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Central angiotensin‐converting enzyme 2 overexpression decreases blood pressure and enhances baroreflex function in mice with chronic heart failure
Author(s) -
Xiao Liang,
Gao Lie,
Lazartigues Eric,
Zucker Irving H
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.809.20
Subject(s) - baroreflex , angiotensin converting enzyme 2 , medicine , heart failure , endocrinology , angiotensin ii , renin–angiotensin system , blood pressure , ejection fraction , chemistry , angiotensin converting enzyme , cardiac function curve , heart rate , disease , covid-19 , infectious disease (medical specialty)
Central angiotensin‐converting enzyme 2 (ACE2) contributes to the regulation of cardiovascular function through modulating other components of the renin‐angiotensin system (RAS) in the brain. Since chronic heart failure (HF) is associated with sympathoexcitation, impaired baroreflex function and activation of the central RAS, we hypothesized that overexpression of ACE2 decreases blood pressure (BP) and improves baroreflex sensitivity in HF. Transgenic mice overexpressing human ACE2 selectively in the brain (Syn‐hACE2) and their wild type littermates (WT) were used, both of which developed HF (ejection fraction <45%, echocardiography) four weeks after coronary artery ligation. 24‐hour BP was monitored by radiotelemetry. Compared with WT HF group, Syn‐hACE2 HF mice exhibited lower mean BP, and ameliorated the spontaneous baroreflex sensitivity (SBRS, sequence method). These data indicate a beneficial role of central ACE2 overexpression during HF, and we speculate that ACE2 overexpression attenuates the augmented sympathetic outflow through decreasing angiotensin (Ang) II and/or increasing Ang 1–7 in the brain.WT Sham (n=5) Syn‐ACE2 Sham (n=5) WT HF (n=4) Syn‐ACE2 HF (n=4)Mean BP (mmHg) 113±3.2 113.7±5.0 109.2±4.7 88.9±4.7 # Heart Rate (bpm) 599.5±18.9 578.1.5±21.2 647.2±20.8 644.8±10.8 SBRS (ms/mmHg) 2.21±0.24 2.91±0.51 0.82±0.15 * 1.80±0.19 #* p<0.05 vs. WT sham;# p<0.05 vs. WT HF.