Central And Peripheral Mechanisms Of Cardiovascular Regulation

There is increasing awareness that the autonomic nervous system, through its central and peripheral pathways, plays a critical role in the regulation of the circulation. Peripherally, the autonomic representation, largely that of sympathetic nerves, innervate virtually all segments of the vascular tree as well as the adrenal medulla. Through the interaction of nerve terminals, their transmitters, receptors and intracellular mediators in smooth muscle, sympathetic neurons control vascular tone as well as the basal performance of the heart. In turn, the performance of the autonomic nervous system is highly controlled by the brain. Once viewed as a black box with only a vague influence on cardiovascular performance, the introduction of concepts and techniques of neuroscience into the field of cardiovascular medicine has led to the realization of the critical role of this organ in cardiovascular control. It is now well recognized that within the brain, the represenation of cardiovascular function is highly restricted anatomically, engages a number of specific transmitters for its actions, and has highly selective and topographically restricted functions to influence circulatory performance.

Neural Mechanisms of Cardiovascular Regulation responds to current questions about how neurons in the central and peripheral nervous systems regulate the cardiovascular system. It includes a series of thoughtful reviews that are intended to provoke and illuminate the reader, with the intention of revealing some of the ideas that current practitioners in the field of cardiovascular research are using to generate their current studies.

This presentation describes various aspects of the regulation of tissue oxygenation, including the roles of the circulatory system, respiratory system, and blood, the carrier of oxygen within these components of the cardiorespiratory system. The respiratory system takes oxygen from the atmosphere and transports it by diffusion from the air in the alveoli to the blood flowing through the pulmonary capillaries. The cardiovascular system then moves the oxygenated blood from the heart to the microcirculation of the various organs by convection, where oxygen is released from hemoglobin in the red blood cells and moves to the parenchymal cells of each tissue by diffusion. Oxygen that has diffused into cells is then utilized in the mitochondria to produce adenosine triphosphate (ATP), the energy currency of all cells. The mitochondria are able to produce ATP until the oxygen tension or PO2 on the cell surface falls to a critical level of about 4–5 mm Hg. Thus, in order to meet the energetic needs of cells, it is important to maintain a continuous supply of oxygen to the mitochondria at or above the critical PO2 . In order to accomplish this desired outcome, the cardiorespiratory system, including the blood, must be capable of regulation to ensure survival of all tissues under a wide range of circumstances. The purpose of this presentation is to provide basic information about the operation and regulation of the cardiovascular and respiratory systems, as well as the properties of the blood and parenchymal cells, so that a fundamental understanding of the regulation of tissue oxygenation is achieved.

High blood pressure disease is one of the most prevalent pathological conditions in modem society with potentially serious consequences. During the last two decades major progress has been made in the development of rational approaches to the treatment of high blood pressure. A key factor in this progress has been an increase in our understanding of how the brain controls blood pressure. The chapters in the present book, together with those in a previous volume, provide a broad overview of recent progress in our knowledge of the central neural mechanisms involved in the regulation of the cardiovascular system. It is our hope that these essays by leading experts in the field will not only provide a useful source of information, but will also stimulate inquiry leading to new discoveries in this critically important field of research. George Kunos John Ciriello vii List of Contributors Jeffrey J. Anderson, Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46208, USA Katsuyuki Ando, Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo 112, Japan Jaideep S. Bains, Department of Physiology, Queen's University, Kingston, Ontario, Canada K7L 3N6 Kathleen H. Berecek, Department of Physiology and Biophysics and the Vascular Biology and Hypertension Program, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA Vernon S. Bishop, Department of Physiology, The University of Texas Health Science Center, San Antonio, Texas 78284-7756, USA P. A.

The most prominent function of the central nervous system is the control of motor functions by rapidly transmitted impulses through efferent cranial and spinal peripheral nerves. Besides electrically transmitted neural impulses, humoral mechanisms with more sustained actions are exercised by the brain and spinal cord to regulate body homeostasis. Thus, the brain may be regarded as an "endocrine gland" discharging neurohormones (peptides) either into the general circulation (neurohypophyseal hormones) or into the hypothalamo-adenohypophyseal portal circulation (releasing and inhibiting hormones). The brain, therefore, which is protected by the blood-brain barrier from disturbing and potentially noxious exogenous and endogenous agents circulating in the blood, has to have certain neurohemal regions beyond this barrier, such as the neural lobe and the median eminence (infundibulum), where neurohor mones have free access to the blood stream. To regulate somatic and autonomic functions in the best possible way, the central nervous system is highly dependent on feedback signals conveyed through somatic and visceral afferent nerves as well as on peripheral humoral signals such as peripheral hormones and other circulating substances that are under homeostatic regulation, e. g. , peptides, arnines, electrolytes, and other biologically active agents. In this chapter, the role of the blood-brain barrier in the regulation of these sub stances will be discussed with special emphasis on the access through the blood-brain barrier to cardiovascular centers. 2 The Blood-Brain Barrier 2.

With the help of recent technological advances in the study of cen­ tral nervous system function, important strides have been made in our knowledge regarding the pathophysiology of high blood pres­ sure. The understanding of neural mechanisms involved in the reg­ ulation of the cardiovascular system is of critical importance to the development of rational approaches to both the treatment and pre­ vention of this disease. It was in this spirit that a satellite symposium of the 13th Scientific Meeting of the International Society of Hyper­ tension was held in June 1990, in Bethesda, Maryland. The chapters, in this first of two volumes on the same general theme, are based on lectures presented at the symposium and it is hoped that these sum­ maries of recent research findings from prominent laboratories around the world will provide a stimulus for future research. The symposium would not have been possible without generous support from the National Institute on Alcohol Abuse and Alcoholism, Merck Frosst Canada, G. D. Searle Co. , Squibb Institute of Medical Research, Smith, Kline & Beecham Co. , Pfizer Co. , E. I. Dupont de Nemours Co. , Merck, Sharp & Dohme Co. , The UpJohn Co. , and Wyeth-Ayerst Co. While this volume was being prepared for publication, one of its contributors, Dr. Michael J. Brody, died suddenly. It is with deep sorrow and sympathy that we mourn the loss of our colleague. Dr.