The Role of Signal Transduction Pathways in Hypertension

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DESCRIPTION (provided by applicant): The goal of the planned research is to either confirm or refute the presence of separate phosphatidylinositol 3 (PI3) and mitogen-activated protein (MAP) kinase pathways in the nucleus tract solitarius (NTS) in various models of hypertension. The overall objective is to investigate the signaling mechanisms at this brain site potentially contributing to development and maintenance of sustained hypertension. Our ongoing studies are designed to provide initial information about the relationship between the apparent enhancement of the sympathetic nervous system in various forms of hypertension and the role of PI3 and MAP kinase signaling pathways in the maintenance of hypertension. Our initial goal is to demonstrate that PI3 and MAP kinase signaling pathways in the NTS of (mRen-2)27 transgenic rats are activated in response to Ang II binding to AT1 receptors. The rationale for the proposed research is that, once knowledge of the mechanisms that are responsible for the development of hypertension has been obtained, it may lead to new strategies that can be used to prevent and/or treat hypertension, thereby reducing the morbidity and mortality associated with high blood pressure.