Central mechanisms involved in the sympathoexcitation in response to hypoxia
Abstract
The neural mechanisms underlying the generation and modulation of the sympathetic outflow and the respiratory motor activities are essential for the physiological regulation of the cardiovascular and respiratory functions and consequently for the maintenance of the life. Changes in any aspect of these complex neural mechanisms may affect the cardiovascular and respiratory functions and generating pathophysiological conditions such as hypertension and obstructive sleep apnea. Taking into account that the groups of neurons underlying both sympathetic and respiratory activities are located in the ventral aspect of the medulla, and also that we have strong experimental evidences of the coupling of these activities, the main purpose of this Program Project Grant (Thematic Project) is to evaluate the neurochemical mechanisms involved in the sympathetic-respiratory coupling, especially under challenges conditions such as the chronic intermittent hypoxia or sustained hypoxia. To reach this goal, we will use several contemporary methods and procedures appropriated to help us to answer the several fundamental questions of this Project. In order to challenge the neural pathways of the peripheral chemo reflex and consequently to induce changes in the sympathetic respiratory coupling, we will use different experimental protocols of hypoxia (intermittent or sustained). To explore the complexity of the neural network involved in the generation of sympathetic and respiratory activities we will use several methods of advanced electrophysiology and cellular biology, which we were able to introduce successfully in our laboratory on the past few years, with the financial support by6FAPESP. On the 11 sub-projects to be developed, we will use from awake freely moving rats to neurons in the slices of the brainstem to evaluated very precise ionic currents that may determine the electrophysiological profile of each group of sympathetic and respiratory neurons in normal and in rats submitted to hypoxia. With this integrated approach from whole animal to isolated neurons, not usual in the large majority of laboratories in the world, we are convinced that the obtained results will contribute very much for a better understanding of the neural mechanisms underlying different pathophysiological conditions such as the neurogenic hypertension. (AU)
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