Abstract

The paraventricular nucleus of the hypothalamus (PVN) is an established center of cardiovascular control, receiving projections from other nuclei of the hypothalamus such as the dorsomedial hypothalamus and the suprachiasmatic nucleus. The PVN contains a population of “pre‐autonomic neurones” which project to the intermediolateralis of the spinal cord and increase sympathetic activity, blood pressure, and heart rate. These spinally projecting neurones express a number of membrane receptors including GABA and substance P NK1 receptors. Activation of NK1‐expressing neurones increases heart rate, blood pressure, and sympathetic activity. However, their role in the pattern of overall cardiovascular control remains unknown. In this work, we use specific saporin lesion of NK1‐expressing PVN rat neurones with SSP‐SAP and telemetrically measure resting heart rate and heart rate variability (HRV) parameters in response to mild psychological stress. The HRV parameter “low frequency/high frequency ratio” is often used as an indicator of sympathetic activity and is significantly increased with psychological stress in control rats (0.84 ± 0.14 to 2.02 ± 0.15; P < 0.001; n = 3). We find the stress‐induced increase in this parameter to be blunted in the SSP‐SAP‐lesioned rats (0.83 ± 0.09 to 0.93 ± 0.21; P > 0.05; n = 3). We also find a shift in daily variation of heart rate rhythm and conclude that NK1‐expressing PVN neurones are involved with coupling of the cardiovascular system to daily heart rate variation and the sympathetic response to psychological stress.

Highlights

  • A population of paraventricular nucleus (PVN) hypothalamic parvocellular neurones projects directly to sympathetic control “centres” of the medulla and spinal cord (Pyner and Coote 2000) and modulates heart rate (HR) and blood pressure (BP) (Coote 2007)

  • We report the effect of selective lesion of PVN neurokinin 1 (NK1)receptor-expressing neurones on heart rate and heart rate response to psychological stress in rats

  • To confirm the action of the substance P-saporin (SSP-SAP) lesion and the coordinates we have derived based on the stereotaxic rat atlas (Paxinos and Watson 1986) we used immunofluorescence of the NK1 receptor on the PVN

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Summary

Introduction

A population of paraventricular nucleus (PVN) hypothalamic parvocellular neurones projects directly to sympathetic control “centres” of the medulla and spinal cord (Pyner and Coote 2000) and modulates heart rate (HR) and blood pressure (BP) (Coote 2007). The activity of these neurones becomes elevated in heart failure as their tonic inhibitory GABA-ergic input becomes reduced (Pyner 2014). This pathway is of huge importance to cardiovascular medicine, there is no consensus as to its specific role in cardiovascular control. We report the effect of selective lesion of PVN neurokinin 1 (NK1)receptor-expressing neurones on heart rate and heart rate response to psychological stress in rats

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