title: Cognitive impairment in heart failure: A protective role for angiotensin-(1-7).
abstract: Patients with congestive heart failure (CHF) have increased hospital readmission rates and mortality if they are concomitantly diagnosed with cognitive decline and memory loss. Accordingly, we developed a preclinical model of CHF-induced cognitive impairment with the goal of developing novel protective therapies against CHF related cognitive decline. CHF was induced by ligation of the left coronary artery to instigate a myocardial infarction (MI). By 4- and 8-weeks post-MI, CHF mice had approximately a 50% and 70% decline in ejection fraction as measured by echocardiography. At both 4- and 8-weeks post-MI, spatial memory performance in CHF mice as tested using the Morris water task was significantly impaired as compared with sham. In addition, CHF mice had significantly worse performance on object recognition when compared with shams as measured by discrimination ratios during the novel object recognition NOR task. At 8-weeks post-MI, a subgroup of CHF mice were given Angiotensin (Ang)-(1-7) (50mcg/kg/hr) subcutaneously for 4 weeks. Following 3 weeks treatment with systemic Ang-(1-7), the CHF mice NOR discrimination ratios were similar to shams and significantly better than the performance of CHF mice treated with saline. Ang-(1-7) also improved spatial memory in CHF mice as compared with shams. Ang-(1-7) had no effect on cardiac function. Inflammatory biomarker studies from plasma revealed a pattern of neuroprotection that may underlie the observed improvements in cognition. These results demonstrate a preclinical mouse model of CHF that exhibits both spatial memory and object recognition dysfunction. Furthermore, this CHF-induced cognitive impairment is attenuated by treatment with systemic Ang-(1-7). (PsycINFO Database Record
authors.affiliation: Department of Physiology, University of Arizona.
authors.forename: Meredith
authors.initials: M
authors.lastname: Hay
authors.affiliation: Department of Pharmacology, University of Arizona.
authors.forename: Todd W
authors.initials: TW
authors.lastname: Vanderah
authors.affiliation: Department of Physiology, University of Arizona.
authors.forename: Farmin
authors.initials: F
authors.lastname: Samareh-Jahani
authors.affiliation: Department of Physiology, University of Arizona.
authors.forename: Eleni
authors.initials: E
authors.lastname: Constantopoulos
authors.affiliation: Evelyn F. McKnight Brain Institute, University of Arizona.
authors.forename: Ajay R
authors.initials: AR
authors.lastname: Uprety
authors.affiliation: Evelyn F. McKnight Brain Institute, University of Arizona.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Barnes
authors.affiliation: Department of Physiology and Sarver Heart Center, University of Arizona.
authors.forename: John
authors.initials: J
authors.lastname: Konhilas
mesh_terms: D000803:Angiotensin I / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D060825:Cognitive Dysfunction / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000150:complications* / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000627:therapeutic use; D020257:Ventricular Remodeling / Q000187:drug effects; D014792:Visual Acuity / Q000187:drug effects
chemical_list: D010446:Peptide Fragments; D000803:Angiotensin I; C118790:angiotensin I (1-7)