Cardiovascular Regulation

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.

The Studies in Physiology series provides a concise introduction to developments in complex areas of physiology for a wide audience. Published on behalf of the Physiology Society, Cardiovascular Regulation provides an up-to-date account of our current understanding of the control of the cardiovascular system that is not covered by existing textbooks. Both students and lecturers of cardiovascular and exercise physiology, medicine, dentistry and biomedical sciences will find this book informative and easy to read. Each chapter has numerous summary boxes. 'Essential reading' suggestions provide additional reading for undergraduates and the suggestions for 'Further reading' cover the subject to postgraduate level.

Contractility describes the relative ability of the heart to eject a stroke volume (SV) at a given prevailing afterload (arterial pressure) and preload (end-diastolic volume; EDV). Various measures of contractility are related to the fraction as the SV/EDV or the ejection fraction, and the dynamics of ejection as determined from maximum pressure rise in the ventricles or arteries or from aortic flow velocities determined by echocardiography. At the cellular level, the ultimate determinant of contractility is the relative tension generation and shortening capability of the molecular motors (myosin cross-bridges) of the sarcomeres as determined by the rates and extent of Ca activation, the turnover kinetics of the cross-bridges, and the relative Ca responsiveness of the sarcomeres. Engagement of the regulatory signaling cascades controlling contractility occurs with occupancy and signal transduction by receptors for neurohumors of the autonomic nervous system as well as growth and stress signaling pathways. Contractility is also determined by the prevailing conditions of pH, temperature, and redox state. Short-term control of contractility is fully expressed during exercise. In long-term responses to stresses on the heart, contractility is modified by cellular remodeling and altered signaling that may compensate for a time but which ultimately may fail, leading to disorders.

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.

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.

Research centering on blood flow in the heart continues to hold an important position, especially since a better understanding of the subject may help reduce the incidence of coronary arterial disease and heart attacks. This book summarizes recent advances in the field; it is the product of fruitful cooperation among international scientists who met in Japan in May, 1990 to discuss the regulation of coronary blood flow.

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.

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.