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Neuronal angiotensin-converting enzyme (ACE) gene expression is increased by converting enzyme inhibitors (CEI)
S J King1, S Oparil, K H Berecek
1Hypertension Program, Division of Cardiovascular Disease, Departments of Cell Biology, Medicine and Physiology, and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Molecular and Cellular Neurosciences
|November 17, 2009
Summary
Angiotensin-converting enzyme (ACE) inhibitors increase ACE gene expression in the brain. While ACE activity rises in the whole brain, it decreases in neuronal cultures, suggesting complex regulation contributing to ACE inhibitor antihypertensive effects.
Area of Science:
- Neuroscience
- Pharmacology
- Cardiovascular Research
Background:
- Angiotensin-converting enzyme (ACE) inhibitors are known to affect ACE activity.
- The brain renin-angiotensin system plays a role in blood pressure regulation.
Purpose of the Study:
- To investigate the effects of ACE inhibitors on ACE gene expression and activity in the brain.
- To compare these effects in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) controls.
Main Methods:
- Examined ACE mRNA levels and activity in brain tissue and primary neuronal cultures.
- Utilized neonatal SHR and WKY rats as experimental models.
Main Results:
- ACE inhibitor exposure increased ACE mRNA in both brain and neuronal cultures.
- Whole brain ACE activity increased, but neuronal culture ACE activity decreased post-treatment.
- Cultured neurons from neonatal SHR showed significantly higher ACE mRNA levels than WKY controls.
Conclusions:
- ACE inhibitor treatment enhances ACE gene expression in the brain.
- Differential regulation of ACE activity occurs in various brain cell types (neurons, glia, endothelial cells).
- Chronic ACE inhibitor treatment contributes to sustained antihypertensive effects in SHR by modulating the brain renin-angiotensin system.
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