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Neuron‐targeted expression of ACE2 in the central nervous system prevents angiotensin‐II‐mediated hypertension
Author(s) -
FENG Yumei,
Xia Huijing,
Bindom Sharell M,
Lazartigues Eric
Publication year - 2008
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.22.1_supplement.741.1
Subject(s) - angiotensin converting enzyme 2 , baroreflex , endocrinology , medicine , renin–angiotensin system , angiotensin ii , neuron , transgene , genetically modified mouse , blood pressure , central nervous system , immunohistochemistry , chemistry , biology , neuroscience , heart rate , gene , biochemistry , disease , covid-19 , infectious disease (medical specialty)
We previously showed that Angiotensin Converting Enzyme type 2 (ACE2) is a member of the brain renin‐angiotensin system. To elucidate the physiological importance of central ACE2, we developed a new transgenic mouse model (Syn‐ACE2) with neuron‐targeted ACE2 overexpression in the brain. Using immunohistochemistry we observed ACE2 overexpression in brain nuclei involved in blood pressure (BP) regulation, such as the RVLM, SFO and NTS, suggesting a local role for ACE2. To test this hypothesis, Syn‐ACE2 mice and littermates (n=6/group) were infused with AngII (osmotic pump: 600 ng/kg.min) for 14 days. Baseline BP (telemetry: 112±3 vs. 114±4 mmHg) and baroreflex gain (sequence method: 1.8±0.2 vs. 1.5±0.2 msec/mmHg) were similar in Syn‐ACE2 and control mice, respectively while the LF/HF ratio (BP variability) was significantly lower in transgenic mice (10±2 vs. 19±2; P<0.01). AngII infusion resulted in hypertension in littermates (135±3 mmHg) while Syn‐ACE2 mice remained normotensive (101±5 mmHg; P<0.01). At this time, baroreflex gain (2.3±0.1 vs. 2.2±0.1 msec/mmHg) and LF/HF ratio (17±2 vs. 15±2) were not significantly different between Syn‐ACE2 and littermates, respectively. Our data show that ACE2 overexpression improves autonomic function in Syn‐ACE2 mice, thus protecting them from AngII‐mediated hypertension, and support a role for ACE2 in the central regulation of BP. (NIH NS052479 and P20RR018766)