title: Chronic perfusion of angiotensin II causes cognitive dysfunctions and anxiety in mice.
abstract: High blood pressure is a major risk factor in the onset of cerebrovascular diseases and cognitive impairment. However, mechanisms by which these occur remain unclear and treatments are, therefore, ineffective to prevent cognitive decline related to cardiovascular diseases. Angiotensin II is a peptide involved in the onset and maintenance of hypertension and its effect on cognition was studied acutely but never chronically. Hence, the aim of this study is to evaluate whether chronic hypertensive levels of angiotensin II infusion alter cognitive functions in C57BL6 mice. In this study we used subcutaneous mini-pumps containing a concentration of angiotensin II (1900 ng/kg/min) that induces malignant hypertension or a saline solution for 14 and 21 days. Blood pressure was carefully monitored by a non-invasive tail-cuff method every week throughout the experiment. Spatial memory was assessed using the Morris water maze test and anxiety was measured by the elevated plus maze and the open field tests. The results indicate learning and spatial memory deficit as well as an anxious behavior induced by angiotensin II, in comparison to the vehicle group, starting at the 3rd week of perfusion. The motricity and visual acuity were equivalent in angiotensin II perfused mice compared to their respective control. These results suggest a strong relationship between angiotensin II and the development of cognitive dysfunctions and anxiety along with sustained high blood pressure.
authors.affiliation: Department of Pharmacology, Université de Montréal, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Duchemin
authors.forename: E
authors.initials: E
authors.lastname: Belanger
authors.forename: R
authors.initials: R
authors.lastname: Wu
authors.forename: G
authors.initials: G
authors.lastname: Ferland
authors.forename: H
authors.initials: H
authors.lastname: Girouard
mesh_terms: D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001794:Blood Pressure / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000633:toxicity*
chemical_list: D014662:Vasoconstrictor Agents; D000804:Angiotensin II