BACKGROUND: Patients premedicated with clonidine often present with hypotension and bradycardia. The hypotensive patient premedicated with clonidine should be given a vasopressor to treat hypotension. In these patients, an augmented vasopressor response would be shown. Rilmenidine as an allied drug of clonidine is an antihypertensive agent with selectivity for the imidazoline receptor that acts centrally by reducing sympathetic overactivity. This study was designed to evaluate the effect of clonidine and rilmenidine on changes in mean blood pressure and baroreflex sensitivity following phenylephrine and nitroprusside administration. METHODS: Sixty Sprague-Dawley rats were assigned randomly into one of three groups, control group (n = 20), clonidine group (n = 20) or rilmenidine group (n = 20). Saline (control group), clonidine 30ng/kg (clonidine group) or rilmenidine 300ng/kg (rilmenidine group) were intraperitoneally injected respectively. Following the injection, a phenylephrine and nitroprusside test were performed. RESULTS: The percent change in mean blood perssure from the baseline values in the control group, clonidine group and rilmenidine group were 35 +/- 18%, 54 +/- 17% and 62 +/- 38%, respectively. There was no difference between the baroreflex sensitivity in the pressure (phenylephrine) test (0.94 +/- 0.43, vs 1.05 +/- 0.62, vs 1.13 +/- 0.59 msec/mmHg). In contrast, the slopes of the depressor (nitroprusside) test were decreased in rats receiving clonidine and rilmenidine (0.51 +/- 0.34, vs 0.12 +/- 0.08, vs 0.18 +/- 0.09 msec/mmHg, P < 0.05). CONCLUSIONS: It is concluded that the rilmenidine and clonidine groups showed a more augmented pressure response to vasopressors than the control group. Therefore, the decreased dosage of vasopressors is recommended to treat hypotension in rilmenidine premedicated patients.