of HgCl2. Changes were similar but slightly less advanced in P2 of NaCl-HgCl2 rats at these time intervals. However, by 48 h, rats from both HgCl2-treated groups showed sublethal changes and regeneration in P2 in some rats while in others this segment was necrotic. All proximal tubules of the pars recta (P3) of rats from both groups showed complete necrosis at 24 h and 48 h. Activities of alkaline phosphatase and acid phosphatase were reduced in P1 and P2, at 1 h following HgCl2 in rats of both groups. 5′-nucleotidase and succinate dehydrogenase were reduced at 3 h. Enzyme activities remained below control levels throughout the time course of study and reductions in activities in both groups followed the same general trend. However, activities varied between groups depending on the particular enzyme studied, the time interval and the tubular portion in question. Activities of all enzymes studied in P3 of both groups were minimal at 24 h and 48 h following HgCl2. The results of this study support the role of the renin-angiotensin system in the pathophysiology of ARF. It is hypothesized that in H2O-HgCl2-renin intact rats, HgCl2-induced alterations in proximal tubular handling of electrolytes lead to an increased concentration of Na+ and Cl- at the macula densa which leads to the local release of renin, vasoconstriction of the afferent arteriole and subsequent filtration failure. Since chronic NaCl loading results in depletion of intrarenal renin. NaCl-HgCl2 rats are protected against the development of ARF, despite proximal convoluted tubular injury and its resultant dysfunction, because in this case changes in electrolyte concentration cannot trigger the renin-angiotensin system.

Original languageEnglish (US)
Pages (from-to)233-260
Number of pages28
JournalVirchows Archiv B Cell Pathology Including Molecular Pathology
Issue number1
StatePublished - Dec 1980
Externally publishedYes


  • Acute renal failure
  • Enzymes
  • Mercuric chloride
  • Proximal tubule
  • Saline loading

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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