title: Cerebral microvascular inflammation in DOCA salt-induced hypertension: role of angiotensin II and mitochondrial superoxide.
abstract: Angiotensin II-mediated hypertension (HTN) is accompanied by a pro-inflammatory and pro-thrombotic state in the cerebral microvasculature. Whether comparable phenotypic changes are elicited in other models of HTN remains unclear. Using wild-type mice with deoxycorticosterone acetate (DOCA) salt-induced HTN and intravital microscopy, we observed significant increases in the adhesion of both leukocytes and platelets in cerebral venules, compared with uninephrectomized control mice, without an accompanying increase in blood-brain barrier permeability. The cell-cell interactions in hypertensive mice were more pronounced after ischemic stroke, but no difference in infarct size was detected. The blood cell recruitment was largely prevented in the following groups of DOCA salt mice: losartan (angiotensin II AT1 receptor blocker) treated, AT1 receptor knockout mice, tempol (a membrane-permeable oxygen radical scavenger) treated, and mito-TEMPO (a mitochondria-targeted antioxidant) treated. A similar pattern of protection was noted in mice subjected to ischemic stroke. The blunted cell recruitment responses were not accompanied by reductions in blood pressure (BP). These findings implicate mitochondria-derived oxygen radicals and angiotensin II in the cerebral inflammation associated with DOCA salt HTN and suggests that BP per se is not a critical determinant of the phenotypic changes that accompany HTN, even after ischemic stroke.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Rodrigues
authors.forename: Daniel Neil
authors.initials: DN
authors.lastname: Granger
mesh_terms: D000804:Angiotensin II / Q000276:immunology*; D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply* / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D003900:Desoxycorticosterone / Q000009:adverse effects*; D006973:Hypertension / Q000139:chemically induced* / Q000276:immunology; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000187:drug effects; D008901:Mineralocorticoids / Q000009:adverse effects*; D008928:Mitochondria / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology; D020521:Stroke / Q000276:immunology; D013481:Superoxides / Q000276:immunology*
chemical_list: D016207:Cytokines; D008901:Mineralocorticoids; D017382:Reactive Oxygen Species; D013481:Superoxides; D000804:Angiotensin II; D003900:Desoxycorticosterone