The long-term objective of the proposed investigation is to understand the mechanisms by which high blood pressure produces profound changes in the physiology of autonomic synaptic transmission. Many studies suggest that hypertensive humans and animal models of hypertension exhibit increased peripheral sympathetic nervous system activity (SNA). Knowledge of the events that lead to elevated SNA and its significance in the genesis and maintenance of elevated blood pressure is rudimentary. It has been thought that increased SNA may originate primarily from the central nervous system. This supported by the efficacy of certain centrally acting drugs, the impact of lesions in regions of the hypothalamus and brainstem involved in cardiovascular and electrolyte homeostasis and the effects of many centrally administered hormones on sympathetic outflow. In contrast, primary abnormalities in the function of the peripheral nervous system in hypertension are less well documented. The general approach is to monitor the activity- dependent changes in neuroplasticity of the superior cervical ganglia (SCG) and stellate ganglia (SG) isolated from hypertensive rat. Our hypotheses are that 1) hypertension induces modulation of synaptic efficacy in sympathetic ganglia, and 2) Angiotensin II (AngII), either by long term actions at the ganglion or by increased activation of sympathetic nervous system (SNS) outflow from the central nervous system (CBS), contributes to the alterations in ganglionic function. In animal models of hypertension, dramatic changes can be observed in the electrophysiological behavior of sympathetic ganglion neurons ranging from alterations in the pattern of action potential activity recorded in postganglionic neurons to an enhanced efficacy of synaptic transmission. Our preliminary data reveal that two forms of synaptic plasticity, namely, post-tetanic (PTP) and long-term potentiation (LTP) in the SCG are profoundly affected during hypertensive states. This proposal uses electrophysiological techniques, receptor autoradiography techniques and neurotransmitter pharmacology in concert with genetic strains of hypertensive animals to learn how genesis and maintenance of high blood pressure alter the function of peripheral neural elements in autonomic ganglia.
| Logan, Exazevia M; Aileru, Azeez A; Shaltout, Hossam A et al. (2011) The functional role of PI3K in maintenance of blood pressure and baroreflex suppression in (mRen2)27 and mRen2.Lewis rat. J Cardiovasc Pharmacol 58:367-73 |
| Aileru, Azeez A; Logan, Exazevia; Callahan, Michael et al. (2004) Alterations in sympathetic ganglionic transmission in response to angiotensin II in (mRen2)27 transgenic rats. Hypertension 43:270-5 |
