Neurogenic hypertension (NH) is strictly linked to changes in the neurotransmission/neuromodulation within the specifics nuclei of the hypothalamic-brainstem circuitry that control the cardiovascular reflex and sympathetic activity. Among these nuclei are the paraventricular nucleus of the hypothalamus (PVN) that controls the autonomic and neuroendocrine function, with direct inputs to premotor sympathoexcitatory neurons in the rostroventrolateral medulla (RVLM) and/or to sympathetic preganglionic neurons of the intermediolateral cell column (IML) of the spinal cord. Several studies have shown that PVN is composed by a complex neuronal network of excitatory and inhibitory neurotransmitters with inputs to different areas of central nervous system involved in the control of the autonomic function and, consequently, the blood pressure level. Moreover, PVN neurons that project to RVLM have a significant expression of purinergic receptors that could be close correlated to the sympathetic overactivity observed in hypertension stage. Based on these findings our aim in the present project is to evaluate the role of purinergic receptors in NH at the PVN level by controlling of the sympathetic outflow in spontaneous hypertensive rats and normotensive rats. For this, we will be using nanoinjection of purinergic receptors agonists and/or antagonists in the PVN, simultaneously to sympathetic nerve recordings. Furthermore, we will be evaluating the co-transmission between purinergic and adrenergic pathways, as well as the interaction of neuron and glia of this nucleus on sympathetic outflow. Protein expression of P2X receptors (immunoblotting) and co-localization with adrenergic receptors (immunohistochemistry) of the PVN will be also investigated , for a better understanding of the mechanisms involved in NH.
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