Restraining influence of A2 neurons in chronic control of arterial pressure in spontaneously hypertensive rats

Abstract

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_ir2.1. The dorsal vagal complex containing the A2 cell group was microinjected with the PRSx8-hK_ir2.1 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; ppConclusions 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.