Neuronal angiotensin-converting enzyme (ACE) gene expression is increased by converting enzyme inhibitors (CEI)

Abstract

Exposure to angiotensin-converting enzyme (ACE) inhibitors has been associated with increased ACE activity in vivo and in vitro. In the current study, we examined the effects of ACE inhibitors on ACE gene expression and activity in brain and primary neuronal cultures prepared from brains of neonatal spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) controls. ACE mRNA levels were increased in brain and neuronal cultures following ACE inhibitor exposure. A concomitant increase in ACE activity was evident in brain, but ACE activity was decreased in neuronal cultures following ACE inhibitor exposure. Since ACE has been localized to several cell types in the brain, including endothelial cells and glia, as well as neurons, the differences in ACE activity between whole brain and neuronal cultures following exposure to ACE inhibitors may be related to differential regulation of the ACE gene in these cell types. These findings and the observation that ACE mRNA levels are >20-fold higher in cultured neurons from neonatal SHR than in those from WKY support the conclusions that the activity of the brain renin angiotensin system is enhanced in SHR and that blockade of this system by chronic ACE inhibitor treatment contributes to the sustained antihypertensive effect of ACE inhibitors in this model.