TY - JOUR
T1 - A novel heart failure mice model of hypertensive heart disease by angiotensin II infusion, nephrectomy, and salt loading
AU - Tsukamoto, Yasumasa
AU - Mano, Toshiaki
AU - Sakata, Yasushi
AU - Ohtani, Tomohito
AU - Takeda, Yasuharu
AU - Tamaki, Shunsuke
AU - Omori, Yosuke
AU - Ikeya, Yukitoshi
AU - Saito, Yuki
AU - Ishii, Ryohei
AU - Higashimori, Mitsuru
AU - Kaneko, Makoto
AU - Miwa, Takeshi
AU - Yamamoto, Kazuhiro
AU - Komuro, Issei
PY - 2013/12/1
Y1 - 2013/12/1
N2 - 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.
AB - 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.
KW - Angiotensin II
KW - Heart failure
KW - Hypertensive heart disease
KW - Mouse model
KW - Renal dysfunction
KW - Salt loading
UR - http://www.scopus.com/inward/record.url?scp=84888872239&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00349.2013
DO - 10.1152/ajpheart.00349.2013
M3 - Article
C2 - 24043257
AN - SCOPUS:84888872239
SN - 0363-6135
VL - 305
SP - H1658-H1667
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 11
ER -