Journal
CARDIOVASCULAR RESEARCH
Volume 76, Issue 1, Pages 184-193Publisher
OXFORD UNIV PRESS
DOI: 10.1016/j.cardiores.2007.06.018
Keywords
nucleus tractus solitarii; hypertension; norepinephrine; lentivirus
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Objectives: The role of A2 noradrenergic neurons in regulating cardiovascular homeostasis chronically is poorly understood. We aimed to genetically target A2 neurons and induce expression of a potassium channel to reduce their electrical excitability and study how this impacts on long-term blood pressure control. Methods: We used a lentiviral vector with PRSx8 promoter for targeting noradrenergic neurons to express a human inwardly rectifying potassium channel, hK(ir)2.1. The dorsal vagal complex containing the A2 cell group was microinjected with the PRSx8-hK(ir)2.1 lentivirus in both normotensive Wistar rats and spontaneously hypertensive rats fitted with radio telemetry devices. Results: In Wistar rats expression of hKir2.1 increased lability of arterial pressure between 7 to 21 days post-injection with mean arterial pressure not increasing significantly until day 21 (+ 11 +/- 1 mmHg; p<0.001; dark phase). Urine output and water intake were both decreased. In contrast, in spontaneously hypertensive rats not only the lability of arterial pressure but also the mean arterial pressure increased by day 7 and persisted during the 21 day recording period (+ 13 +/- 1 mmHg; p<0.001 at day 21). In contrast to Wistar rats, body fluid homeostasis was un-affected in hypertensive rats. Neither cardiac baroreceptor reflex gain nor heart rate variability changed in either rat strain. Plasma osmolality levels were also unaffected. Conclusions: Our data indicate a role for A2 neurons in the chronic regulation of arterial pressure independent of the cardiac baroreceptor reflex. The activity of A2 neurons may constitute an essential part of the central circuitry underpinning chronic regulation of arterial pressure in both, normo- and hypertensive rats. (C) 2007 European Society of Cardiology. Published by Elsevier B.V All rights reserved.
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