Angiotensin 1A receptors transfected into caudal ventrolateral medulla inhibit baroreflex gain and stress responses

Palma-Rigo, Kesia, Bassi, Jaspreet K., Nguyen-Huu, Thu-Phuc, Jackson, Kristy L., Davern, Pamela J., Chen, Daian, Elghozi, Jean-Luc, Thomas, Walter G., Allen, Andrew M. and Head, Geoffrey A. (2012) Angiotensin 1A receptors transfected into caudal ventrolateral medulla inhibit baroreflex gain and stress responses. Cardiovascular Research, 96 2: 330-339. doi:10.1093/cvr/cvs252

Author Palma-Rigo, Kesia
Bassi, Jaspreet K.
Nguyen-Huu, Thu-Phuc
Jackson, Kristy L.
Davern, Pamela J.
Chen, Daian
Elghozi, Jean-Luc
Thomas, Walter G.
Allen, Andrew M.
Head, Geoffrey A.
Title Angiotensin 1A receptors transfected into caudal ventrolateral medulla inhibit baroreflex gain and stress responses
Journal name Cardiovascular Research   Check publisher's open access policy
ISSN 0008-6363
Publication date 2012-11
Sub-type Article (original research)
DOI 10.1093/cvr/cvs252
Volume 96
Issue 2
Start page 330
End page 339
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2013
Language eng
Formatted abstract
Aims: The caudal ventrolateral medulla (CVLM) is important for autonomic regulation and is rich in angiotensin II type 1A receptors (AT 1AR). To determine their function, we examined whether the expression of AT 1AR in the CVLM of mice lacking AT 1AR (AT 1A -/-) alters baroreflex sensitivity and cardiovascular responses to stress.

Methods and results: Bilateral microinjections into the CVLM of AT 1A -/- mice of lentivirus with the phox-2 selective promoter (PRSx8) were made to express either AT 1AR (Lv-PRSx8-AT 1A) or green fluorescent protein (Lv-PRSx8-GFP) as a control. Radiotelemetry was used to record mean arterial pressure (MAP), heart rate (HR), and locomotor activity. Following injection of Lv-PRSx8-GFP, robust neuronal expression of GFP was observed with ∼60 of the GFP-positive cells also expressing the catecholamine-synthetic enzyme tyrosine hydroxylase. After 5 weeks, there were no differences in MAP or HR between groups, but the Lv-PRSx8-AT 1A-injected mice showed reduced baroreflex sensitivity (-25, P 0.003) and attenuated pressor responses to cage-switch and restraint stress compared with the Lv-PRSx8-GFP-injected mice. Reduced MAP mid-frequency power during cage-switch stress reflected attenuated sympathetic activation (Pgroup × stress 0.04). Fos-immunohistochemistry indicated greater activation of forebrain and hypothalamic neurons in the Lv-PRSx8-AT 1A mice compared with the control.

Conclusion: The expression of AT 1AR in CVLM neurons, including A1 neurons, while having little influence on the basal blood pressure or HR, may play a tonic role in inhibiting cardiac vagal baroreflex sensitivity. However, they strongly facilitate the forebrain response to aversive stress, yet reduce the pressor response presumably through greater sympatho-inhibition. These findings outline novel and specific roles for angiotensin II in the CVLM in autonomic regulation.
Keyword Angiotensin type 1A receptor
Caudal ventrolateral medulla
Cardiovascular stress response
Baroreflex gain
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Online publish-ahead-of-print: 6 August 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Biomedical Sciences Publications
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