Administration time-dependent change in the effect of spironolactone in rats

The present study was undertaken to examine whether the natriuretic effect of spironolactone, a competitive antagonist of mineralocorticoid, varies with its time of administration. Wistar rat maintained under the condition of light from 7 hr to 19 hr were divided into two groups. The first group had a bilateral adrenalectomy and received a 50-mg deoxycorticosterone acetate (DOCA) tablet intraperitoneally (DOCA group). The second group had a sham operation (control group). Spironolactone (50 mg/kg) was given orally at 12 hr or 24 hr, and the 8-hr urine was collected. At the end of the experiment, the blood sample for measurement of aldosterone was obtained at 12 hr and 24 hr in the control group. The natriuretic effect of spironolactone in the 24 hr-trial was significantly greater than that of the 12 hr-trial in the control group. However, such a time-dependent difference was diminished and did not reach statistical significance in the DOCA group. The plasma aldosterone concentration at 24 hr was significantly higher than that at 12 hr in the control group. These results suggest that the natriuretic effect of spironolactone varies with its time of administration. Daily variation in mineralocorticoid activity might be involved in this chronopharmacological phenomenon of spironolactone.