Comparative effects of the two angiotensin converting enzyme inhibitors perindopril and ramipril on brain dopamine content in rats

ABSTRACT

The existence of brain rennin-angiotensin system [RAS] is well established and it may affect cognitive function and movement disorders. It has been suggested that manipulation of brain angiotensin could be a new therapeutic tool to modulate brain dopamine level, abnormalities of which are implicated in a wide range of conditions including extrapyramidal movement disorders, depression, appetite control, schizophrenia and arousal. In this work, we studied the changes in behavior and brain dopamine content under the effect of two lipophilic ACEIs, perindopril and ramipril, used orally daily for one week in normal rats. Other rat groups were then given single subcutaneous reserpine injection [5 mg/kg] to study the effect of pre-treatment with the ACEIs on the reserpine-induced akinesia, neurobehavioral changes and depleted brain dopamine. In normal rats, although perindopril increased dopamine content in the three brain regions examined, ramipril had no effect on striarum but there were no significant differences between the two ACEIs in their effects on frontal cortex and midbrain. Neither perindopril nor ramipril caused neurobehavioral effects. Both drugs reduced the reserpine-induced akinesia and behavioral changes and antagonized the reserpine-induced brain dopamine depletion. We concluded that chronic ACEIs therapy can influence dopamine level and this is a class effect depending on tissue penetration and crossing BBB