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Peripheral and Central Regulation of Cardiovascular Functions

Arthur D. Loewy, Ph.D.
Washington University School of Medicine

This lecture will provide an overview of the central autonomic circuits that regulate cardiovascular functions. The discussion will begin with the baroreceptor reflex, which is a negative feedback system that is designed to prevent changes in mean arterial pressure. Its major function is to maintain blood pressure at a particular set-point or average value. However, this simple reflex can be influenced by both circulating plasma levels of arginine vasopressin and angiotensin II, which act directly to influence sympathetic activity as well. In addition, these peptide hormones act at central sites that lack a blood-brain barrier (viz., circumventricular organs, CVOs). The CVOs are localized in the medulla oblongata as well as in selected forebrain sites; they all contain specialized neurons that function as chemosensors and are linked to central circuits that influence both sympathetic and neuroendocrine functions. In the medulla oblongata, the area postrema is the CVO that is sensitive to circulating levels of vasopressin; neurons from this region have been shown to send inhibitory inputs to the nucleus tractus solitarius, the key site in the baroreflex. These data suggest that both neural and humoral signals can act in concert to influence centrally mediated sympathetic activity. The CVOs of the forebrain consist of several regions lying along the anterior limit of the third ventricle, and collectively this general area has been referred to as the "AV3V" region. It is linked to hypothalamic regions that modulate the release of vasopressin and also affect sympathetic activity. Considerable evidence has been collected that has demonstrated its importance in a variety of models of experimental hypertension.

Apart from the central circuits that subserve homeostatic functions, advancements have been made in understanding the neural organization of the emotional-autonomic circuits. These may be particularly relevant in light of clinical evidence that many cardiovascular events occur during the rapid-eye movement stage of sleep and seem to be associated with emotionally provoking dreams. Similarly, there is an increased incidence of life-threatening cardiovascular problems that are associated with the states of anger. Therefore, the central circuits influencing emotional-autonomic responses is a new area of research attracting much interest. Emotions can be produced in laboratory rats that appear to be similar to states of anxiety and fear seen in humans. By stimulating specific regions in the extended amygdaloid complex, researchers have demonstrated particular types of affective responses. These forebrain areas are also connected by multi-synaptic pathways to the cardiac- and adrenal sympathetic outflow systems. The data raise the possibility that common sites in the forebrain may function as a unit in forming integrated emotional-autonomic responses.

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