Effect of ramipril [HOE 498] on the central monoaminergic system in normotensive and doca-salt hypertensive rats

ABSTRACT

Acute and chronic effects of ramipril in normotensive and DOCA-salt hypertensive rats, respectively, were investigated on the brain monoaminergic system and the renin-angiotensin system [RAS]. Acute ramipril treatment in normotensive rats produced a significant drop in plasma angiotensin converting enzyme [ACE] and brain monoamine oxidase [MAO] activities accompanied by a significant rise in brain 5-hydroxytryptamine [5-HT] level. Changes in brain catecholamines [CA]; namely, norepinephrine [NE] and dopamine [DA], were insignificant, possibly pointing to a longer duration of action needed by ramipril to exert its direct control inhibition on the sympathetic tone. On the other hand, chronic ramipril treatment in DOCA-salt hypertensive rats produced a significant drop in plasma ACE and brain MAO associated with a significant rise in brain NE, DA and 5-HT levels, the blood pressure and heart rate values were also controlled to reach nearly normal values. These data suggested that chronic administration of ramipril might have partly diminished secondary sympathetic activity and slowed down brain CA and 5-HT turnover. Moreover, the data emphasize the modulating role of the RAS on central sympathetic activity during both the normotensive and the hypertensive and the hypertensive states