ANGIOTENSIN-CONVERTING ENZYME MODULATES DOPAMINE TURNOVER IN THE STRIATUM

The effect of chronic inhibition of the angiotensin-converting enzyme on dopamine content and release in the striatum was investigated using in vivo microdialysis in awake, freely moving rats. Rats were treated for 1 week with the angiotensin-converting enzyme inhibitor perindopr il (1 mg/kg) via the drinking water, whereas the controls were given w ater alone. One week after perindopril treatment, striatal dopamine di alysate levels in the treated group were markedly elevated compared wi th control values: control, 233 +/- 43 pg/ml; perindopril, 635 +/- 53 pg/ml (p < 0.001). These results were confirmed by a complementary stu dy in which dopamine content was measured in striatal extracts (3.5 +/ - 0.4 mu g of dopamine/g of tissue for controls compared with 9.2 +/- 2.4 mu g of dopamine/g of tissue for the treated group; p < 0.05). In the rats that were dialyzed, angiotensin-converting enzyme levels in t he striatum were decreased by 50% after perindopril treatment. Levels of dopamine D-1 and D-2 receptors and of preprotachykinin and tyrosine hydroxylase mRNAs were unchanged after angiotensin-converting enzyme inhibition. A small, but significant, increase was detected in striata l preproenkephalin mRNA levels in the angiotensin-converting enzyme in hibitor-treated group, These results indicate that peripherally admini stered angiotensin-converting enzyme inhibitors penetrate the blood-br ain barrier when given chronically and modulate extracellular dopamine and striatal neuropeptide levels.