Rapid effect of dexamethasone on the permeability of visceral sheep peritoneum

Abstract

The peritoneal mesothelium is a biologic barrier to water and ion transport. Its functional and structural integrity is crucial for peritoneal dialysis treatment. In vivo studies have shown that corticosteroids increase transcellular water transport and ultrafiltration of the rat peritoneum. In the present study, we used Ussing chamber technique to investigate the effect of dexamethasone on the transmesothelial permeability of the visceral sheep peritoneum in vitro. Peritoneal samples from the omentum of adult sheep were collected in a cooled and oxygenated Krebs-Ringer bicarbonate (KRB) solution immediately after the death of the animals. Isolated intact sheets were mounted in an Ussing-type chamber. Dexamethasone (10(-6) mol/L) and its inhibitor mifepristone (10(-5) mol/L) were added apically and basolaterally, alone and in combination to the KRB solution. The transmesothelial resistance (R) was measured for 1 hour before and serially after the addition of the substances. Data are expressed as mean +/- standard error of 6 experiments in each case. The control R was 21.5 +/- 0.42 omega x cm2. Dexamethasone induced a significant reduction of R within 15 minutes, which continued for the entire experiment. The maximum effect (% deltaR) was observed at 30 - 60 minutes after the addition of dexamethasone apically 46.2% +/- 7.14% (p < 0.01) and basolaterally 35.3% +/- 7.76% (p < 0.01). Mifepristone acted as an agonist on both sides of the membrane and significantly inhibited the dexamethasone effect. Our findings clearly indicate that dexamethasone rapidly increases the transmesothelial permeability of visceral sheep peritoneum. The rapid effect implicates dexamethasone and probably mifepristone as being involved in a common nongenomic pathway. Further investigation is necessary to elucidate the underlying mechanisms and perspectives of these findings.