Influence of DOCA treatment on administration-time-dependent changes in the effects of furosemide in saline-loaded rats.

We have previously found that the administration-time-dependent change in the effects of furosemide, a loop diuretic agent, is observed in normal rats. The present study was undertaken to examine whether an alteration in this phenomenon occurs in rats with DOCA-saline hypertension. Unilateral nephrectomized rats were divided into three groups. The first group (DOCA-saline) received a 50 mg DOCA tablet intraperitoneally and drank 1% NaCl solution. The other two groups were given sham operations. A 1% NaCl solution was given as drinking water to the second group (control-saline), while tap water was given to the third group (control-water). Furosemide (30 mg/kg) was given orally to each group at 12 a.m. or 12 p.m. Urine was collected for 8 hours after the agent, and urinary excretion of sodium and furosemide were determined. Urine volume and urinary excretion of sodium and furosemide following the agent were significantly greater at 12 a.m. than at 12 p.m. in the control-water and control-saline groups. However, the administration-time-dependent changes in these parameters disappeared in the DOCA-saline rats. These results suggest that the mode of the administration-time-dependent changes in the effects of furosemide is altered in the DOCA-saline hypertensive rats.