Protection Against Ischemia and Improvement of Cerebral Blood Flow in Genetically Hypertensive Rats by Chronic Pretreatment With an Angiotensin II AT 1 Antagonist
- 1 September 2002
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Stroke
- Vol. 33 (9), 2297-2303
- https://doi.org/10.1161/01.str.0000027274.03779.f3
Abstract
Background and Purpose— Pretreatment with angiotensin II AT 1 receptor antagonists protects against cerebral ischemia. We studied whether modulation of cerebral blood flow (CBF) and morphometric changes in brain arteries participated in this protective mechanism. Methods— We pretreated adult spontaneously hypertensive rats with equally antihypertensive doses of candesartan (0.1 or 0.3 mg/kg per day), nicardipine (0.1 mg/kg per day), or captopril (3.0 mg/kg per day) for 3 or 28 days via subcutaneous osmotic minipumps followed by permanent left middle cerebral artery (MCA) occlusion distal to the origin of the lenticulostriate arteries. We measured CBF by autoradiography with 4-iodo-[ N -methyl- 14 C]antipyrine 3 hours after operation and the areas of infarct and tissue swelling 24 hours after operation. Morphometric changes in the MCA were studied after antihypertensive treatment. Results— Twenty-eight days of candesartan pretreatment decreased the infarct area by 31%; reduced the CBF decrease at the peripheral area of ischemia and the cortical volume of severe ischemic lesion, where CBF was Conclusions— Angiotensin II system inhibition protects against neuronal injury more effectively than calcium channel blockade. Protection after AT 1 receptor blockade is not directly correlated with blood pressure reduction but with normalization of MCA media thickness, leading to increased arterial compliance and reduced CBF decrease during ischemia at the periphery of the lesion.Keywords
This publication has 14 references indexed in Scilit:
- Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilationJCI Insight, 1999
- Myocardial blood flow in awake dogs with chronic tricuspid regurgitationBasic Research in Cardiology, 1998
- Angiotensin II AT, receptor mediated contraction of the perfused rat cerebral arteryNeuroReport, 1994
- Effect of antihypertensive treatment on focal cerebral infarction.Hypertension, 1992
- The CBF Threshold and Dynamics for Focal Cerebral Infarction in Spontaneously Hypertensive RatsJournal of Cerebral Blood Flow & Metabolism, 1992
- Cerebrovascular effects of angiotensin converting enzyme inhibition involve large artery dilatation in rats.Stroke, 1991
- Angiotensin II causes vascular hypertrophy in part by a non-pressor mechanism.Hypertension, 1991
- A Semiautomated Method for Measuring Brain Infarct VolumeJournal of Cerebral Blood Flow & Metabolism, 1990
- Focal Cerebral Ischaemia in the Rat: 1. Description of Technique and Early Neuropathological Consequences following Middle Cerebral Artery OcclusionJournal of Cerebral Blood Flow & Metabolism, 1981
- Effects of angiotensin II on cerebral blood vesselsActa Physiologica Scandinavica, 1979