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ACE2 expression in the central nervous system reduces angiotensin‐II‐mediated hypertension and cardiac hypertrophy in transgenic mice.
Author(s) -
Feng Yumei,
McIlwain Elizabeth,
Varner Kurt,
Lazartigues Eric
Publication year - 2009
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.23.1_supplement.802.1
Subject(s) - medicine , ventricle , endocrinology , muscle hypertrophy , ejection fraction , renin–angiotensin system , angiotensin ii , transgene , angiotensin converting enzyme 2 , cardiac function curve , genetically modified mouse , cardiac hypertrophy , biology , heart failure , receptor , blood pressure , biochemistry , disease , covid-19 , infectious disease (medical specialty) , gene
Angiotensin converting enzyme 2 (ACE2) is an important member of the renin angiotensin system, recently identified in the central nervous system. We previously reported that central ACE2 reduces the development of hypertension induced by chronic Ang‐II infusion in transgenic mice (syn‐hACE2) with human ACE2 targeted selectively to neurons. To study the physiological consequences of central ACE2 over‐expression on cardiac function, syn‐hACE2 and control mice (n=8/group) were infused with Ang‐II (600 ng/kg.min sc) for 14 days and cardiac function assessed by echocardiography. Baseline BP (telemetry: 112 ±3 vs. 114 ±4 mmHg), ejection fraction (EF: 45 ±3 vs. 44 ±4%), fractional shortening (FS: 23 ±2 vs. 22 ±2) and left ventricle mass/tibia length (7.9 ±0.4 vs. 7.7 ±0.2) were similar between the two groups ( P >0.05). After 2‐week infusion, BP was elevated in controls (135 ±3 mmHg; P <0.01) but not in syn‐hACE2 (101 ±5 mmHg). Although EF and FS were not altered, Ang‐II infusion induced hypertrophy (LV mass/tibia length: 9.1 ±0.3 2PW/LVD: 0.4 ±0.02; P <0.05) in controls. However, in syn‐hACE2 mice, these parameters were significantly reduced (8.2 ±0.2 and 0.3 ±0.01, respectively; P <0.05). These data suggest that ACE2 over‐expression in the brain reduced Ang‐II‐mediated hypertension and protected syn‐hACE2 transgenic mice from sympathetic drive‐mediated cardiac hypertrophy. (AHA 0825459E, NIH RR018766 and HL093178 )