Angiotensin II AT1 receptor blockade decreases brain artery inflammation in a stress-prone rat strain.
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 AT(1) receptor antagonists protects from brain ischemia and prevents the hormonal and sympathoadrenal response to stress. In addition, the anti-inflammatory effects of AT(1) receptor antagonists are partially responsible for preventing the development of stress-induced gastric ulcers. We asked whether AT(1) 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 AT(1) receptors by peripheral administration of the AT(1) 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 AT(1) receptor antagonists may be an important mechanism for protection against ischemia and could participate in the anti-stress properties of this class of compounds.
Ando
Hiromichi
H
Section on Pharmacology, DIRP, NIMH, NIH, DHHS, 10 Center Drive, Bldg. 10, Room 2D-57, Bethesda, MD 20892, USA.
Jezova
Miroslava
M
Zhou
Jin
J
Saavedra
Juan M
JM
D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001167:Arteritis / Q000378:metabolism* / Q000503:physiopathology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001921:Brain / Q000098:blood supply*; D002448:Cell Adhesion; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D018799:Intercellular Adhesion Molecule-1; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C081643:candesartan