Copyright © 2007, European Society of Cardiology
Restraining influence of A2 neurons in chronic control of arterial pressure in spontaneously hypertensive rats
aDepartment of Physiology, Bristol Heart Institute, School of Medical Sciences, University Walk, University of Bristol, Bristol, BS8 1TD, UK
bDepartment of Pharmacology, Bristol Heart Institute, School of Medical Sciences, University Walk, University of Bristol, Bristol, BS8 1TD, UK
*Corresponding authors. Paton, is to be contacted at Department of Physiology, Bristol Heart Institute, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, UK. Tel.:+44 117 928 7818; fax:+44 117 928 8923. Teschemacher, Department of Pharmacology, Bristol Heart Institute, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, UK. Tel.: +44 117 928 8324; fax: +44 117 925 0168. Julian.F.R.Paton{at}Bristol.ac.uk
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, hKir2.1. The dorsal vagal complex containing the A2 cell group was microinjected with the PRSx8-hKir2.1 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.
KEYWORDS Nucleus tractus solitarii; Hypertension; Norepinephrine; Lentivirus
1 Currently at the Spinal Cord ... Brain Injury Research Center (SCoBIRC), University of Kentucky, Lexington, Kentucky, 40536-0509, USA.
2 AGT and JFRP are equal last authors.
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