Abstract

A characteristic of both hypertension and pregnancy is increased sympathetic nerve activity. The level of sympathetic activation is determined, in part, by a tonic GABAergic inhibition arising from the hypothalamic paraventricular nucleus (PVN). In hypertension, decreases in GABAergic inhibition and increases in glutamatergic excitation within the PVN contribute to this sympatho-excitation. In late-term pregnancy however, the sympatho-excitation appears to be mediated by decreases in GABAergic inhibition only. This study examined whether changes in subunit expression for GABAA receptors in the PVN could provide a molecular basis for the sympatho-excitation characteristic of hypertension and pregnancy. Hypertension and pregnancy were accompanied by significant decrease in the GABAA receptor α5 subunit in the PVN. We suggest that decreases in the α5 subunit of the GABAA receptor may be important in mediating the sympatho-excitation observed in both hypertension and pregnancy.

Highlights

  • The hypothalamic paraventricular nucleus (PVN) is a critical site for central integration of sympathetic outflow to the cardiovascular system [27]

  • Female spontaneously hypertensive rat (SHR) weighed 178 ± 2 g (n = 10) and pregnant Wistar group had a mean weight of 299 ± 7 g (n = 11)

  • The foetus mean weight was 2.16 ± 0.15 g placing them between gestation dates 19–20 [30]

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Summary

Introduction

The hypothalamic paraventricular nucleus (PVN) is a critical site for central integration of sympathetic outflow to the cardiovascular system [27]. Presympathetic PVN neurons have consistently been identified as making a significant contribution to the sympatho-excitation evident in (patho) physiological conditions [3,7,15]. The PVN contains both GABA and NMDA receptors and the normal tonic inhibition of vasomotor sympathetic nerve activity is dependent upon activation of GABAA with suppression of NMDA receptor activity [18]. GABAergic inhibition within the PVN can be phasic (synapticallymediated) or tonic (extrasynaptic) and these actions are mediated by receptors with physiological and pharmacologically distinct properties as well as subcellular localization. The SON and PVN are two anatomically distinct nuclei, their similar neurochemistry and cellular make up suggests that the control of tonic inhibition could be controlled in a similar manner

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