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Selective over expression of central ACE2 prevents baroreflex dysfunction in the chronic heart failure
Author(s) -
GAO LIE,
Farrar Rachael,
Wang Wei,
Lazartigues Eric D,
Zucker Irving H
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.610.2
Subject(s) - baroreflex , heart failure , medicine , phenylephrine , endocrinology , angiotensin converting enzyme 2 , blood pressure , renin–angiotensin system , angiotensin ii , heart rate , chemistry , disease , covid-19 , infectious disease (medical specialty)
Angiotensin‐converting enzyme 2 (ACE2) and Ang (1‐7) enhances baroreflex sensitivity (BRS). On the other hand Ang II depresses BRS and down regulates NOS expression, especially in the setting of chronic heart failure (CHF). Down regulation of brain NOS expression plays a role in the blunted BRS and sympatho‐excitation in the CHF state. We hypothesized that central over expression of ACE2 normalizes sympathetic outflow and BRS via up regulating NOS in this syndrome. Experiments were carried out in mice with selectively overexpressed human ACE2 in the brain (driven by the synapsin promoter; synhACE2) and wild type mice (WT), which were divided into sham (S) and CHF groups. Blood pressure, heart rate, and renal sympathetic nerve activity (RSNA) were recorded under anaesthesia. BRS was tested by iv injection of phenylephrine. We found that, (1) ACE2 and eNOS expressions were lower in WT‐CHF than WT‐S, but not different between synhACE2‐CHF and synhACE2‐S mice; (2) baseline RSNA was significantly lower in synhACE2‐CHF mice compared to WT‐CHF mice(RSNA: 47.4 ± 6.1 to 81.3 ± 7.6 % of Max; P < 0.05); (3) synhACE2‐CHF mice exhibited improved BRS compared with WT‐CHF mice (Maximum Slope: 3.4 ± 0.6 to 1.8 ± 0.8 %/mm Hg; P < 0.05). These results suggest that, selective over expression of ACE2 in the brain prevents impairment of BRS and sympatho‐excitation in the CHF state, probably via an up regulation of central NOS expression.