The role of the sympathetic nervous system in the pathogenesis of hypertension.

摘要

Recent studies have suggested that hypertensive humans and animal models of hypertension exhibit increased peripheral sympathetic nervous system activity (SNA). Although knowledge of the events that lead to increased SNA and its significance in the genesis and maintenance of elevated blood pressure remains poorly understood, it has been thought that increased SNA may originate primarily from the central nervous system. In contrast, primary abnormalities in the function of the peripheral nervous system (PNS) in hypertension are less well documented. Our general approach to assess the role of the PNS in the maintenance of blood pressure is to monitor the activity-dependent changes in neuroplasticity of the superior cervical ganglia (SCG). This approach has proved fruitful in expanding our knowledge of the sympathetic nervous system and its role in the development of hypertension.;The second component of our research focuses on the interactions between angiotensin II (Ang II) and the phosphoinositide 3 kinase (PI3K) pathway in the nucleus of the solitary (NTS). Previous studies have revealed a PI3K sensitive pathway in the rostral ventral lateral medulla (RVLM) of spontaneously hypertensive rats (SHR). However the role of the PI 3K-dependent Ang II signaling pathway in the NTS has yet to be defined. The NTS is the central site for termination of baroreceptor afferent fibers. This area of the dorsal medulla contains a high density of Ang II type 1 receptors (AT1R); binding of Ang II to the AT1R has been shown to initiate specific Ang II dependent intracellular signaling events in the RVLM via the PI3K pathways. For these reasons, the NTS represents an area of great interest and promise for deciphering the signaling mechanisms responsible for elevated blood pressure and attenuation of the baroreceptor reflex. Thus, our initial goal is to demonstrate whether PI3K signaling pathway in the NTS of hypertensive rats is activated in response to Ang II binding to AT1R. One rationale for the proposed research is to obtain knowledge of the mechanisms that are responsible for the development of hypertension. This type of new information 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.