Excretion of electrolytes in Brown Norway and Fischer 344 rats: effects of adrenalectomy and of mineralocorticoid and glucocorticoid receptor ligands

Exp Physiol. 2004 Nov;89(6):753-65. doi: 10.1113/expphysiol.2004.028621. Epub 2004 Sep 13.

Abstract

Our previous studies showed that adrenalectomy (ADX) has surprisingly no effect on body weight and fluid intake in the Brown Norway rat strain, suggesting that mineralocorticoid receptor (MR)-mediated effects are present even in absence of corticosteroids in this strain. Moreover, glucocorticoid receptor (GR)-mediated mechanisms are more effective in Brown Norway than in Fischer 344 rats. Such functional differences in corticosteroid receptor pathways between Brown Norway and Fischer 344 rats led us to compare the effect of ADX and MR/GR-mediated actions on sodium and potassium excretion between these two rat strains. To this end, we first measured the effect of an acute high dose of aldosterone on the urinary Na+/K+ concentration ratio in intact and ADX Brown Norway and Fischer 344 rats. Second, to discriminate mineralocorticoid from glucocorticoid actions, we treated chronically ADX rats with increasing doses of aldosterone or RU28362, a pure GR agonist, in the drinking fluid. As sodium homeostasis involves salt appetite regulation, behaviour under mineralocorticoid control, we also measured saline preference in Brown Norway and Fischer 344 rats. Our data illustrate: (1) the very limited effect of ADX on body weight, food and fluid intake, diuresis, natriuresis, kaliuresis and salt appetite in Brown Norway rats, supporting the presence of MR signalling pathways in the absence of adrenal steroids in these rats; (2) the insensitivity of MR to aldosterone in intact Brown Norway rats, and the reduced sensitivity of MR to aldosterone in ADX Brown Norway rats compared with ADX Fischer 344 rats; and (3) the greater sensitivity of GR-related mechanisms to RU28362 in Brown Norway than in Fischer 344 rats in terms of body weight gain and electrolyte excretion. Considering that both MRs and GRs regulate hypothalamic-pituitary-adrenal axis processes, such functional differences in corticosteroid receptors could be at the origin, at least partly, of the strain differences in corticotropic activity/reactivity to stress previously described.

MeSH terms

  • Adrenalectomy*
  • Aldosterone / administration & dosage
  • Aldosterone / pharmacology
  • Animals
  • Appetite
  • Body Weight
  • Diuresis
  • Dose-Response Relationship, Drug
  • Drinking
  • Drug Administration Schedule
  • Eating
  • Electrolytes / urine*
  • Ligands
  • Male
  • Osmolar Concentration
  • Potassium / urine
  • Rats
  • Rats, Inbred BN / anatomy & histology
  • Rats, Inbred BN / urine*
  • Rats, Inbred F344 / anatomy & histology
  • Rats, Inbred F344 / urine*
  • Receptors, Glucocorticoid / metabolism*
  • Receptors, Mineralocorticoid / metabolism*
  • Roxithromycin / administration & dosage
  • Roxithromycin / pharmacology
  • Sodium / urine
  • Sodium Chloride
  • Species Specificity

Substances

  • Electrolytes
  • Ligands
  • Receptors, Glucocorticoid
  • Receptors, Mineralocorticoid
  • Roxithromycin
  • Sodium Chloride
  • Aldosterone
  • Sodium
  • Potassium