Expression of angiotensin type 1A receptors in C1 neurons restores the sympathoexcitation to angiotensin in the rostral ventrolateral medulla of angiotensin type 1A knockout mice

Chen, DA, Bassi, JK, Walther, T, Thomas, WG and Allen, AM (2010) Expression of angiotensin type 1A receptors in C1 neurons restores the sympathoexcitation to angiotensin in the rostral ventrolateral medulla of angiotensin type 1A knockout mice. Hypertension, 56 1: 143-150. doi:10.1161/HYPERTENSIONAHA.110.151704


Author Chen, DA
Bassi, JK
Walther, T
Thomas, WG
Allen, AM
Title Expression of angiotensin type 1A receptors in C1 neurons restores the sympathoexcitation to angiotensin in the rostral ventrolateral medulla of angiotensin type 1A knockout mice
Journal name Hypertension   Check publisher's open access policy
ISSN 0194-911X
1524-4563
Publication date 2010-07
Sub-type Article (original research)
DOI 10.1161/HYPERTENSIONAHA.110.151704
Volume 56
Issue 1
Start page 143
End page 150
Total pages 8
Place of publication Lippincott Williams & Wilkins
Publisher Philadelphia, PA, United States
Collection year 2011
Language eng
Formatted abstract
In adult mice we determined whether expression of angiotensin II (Ang II) type 1A receptors (AT1ARs) in C1 neurons mediates the excitation of the rostral ventrolateral medulla (RVLM) by Ang II. Blood pressure, heart rate, and sympathetic nerve activity were measured in anesthetized, artificially ventilated wild-type (n=15) and AT1AR knockout (AT1A-/-; n=9) mice. Microinjection of Ang II (50 nL of 0.1 to 1.0 mmol/L) into the RVLM induced a dose-related, sympathetically mediated pressor response (maximum of 17±2 mm Hg) in wild-type mice. These microinjections had no effect in AT1A-/- mice. Endogenous AT1Rs occur on catecholaminergic C1 neurons in the RVLM. We induced AT1A-/-R or green fluorescent protein expression in C1 neurons of AT1A-/- mice through bilateral microinjection of replication-deficient lentiviruses, with transgene expression under the control of a phox2 transcription factor binding promoter (PRSx8) (Lv-PRSx8-AT1A, n=10, and Lv-PRSx8-GFP, n=5). Transgene expression was observed in a significant proportion of RVLM C1 neurons. In anesthetized Lv-PRSx8-AT1A injected mice, unilateral RVLM microinjection of Ang II (50 nL of 1 mmol/L) increased blood pressure (17±4 mm Hg) and sympathetic nerve activity (155±32%). No response to Ang II occurred in Lv-PRSx8-GFP microinjected mice. These results show that Ang II-mediated excitation of RVLM neurons in adult mice depends on the AT1AR with little or no effect of type 1B or 2 receptors. Expression of the AT1AR predominantly in C1 catecholamine neurons restores the response to Ang II in the AT1A-/- mouse and demonstrates that these neurons are sympathoexcitatory in the mouse.
© 2010 American Heart Association, Inc.
Keyword Sympathetic
Blood pressure
RVLM
Angiotensin II
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Biomedical Sciences Publications
 
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Created: Sun, 04 Jul 2010, 00:04:43 EST