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Colocalization of the Endothelinergic and Catecholaminergic Systems in Neuronal Activated Groups in the Olfactory Bulbs of Doca-salt Hypertensive Rats

María Julia Guil

Georgia Regents University

Hypertension is a major risk for cardiovascular diseases; it shows high morbidity and mortality rates associated with damage on target organs like the heart, kidney, retina, and the central nervous system (CNS). Hypertension is a complex and multifactorial disease that in most cases has no identifiable underlying cause so it represents a major challenge for scientists.  Most forms of hypertension share a common feature, which is a higher sympathetic outflow, although the reason is presently unknown. In our laboratory, we focus on the study of the relationship between the brain endothelinergic system and noradrenergic transmission and the implication of such interaction in hypertension. In particular, I study the brain interaction between Endothelins and norepinephrine in DOCA-salt hypertension. The contribution of peripheral Endothelins to hypertension has been extensively studies but the role of brain Endothelins remains to be elucidated. The aim of the present research plan is to test the hypothesis that alterations in the interaction between the endothelinergic system and noradrenergic transmission system in different regions and areas of the CNS are partly responsible for DOCA-salt hypertension. The hypothesis is supported by previous studies showing that the central catecholaminergic system is impaired in this model of hypertension and that there is direct evidence that central sympathetic activation plays a crucial role in the development of blood pressure elevation in the DOCA-salt model. In addition, another conclusive finding that endorses the participation of the CNS in DOCA-salt hypertension is that the ablation of different brain regions or areas like the area postrema or the AV3V area prevents its development.  At the lab headed by Dr. Stern I will get trained in various techniques as electrophysiology and confocal real time microscopy in order to evaluate the co-expression and possible interaction between Endothelins and noradrenergic transmission, both in neurons and astrocytes. The obtained results will certainly help to clarify the interaction between endothelinergic and cathecolaminergic systems in experimental hypertension.

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