ABSENCE OF TOLERANCE TO HYPOTENSIVE EFFECTS OF CLONIDINE IN SPONTANEOUSLY HYPERTENSIVE RATS

Development of tolerance to the hypotensive effects of clonidine was investigated in spontaneously hypertensive rats (SHR). Clonidine (125 mu g/kg/day) was administered subcutaneously for 5 weeks using an osmotic infusion pump. During the whole infusion period, significant hypotensive and bradycardic effects were observed. Plasma clonidine concentrations were maintained relatively constant at about 2 ng/ml during the infusion period. On termination of treatment with clonidine, both the blood pressure and heart rate rapidly recovered to the control levels. These findings suggest that clonidine does not cause tolerance to its hypotensive effects in SHR with the present administration regimen.