Brain-Selective Overexpression of Angiotensin-Converting Enzyme 2 Attenuates Sympathetic Nerve Activity and Enhances Baroreflex Function in Chronic Heart Failure

Content Provider	Scilit
Author	Xiao, Liang Gao, Lie Lazartigues, Eric Zucker, Irving H.
Copyright Year	2011
Description	Journal: Hypertension Angiotensin-converting enzyme 2 (ACE2) has been suggested to be involved in the central regulation of autonomic function. During chronic heart failure (CHF), elevated central angiotensin II signaling contributes to the sustained increase of sympathetic outflow. This is accompanied by a downregulation of ACE2 in the brain. We hypothesized that central overexpression of ACE2 decreases sympathetic outflow and enhances baroreflex function in CHF. Transgenic mice overexpressing human ACE2 selectively in the brain (SYN-hACE2 [SA]) and wild-type littermates (WT) were used. CHF was induced by permanent coronary artery ligation. Four weeks after coronary artery ligation, both WT and SA mice exhibited a significant decrease in left ventricular ejection fraction (<40%). A slight decrease in mean arterial pressure was found only in SA mice. Compared with WT mice with CHF, brain-selective ACE2 overexpression attenuated left ventricular end-diastolic pressure; decreased urinary norepinephrine excretion; baseline renal sympathetic nerve activity (WT CHF: 71.6±7.6% max versus SA CHF: 49.3±6.1% max); and enhanced baroreflex sensitivity (maximum slope: WT sham: 1.61±0.16%/mm Hg versus SA CHF: 1.51±0.17%/mm Hg). Chronic subcutaneous blockade of mas receptor increased renal sympathetic nerve activity in SA mice with CHF (A779: 67.3±5.8% versus vehicle: 46.4±3.6% of max). An upregulation in angiotensin II type 1 receptor expression was detected in medullary nuclei in WT CHF mice, which was significantly attenuated in SA mice with CHF. These data suggest that central ACE2 overexpression exerts a potential protective effect in CHF through attenuating sympathetic outflow. The mechanism for this effect involves angiotensin (1-7) mas signaling, as well as a decrease in angiotensin II type 1 receptor signaling in the medulla.
Related Links	https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.111.176636 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224814/pdf https://www.ahajournals.org/doi/reader/10.1161/HYPERTENSIONAHA.111.176636
Ending Page	1065
Page Count	9
Starting Page	1057
ISSN	0194911X
e-ISSN	15244563
DOI	10.1161/hypertensionaha.111.176636
Journal	Hypertension
Issue Number	6
Volume Number	58
Language	English
Publisher	Ovid Technologies (Wolters Kluwer Health)
Publisher Date	2011-12-01
Access Restriction	Open
Subject Keyword	Journal: Hypertension Peripheral Vascular Disease Heart Failure Angiotensin Ii Angiotensin-converting Enzyme 2 Angiotensin I (1-7) Autonomic Function
Content Type	Text
Resource Type	Article
Subject	Internal Medicine