Premium
Mas receptor in the RVLM mediates sympatho‐inhibitory effect in mice with ACE2 overexpression during heart failure
Author(s) -
Xiao Liang,
Zucker Irving H
Publication year - 2012
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.26.1_supplement.lb797
Subject(s) - rostral ventrolateral medulla , medicine , microinjection , endocrinology , heart failure , receptor , cardiac function curve , heart rate , downregulation and upregulation , angiotensin ii , inhibitory postsynaptic potential , sympathetic nervous system , blood pressure , chemistry , biochemistry , gene
Elevated central Ang II signaling contributes to the sustained increase of sympathetic outflow during chronic heart failure (CHF). This is associated with downregulation of central angiotensin‐converting enzyme 2 (ACE2). We have previously shown that sympathetic outflow was attenuated in mice with neuron‐selective ACE2 overexpression (SYN‐hACE2, SA) during CHF. However, it is not clear whether this effect is due to Ang‐(1‐7) and mas receptor signaling in the pre‐sympathetic neurons in these mice. We hypothesized that knock‐down of the mas receptor in the RVLM increases sympathetic drive in SA mice during CHF. Five weeks after coronary artery ligation, mean arterial pressure (MAP) and heart rate (HR) were recorded with telemetry for 3 days. Lentivirus encoding MAS1 shRNA (mas KD) or scrambled shRNA (scrb) were microinjected into the RVLM bilaterally, and MAP and HR were recorded after 7 days of recovery. Although a decrease in MAP and increase in HR were observed as cardiac function deteriorated, mas KD had no effect in wild type mice. In SA mice, HR was maintained after control microinjection (590±4 bpm vs. 588±6 bpm), however mas receptor KD increased HR (595±1 bpm vs. 618±5 bpm, p<0.05). MAP was decreased similarly in two groups. These data suggest that the cardiac sympatho‐inhibitory effect of central ACE2 overexpression is mediated through mas receptor in the RVLM.