EFFECT OF CHRONIC TREATMENT WITH TRANDOLAPRIL OR ENALAPRIL ON BRAIN ACE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE RATS

The aim of the present study was to determine whether the new ACE inhi bitor trandolapril was able to inhibit brain ACE activity in spontaneo usly hypertensive rats (SHRs). Therefore, we have measured ex vivo ACE activity in discrete brain areas of SHRs after a 2-week oral treatmen t with trandolapril (0.001, 0.01, 0.1 and 1 mg/kg/day). The effects of trandolapril were compared to those of enalapril (10 mg/kg/day), used as a reference compound. Enalapril induced a decrease in ACE activity in brain areas not protected by the blood brain barrier (subfornical organ and median eminence) and in cerebral cortex. Conversely, trandol april at a dose of 0.01 mg/kg/day and above induced a dose-dependent i nhibition of ACE activity in all brain areas assayed, including the su praoptic and paraventricular hypothalamic nuclei, septum, amygdala, hi ppocampus, cerebellar and cerebral cortex, nucleus of the tractus soli tary and caudate nucleus. The inhibition was roughly similar in all br ain areas studied. These data suggest that after chronic oral administ ration in SHRs, trandolapril or its metabolite, in contrast to enalapr il or enalaprilat, was able to reach all brain areas of SHRs, includin g those protected by the blood brain barrier.