Effect of Captopril on the-Dependent Variation of Kaolin-Induced Writhing Reaction

Effect of captopril, an angiotensin-converting enzyme (ACE) inhibitor, on the time-dependent variation of kaolin-induced writhing reactions was examined in mice kept under conditions of light from 07: 00 to 19: 00 and dark from 19: 00 to 07: 00. The number of writhes was counted for 60 minutes after a single intraperitoneal injection of kaolin at 01: 00, 07: 00, 13: 00, and 19: 00. The number of writhes showed a time-dependent variation, with a peak at 19: 00 and a trough at 07: 00 in the control group. Captopril significantly increased the number of writhes after dosing at 01: 00 and 07: 00 (during the active period). The ACE activity following captopril dosing was significantly lower in the 07: 00 than the 19: 00 trial. These results suggest that the pharmacological effect of captopril varies with the dosing time, and the enhancement of the kaolin-induced writhing reaction is greater following dosing of the agent at nighttime in mice.