Angiotensin II AT 1 Receptor Blockade Reverses Pathological Hypertrophy and Inflammation in Brain Microvessels of Spontaneously Hypertensive Rats

Abstract
Background and Purpose— The spontaneously hypertensive rat (SHR) is vulnerable to brain ischemia and stress and exhibits a chronically stimulated brain angiotensin II system, cerebrovascular hypertrophy, and inflammation. Pretreatment with angiotensin II type 1 (AT1) receptor antagonists protects from brain ischemia and from stress and prevents the development of stress-induced gastric ulcers in part by reducing inflammation in the gastric mucosa. We studied whether AT1 receptor antagonists could exert antiinflammatory effects in the brain vasculature as a mechanism for their protective effects against ischemia. Methods— Ten-week-old SHR and normotensive Wistar-Kyoto male rats received the AT1 receptor antagonist candesartan (0.3 mg/kg per day) or vehicle for 28 days via osmotic minipumps. We studied AT1 receptors, intercellular adhesion molecule-1 (ICAM-1), endothelial nitric oxide synthase (eNOS), and number of macrophages by immunohistochemistry and Western blots. Results— We found increased endothelia...

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