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Title: ACE inhibition reduces infarction in normotensive but not hypertensive rats: correlation with cortical ACE activity.
Austin Authors: Porritt, Michelle J;Chen, Michelle;Rewell, Sarah S J;Dean, Rachael G;Burrell, Louise M ;Howells, David William
Affiliation: Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: 21-Apr-2010
Publication information: Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism 2010; 30(8): 1520-6
Abstract: Angiotensin-converting enzyme (ACE) inhibition can reduce stroke risk by up to 43% in humans and reduce the associated disability, and hence understanding the mechanism of improvement is important. In animals and humans, these effects may be independent of the blood pressure-lowering effects of ACE inhibition. Normotensive (Wistar-Kyoto (WKY)) and hypertensive (spontaneously hypertensive rat (SHR)) animals were treated with the ACE inhibitors ramipril or lisinopril for 7 or 42 days before 2 hours of transient middle cerebral artery occlusion (MCAo). Blood pressure, serum ACE, and blood glucose levels were measured and stroke infarct volume was recorded 24 hours after stroke. Despite greater reductions in blood pressure, infarct size was not improved by ACE inhibition in hypertensive animals. Short-term ACE inhibition produced only a modest reduction in blood pressure, but WKY rats showed marked reductions in infarct volume. Long-term ACE inhibition had additional reductions in blood pressure; however, infarct volumes in WKY rats did not improve further but worsened. WKY rats differed from SHR in having marked cortical ACE activity that was highly sensitive to ACE inhibition. The beneficial effects of ACE inhibition on infarct volume in normotensive rats do not correlate with changes in blood pressure. However, WKY rats have ACE inhibitor-sensitive cortical ACE activity that is lacking in the SHR.
Gov't Doc #: 20407464
DOI: 10.1038/jcbfm.2010.57
Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Type: Journal Article
Subjects: Angiotensin-Converting Enzyme Inhibitors.therapeutic use
Cerebral Cortex.drug effects.enzymology
Hypertension.drug therapy.enzymology
Infarction, Middle Cerebral Artery.drug therapy.enzymology
Lisinopril.therapeutic use
Peptidyl-Dipeptidase A.metabolism
Ramipril.therapeutic use
Rats, Wistar
Appears in Collections:Journal articles

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