Differing Patterns of Ionotropic Glutamate Receptor Subunit Gene Expression in Paraventricular Hypothalamic Nucleus...

Introduction: The increased susceptibility to hypertension at menopause is characterized by alterations in brain circuits that regulate cardiovascular homeostasis; however, the mechanisms underlying this association are not well understood. Recent evidence using an accelerated ovarian failure (AOF) model of menopause demonstrates that hypertension is critically dependent on ionotropic glutamate receptor signaling in the hypothalamic paraventricular nucleus (PVN), a brain area critical for blood pressure regulation. There are various glutamate receptors (i.e., NMDA, AMPA) and functionally diverse PVN subregions (i.e., endocrine, autonomic), yet regional gene expression patterns of specific receptors during hypertension in AOF mice is lacking.

In situ hybridization was used to map gene expression of glutamate receptors in functionally distinct PVN subregions. Female mice were infused with slow-pressor angiotensin II (AngII) at a late stage of AOF comparable to postmenopause and were compared to age-matched male mice.

Hypertension affected the expression of AMPA or NMDA receptor genes exclusively in males and only in mediocaudal PVN subregions that are known to project to brainstem and spinal regions implicated in autonomic processes (Gria1 and Grin2a, respectively) or the anterior pituitary region (Gria2).

These findings demonstrate that altered expression of key ionotropic glutamate receptor genes is limited to regions critically involved in modulating sympathetic and parasympathetic activity as well as neuroendocrine processes in males only.