TY - CHAP
T1 - AT2R and Sympathetic Outflow
AU - Gao, Lie
AU - Zucker, Irving H.
N1 - Funding Information:
Some of the experiments described in this review were supported by grants PO-1 HL62222 (Dr. Irving H. Zucker) and RO-1 HL093028 (Dr. Lie Gao) from the National Institutes of Health. The authors thank Dr. Colin Sumners (University of Florida, the United States) for his generous donation of AT 2 R adenoviral vector. The AT 2 R knockout mice were kindly supplied by Dr. Thomas Walther (University College Cork, Ireland; University of Leipzig, Germany). The authors appreciate the critical support from Dr. Walther.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/4/22
Y1 - 2015/4/22
N2 - Angiotensin type 2 receptor (AT2R) protein content has been demonstrated in the sympathetic regulatory regions of the brain in mature rats and mice. In the rostral ventrolateral medulla of normal animals, the AT2R tonically suppresses sympathetic tone by increasing presympathetic neuronal potassium current and therefore reducing neuronal excitability and discharge. In the chronic heart failure (CHF) state and in neurogenic hypertension, central AT2R expression is significantly downregulated. This pathological alteration of AT2R signaling contributes to sympathetic hyperactivity, a major characteristic of these two diseases. Gene transfer-induced overexpression and pharmacologically evoked activation of central AT2Rs provide a potential therapeutic strategy in the CHF and hypertension states by promoting sympathetic inhibition.
AB - Angiotensin type 2 receptor (AT2R) protein content has been demonstrated in the sympathetic regulatory regions of the brain in mature rats and mice. In the rostral ventrolateral medulla of normal animals, the AT2R tonically suppresses sympathetic tone by increasing presympathetic neuronal potassium current and therefore reducing neuronal excitability and discharge. In the chronic heart failure (CHF) state and in neurogenic hypertension, central AT2R expression is significantly downregulated. This pathological alteration of AT2R signaling contributes to sympathetic hyperactivity, a major characteristic of these two diseases. Gene transfer-induced overexpression and pharmacologically evoked activation of central AT2Rs provide a potential therapeutic strategy in the CHF and hypertension states by promoting sympathetic inhibition.
KW - Angiotensin type 2 receptor
KW - Chronic heart failure
KW - Compound 21
KW - Neurogenic hypertension
KW - Neuronal -potassium channel
KW - Neuronal discharge
KW - Presympathetic neurons
KW - Renal sympathetic nerve activity
KW - Rostral ventrolateral medulla
KW - Sympathetic regulation
UR - http://www.scopus.com/inward/record.url?scp=84940044416&partnerID=8YFLogxK
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U2 - 10.1016/B978-0-12-801364-9.00015-8
DO - 10.1016/B978-0-12-801364-9.00015-8
M3 - Chapter
AN - SCOPUS:84940044416
SN - 9780128013649
SP - 109
EP - 118
BT - The Protective Arm of the Renin Angiotensin System (RAS)
PB - Elsevier Inc.
ER -