Evaluation of PI3K expression and its interaction with angiotensin on central autonomic nuclei of hipertensive animals

Abstract

The central nervous system (CNS) plays an essential role on the pathogenesis of the hypertension. It is possible to assume that the causes of this pathology are closely associated to changes in the expression of genes network as well as in the molecular and biochemical signalling of specific autonomic nuclei of the hypothalamic-brainstem circuitry that control the cardiovascular reflexes and sympathetic activity (SNA). Among these nuclei are the hypothalamic paraventricular nucleus (PVN), the nucleus of the solitary tract (NST) and the rostroventrolateral medulla (RVLM). Recent studies performed with gene microarray technique have identified that the phosphoinositide 3-kinase (PI3K) gene is up-regulated within the three brain autonomic nuclei of spontaneous hypertensive rats (SHR) when compared with its normotensive controls (WKY). Such gene is responsible for expressing the PI3K protein that is directly linked to the intracellular signalling of the angiotensin II (ANG II) pathways, acting via AT1 receptors, which is considered one of the most important endogenous neuromodulator involved in the neural control of the blood pressure. Based on these results, the aim of the present project is to evaluate the differences on the PI3K expression as well as its interaction with angiotensin in the PVN, NTS and RVLM on the pathogenesis of hypertension in SHR and upon an experimental animal model of hypertension with overactivity of the renin-angiotensin system, induced by the aortic coarctation.