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Abstract: FR-PO541

Elucidating the Diuretic Effect of Corticosteroids in Rats

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Uema, Keito, Laboratory of Veterinary Pharmacology, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan
  • Sonoda, Hiroko, Laboratory of Veterinary Pharmacology, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan
  • Oguchi, Akane, Laboratory of Veterinary Pharmacology, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan
  • Higashijima, Yoshiki, Institute for Promotion of Tenure Track, University of Miyazaki, Miyazaki, Japan
  • Ikeda, Masahiro, Laboratory of Veterinary Pharmacology, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan
Background

Corticosteroids are widely used to treat kidney diseases such as nephrotic syndrome. A few cases of polyuria following corticosteroid treatment have been reported in human patients with heart failure or hypopituitarism. In dogs, corticosteroids frequently cause polyuria and polydipsia (Elkholly DA et al., Front Vet Sci. 2020). In experimental rat models, acute corticosteroid treatment is known to cause a potent diuretic effect (Tunhorst RL et al., Am J Physiol Regul Integr Comp Physiol 2007). However, the mechanisms by which corticosteroids cause polyuria is largely unknown. Here, we investigated the mechanism of corticosteroid-induced polyuria in rats treated with prednisolone (PSL).

Methods

Male SD rats aged 10 weeks were treated with PSL (0.3 or 1.0 mg/kg, s. c.) or vehicle (25% DMSO/75% Corn Oil, s. c.). Urine was collected for 6 hours after the treatment. Blood and kidneys were isolated at 6 hours post-treatment. The levels of electrolyte and osmolality in urine and blood were measured. Free water clearance was also calculated. The gene expression levels of sodium-dependent transporters and water channels were investigated by real-time PCR.

Results

The urine volume was significantly increased and the urinary osmolality was significantly decreased after the treatment of PSL, in a dose-dependent manner. The total excretion of Na+, K+, Cl- and inorganic phosphorus was significantly higher in rats treated with PSL than in without it. The free water clearance value was negative in the PSL-treated rats. Real-time PCR revealed that mRNA levels of sodium/chloride cotransporters (NKCC2/Slc12a1 and NCC/Slc12a3), sodium/phosphate cotransporters (Slc34a1 and Slc34a3) and a water channel (AQP2) were decreased in the PSL group. In addition, significant negative correlations were observed between urinary sodium excretion and the gene expression of NKCC2 and NCC.

Conclusion

These results indicate that reduced renal expression of sodium-dependent transporters in response to PSL may contribute to the suppression of electrolyte reabsorption, leading to the diuretic and natriuretic effects in rats. Since the free water clearance value was negative, the contribution of AQP2 was considered modest in the diuretic effect of PSL.