Angiotensin-Converting Enzyme Modulates Dopamine Turnover in the Striatum
Article first published online: 18 NOV 2002
Journal of Neurochemistry
Volume 68, Issue 3, pages 1304–1311, March 1997
How to Cite
Jenkins, T. A., Mendelsohn, F. A. O. and Chai, S. Y. (1997), Angiotensin-Converting Enzyme Modulates Dopamine Turnover in the Striatum. Journal of Neurochemistry, 68: 1304–1311. doi: 10.1046/j.1471-4159.1997.68031304.x
- Issue published online: 18 NOV 2002
- Article first published online: 18 NOV 2002
- Received May 21, 1996; revised manuscript received September 25, 1996; accepted November 12, 1996.
- Angiotensin-converting enzyme;
- Angiotensin-converting enzyme inhibitor;
Abstract: 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 perindopril (1 mg/kg) via the drinking water, whereas the controls were given water alone. One week after perindopril treatment, striatal dopamine dialysate levels in the treated group were markedly elevated compared with control values: control, 233 ± 43 pg/ml; perindopril, 635 ± 53 pg/ml (p < 0.001). These results were confirmed by a complementary study in which dopamine content was measured in striatal extracts (3.5 ± 0.4 µg of dopamine/g of tissue for controls compared with 9.2 ± 2.4 µg of dopamine/g of tissue for the treated group; p < 0.05). In the rats that were dialyzed, angiotensin-converting enzyme levels in the striatum were decreased by 50% after perindopril treatment. Levels of dopamine D1 and D2 receptors and of preprotachykinin and tyrosine hydroxylase mRNAs were unchanged after angiotensin-converting enzyme inhibition. A small, but significant, increase was detected in striatal preproenkephalin mRNA levels in the angiotensin-converting enzyme inhibitor-treated group. These results indicate that peripherally administered angiotensin-converting enzyme inhibitors penetrate the blood-brain barrier when given chronically and modulate extracellular dopamine and striatal neuropeptide levels.