|
 |
|||||||||||||||||||
|
|||||||||||||||||||
|
|||||||||||||||||||
 |
 |
|
|
Section on Pharmacology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA
Address for correspondence: Hiromichi Ando, M.D., Ph.D., Section on Pharmacology, DIRP, NIMH, NIH, DHHS, 10 Center Drive, Bldg. 10, Room 2D-57, Bethesda, MD 20892, USA. Voice: 301-402-6859; fax: 301-402-0337. e-mail: Saavedrj{at}irp.nimh.nih.gov Ann. N.Y. Acad. Sci. 1018: 345-350 (2004).
The spontaneously hypertensive rats (SHR) are a genetically hypertensive strain with vulnerability to brain ischemia and stress. In SHR, the brain Angiotensin II (Ang II) system is chronically stimulated, resulting in brain artery remodeling and inflammation. Pretreatment with Ang II AT1 receptor antagonists protects from brain ischemia and prevents the hormonal and sympathoadrenal response to stress. In addition, the anti-inflammatory effects of AT1 receptor antagonists are partially responsible for preventing the development of stress-induced gastric ulcers. We asked whether AT1 receptor antagonists could exert anti-inflammatory effects in the brain vasculature as a mechanism for their protective effects against ischemia. As determined by immunohistochemistry, long-term inhibition of brain AT1 receptors by peripheral administration of the AT1 receptor antagonist candesartan (0.3 mg/kg/day for 28 days) normalized the pathologic remodeling, decreased expression of the intercellular adhesion molecule-1 and the number of associated macrophages, and normalized the endothelial nitric oxide synthase expression in cerebral vessels of SHR. The anti-inflammatory effects of AT1 receptor antagonists may be an important mechanism for protection against ischemia and could participate in the anti-stress properties of this class of compounds.
Key Words: Angiotensin II AT1 receptor • inflammation • brain microvessels • stress • eNOS • ICAM-1 • macrophages
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
