title: A novel heart failure mice model of hypertensive heart disease by angiotensin II infusion, nephrectomy, and salt loading.
abstract: Although the mouse heart failure (HF) model of hypertensive heart disease (HHD) is useful to investigate the pathophysiology and new therapeutic targets for HHD, the model using simple experimental procedures and stable phenotypes has not been established. This study aimed to develop a novel mouse HF model of HHD by combining salt loading and uninephrectomy with ANG II infusion. Eight-week-old C57BL/6 male mice were treated with ANG II infusion (AT), ANG II infusion and uninephrectomy (AN), ANG II infusion and salt loading (AS), or ANG II infusion, uninephrectomy, and salt loading (ANS). Systolic blood pressure was significantly elevated and left ventricular (LV) hypertrophy was found in AT, AN, AS, and ANS mice, and there were no significant differences in those parameters between the four groups. At 6 wk after the procedures, only ANS mice showed significant decreases in LV fractional shortening and increases in lung weight with a high incidence. This phenotype was reproducible, and there were few perioperative or early deaths in the experimental procedures. Severe LV fibrosis was found in ANS mice. Oxidative stress was enhanced and small GTPase Rac1 activity was upregulated in the hearts of ANS mice. After the addition of salt loading and uninephrectomy to the ANG II infusion mouse model, cardiac function was significantly impaired, and mice developed HF. This might be a novel and useful mouse HF model to study the transition from compensated LV hypertrophy to HF in HHD.
authors.affiliation: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan;
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Tsukamoto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Mano
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sakata
authors.forename: Tomohito
authors.initials: T
authors.lastname: Ohtani
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Takeda
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tamaki
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Omori
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Ikeya
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saito
authors.forename: Ryohei
authors.initials: R
authors.lastname: Ishii
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Higashimori
authors.forename: Makoto
authors.initials: M
authors.lastname: Kaneko
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miwa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D000804:Angiotensin II; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000150:complications / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009392:Nephrectomy; D009479:Neuropeptides / Q000378:metabolism; D018384:Oxidative Stress; D011654:Pulmonary Edema / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D017673:Sodium Chloride, Dietary; D013997:Time Factors; D016277:Ventricular Function, Left; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D009479:Neuropeptides; C484602:Rac1 protein, mouse; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; D020830:rac1 GTP-Binding Protein
keywords: angiotensin II; heart failure; hypertensive heart disease; mouse model; renal dysfunction; salt loading