Altered NMDA and GABA-A Receptor Subunit Expression in the Hypothalamic Paraventricular Nucleus of Hypertensive and Pregnant Rats

Abstract

Hypertension and pregnancy are both accompanied by increases in sympathetic nerve activity. This has been attributed in part, to changes in the neurochemistry of the hypothalamic paraventricular nucleus (PVN).

In hypertension, physiological studies have revealed that decreases in GABAergic inhibition and increases in glutamatergic excitation within the PVN contribute to this sympathoexcitation. In late-term pregnancy however, the sympathoexcitation appears to be mediated by decreases in GABAergic inhibition, with no glutamatergic contribution.

This study aimed to examine the molecular characteristics of the GABAA and NMDA receptor to ascertain whether changes in their subunit expression in the PVN could contribute to the sympathoexcitation observed in these physiological states.

Whole PVN micropunches subjected to quantitative immunoblotting were combined with semi-quantitative analysis of immunohistochemistry to ascertain which subunits were altered, and whether the alteration was confined to specific parvocellular subnuclei of the PVN.

The results of this study show that both hypertension and pregnancy are accompanied by significant decreases in both the α1 and α5 subunit of the GABAA receptor in the PVN. Furthermore, hypertension is also accompanied by a significant increase in the expression of the GluN2A subunit of the NMDA receptor, which was associated with increases in the number of GluN2A-immunoreactive neurones in specific parvocellular subnuclei of the PVN. Conversely, pregnancy was associated with a significant increase in GluN2B subunit expression which was not associated with changes in cell immunoreactivity in any parvocellular subnuclei.

The results from this study suggest that decreases in α1 and α5 subunits of the GABAA receptor may be important in mediating the sympathoexcitation observed in both of these physiological states, with the greater level of sympathoexcitation observed in hypertension possibly attributed to increases in GluN2A-mediated NMDA receptor expression.