Stress, Coping, and Cardiovascular Disease
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Stress, Coping, and Cardiovascular Disease

Philip Mccabe, Neil Schneiderman, Tiffany M. Field, A. Rodney Wellens, Philip Mccabe, Neil Schneiderman, Tiffany M. Field, A. Rodney Wellens

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eBook - ePub

Stress, Coping, and Cardiovascular Disease

Philip Mccabe, Neil Schneiderman, Tiffany M. Field, A. Rodney Wellens, Philip Mccabe, Neil Schneiderman, Tiffany M. Field, A. Rodney Wellens

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About This Book

The latest volume in the series based on the Annual Stress and Coping Symposia held at the University of Miami, Drs. McCabe, Schneiderman, Field, and Wellens bring together an outstanding group of researchers to examine the relationship between bio-behavioral and social factors and heart disease. Highlights of the book include an in-depth look at the latest research on:
* basic physiological processes in cardiovascular reactivity to stress;
* pathophysiological mechanisms in cardiovascular disease;
* ethnic differences in cardiovascular regulation;
* psychosocial influences on cardiovascular function/disease; and
* Behavioral interventions designed to treat cardiovascular disorders. The goal of Stress, Coping, and Cardiovascular Disease is to provide a solid empirical foundation on the relationship between stress and cardiovascular disease so as to stimulate further research into the pathophysiology and treatment of the leading cause of death in industrialized countries.

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Year
2000
ISBN
9781135664039

1
Stress Responses, Coping, and Cardiovascular Neurobiology: Central Nervous System Circuitry Underlying Learned and Unlearned Affective Responses to Stressful Stimuli

Ray W.Winters
Philip M.McCabe
Edward J.Green
Neil Schneiderman
University of Miami

Affective behaviors are evoked when environmental circumstances pose a threat or challenge to an organism. These integrated somatic and visceral response patterns to emotionally significant stimuli allow an organism to adapt to its environment during stressful situations. Our research program has focused on the central nervous system (CNS) mechanisms that underlie the expression of integrated response patterns to environmental stressors and to the sensory mechanisms that mediate learned emotional responses to these environmental challenges. Several working hypothesizes serve as heuristic guides for our studies. One hypothesis is that the autonomic components of learned affective behaviors are mediated by the neuronal circuitry that subserves hard-wired, unlearned responses to emotional stressors, such as the defense reaction. The autonomic components of the defense reaction serve to prepare the organism for “fight or flight.” Fight or flight behaviors are not appropriate for the psychosocial stressors that humans face, and although humans do not typically engage in these behaviors, the response patterns of the autonomic nervous system associated with them are still evoked by psychosocial stressors. As a case in point, the cardiovascular responses elicited during the preparation for a stressful speech task are the same ones evoked during the defense reaction, although they clearly exceed the metabolic demands of the task. In general, the autonomic responses elicited to psychosocial stressors are the same ones evoked during unlearned responses to emotional stressors, although they are not always the ones associated with the defense reaction. The observation that these responses exceed the metabolic demands of the task has led a number of investigators to suggest that this is a factor in the etiology of stress-related diseases.
What types of studies must the behavioral neuroscientist conduct to advance the understanding of the CNS mechanisms that underlie emotional responses to psychosocial stimuli? We believe that four types of studies must be conducted. First, it is necessary to delineate the functional pathways in the brain that subserve hard-wired affective behaviors, such as the defense reaction. One of our goals since the late 1970s has been to chart the CNS pathway of the defense reaction, using the rabbit as an animal model. We have also mapped many of the elements of a pathway associated with a second type of autonomic- behavioral response pattern to emotional stressors, referred to as the vigilance reaction.
A second type of question that emerges concerns how an event or a set of circumstances (e.g., the preparation for a speech, a job interview) that initially is emotionally neutral becomes affectively significant to the individual so that it evokes an emotional reaction. This, of course, concerns mechanisms of appraisal, learning, and memory. A second goal of our research program has been to delineate the sensory pathways that allow a neutral stimulus to evoke an affective response.
Two other questions are important to the understanding of the brain mechanisms that mediate affective behaviors. As suggested by numerous students of emotions, there must be mechanisms in the brain that allow the organism to appraise the emotional significance of stimuli, whether they are unconditioned or conditioned stimuli. That is, the relevance of an event to one’s well-being must be determined before an emotional reaction can occur. In this chapter, we present evidence that the amygdala is a part of the neuronal circuitry necessary for the assignment of emotional significance to sensory events and linking these stimuli to appropriate behaviors. Also presented is evidence that the amygdala is a nodal structure for feedback signals evoked by emotional responses, particularly those sent by baroreceptors and chemoreceptors. Feedback signals from baroreceptors and chemoreceptors are thought to modulate the intensity and duration of an affective behavior and may do so, at least in part, by their effects upon the neuronal circuitry involved in appraisal. Because the feedback signals from baroreceptors attenuate affective responses, the increases in blood pressure that generate these signals may become a conditioned response in stressful situations in which coping responses are not available, thereby attenuating the emotional reaction by their effects on the appraisal mechanism. Also presented is evidence that the effects of peripheral feedback on the strength of the memory trace, developed during experiences that have emotional significance, are mediated by the amygdala. In this way, the intensity of an emotional reaction to various events becomes a factor in determining the strength of memory traces that might be stored. Once again, these effects are thought to be mediated by a nodal structure involved in appraisal, the amygdala.
Finally, in order to understand the brain mechanisms involved in learned affective behaviors, the investigator must determine the CNS structures that form the bridge between the circuitry underlying conditioning and learning, as well as the circuitry that mediates the autonomic components of preprogrammed responses, such as the defense reaction. In this chapter, we present evidence that the hypothalamus is essential to the circuitry that mediates the expression of the autonomic components of affective behaviors in response to conditioned stimuli.

Clinical Significance

Pharmacological treatments and clinical interventions such as neuromuscular relaxation techniques, paced respiration, and exercise are believed to attenuate general arousal (Taylor, 1978), or sensitivity at specific CNS sites, such as the hypothalamus or amygdala, which are nodal structures in the integration and regulation of responses to emotional stressors (Benson, 1983; Gellhorn & Kiely, 1972). These interventions have been found to lead to changes in sympathetic tone (Benson, 1983), cardiovascular reactivity (Allen, 1981), or the recovery rate of cardiovascular responses to a stressor (English & Baker, 1983; Goleman & Schwartz, 1975). Accordingly, one objective of our research program is to provide a neurobiological framework to study human cardiovascular reactivity and to provide an empirical foundation for the development of pharmacological and behavioral interventions that may be employed in the prevention and treatment of cardiovascular disease.

Integrated Coping Responses to Emotional Stressors

Human psychophysiology studies reveal at least two distinct cardiovascular response patterns to laboratory stressors. The first response pattern, that is seen during stressful speech preparation, for example, is characterized by increased cardiac output and a small decrement, or no change, in total peripheral resistance (Hurwitz, Nelesen, Saab, Nagel, Spitzer, Gellman, McCabe, Phillips, & Schneiderman, 1993; Saab, Llabre, Hurwitz, Frame, Fins, McCalla, Cieply, & Schneiderman, 1992). The second pattern of response, seen during the mirror star-tracing task or during the cold pressor task, is characterized by increases in total peripheral resistance with a decrease in cardiac output (Hurwitz et al., 1993; Saab et al., 1992). Interestingly, the same two response patterns have been observed by investigators who use animal models to assess cardiovascular responses to stress (Schneiderman & McCabe, 1985) and are referred to as the defense reaction and vigilance reaction, respectively. Moreover, there is convincing evidence that the pattern of cardiorespiratory activity elicited by stressful or threatening situations in animals is dependent on the availability of a coping response. The behavioral-cardiorespiratory pattern of activity shown when a coping response is available to the animal, the defense reaction, is characterized by cardiovascular and respiratory changes that serve to prepare the animal for fight or flight, that is, increases in cardiac output, heart rate, blood pressure, and hindlimb blood flow, coupled with hyperventilation (Abrahams, Hilton, & Zbrozyna, 1960, 1964; Bolme, Ngai, Uvnas, & Wallenberg, 1967; Smith, Astley, DeVita, Stein, & Walsh, 1980) and inhibition of the cardiomotor component of the baroreceptor reflex. If a coping response is unavailable, the animal shows a behavioral-cardiorespiratory response pattern associated with the inhibition of movement and hypervigilance. This pattern, referred to as the vigilance reaction, is characterized by a pressor response that results from an increase in the total peripheral resistance, but not an increase in cardiac output, bradycardia, the facilitation of the baroreceptor reflex, and inspiratory apnea (Duan et al., 1996b; McCabe et al., 1994). A major objective of our research program is to chart the functional neuroanatomical pathways that mediate the cardiovascular components of these two responses to emotional stressors, using the rabbit as an animal model.
Because the stimuli that elicit emotional behaviors in humans are usually the result of learning experiences, it is also important to understand how coping responses are elicited by conditioned stimuli. A second objective of research from our laboratory, therefore, is to further the understanding of the CNS mechanisms that mediate learned emotional responses. We also use the rabbit as an animal model for these experiments. This chapter provides a summary of what we have learned from our efforts since the 1970s and the relation that our findings bear to research from other laboratories that seek to advance our understanding of the CNS substrates of emotional behavior. The conceptual framework used is primarily based on feedback control theory (Powers, Clark, & McFarland, 1960). CNS structures are examined in terms of their roles in the mediation and modulation of affective behavior and how their activity is modified by sensory feedback from visceral afferents. Similarly, learned emotional responses are assessed in terms of their regulatory functions.

Overview of the Nervous System

The nervous system can be defined as a complex network of billions of neurons that regulate internal bodily functions and provides a means for an organism to adapt to the external environment. In order for an organism to regulate interactions with the external environment and maintain a stable internal milieu, information must flow to and from the brain and spinal cord. The brain and spinal cord communicate with the body’s muscles and glands via the cranial and spinal nerves. These nerves, are part of the peripheral nervous system, convey sensory information to the CNS and send messages from the CNS to the muscle tissue and glands. Neurons within the cranial and spinal nerves that transmit information to the CNS are referred to as afferent neurons; they are activated by receptors located in sense organs, such as the eye, or within the body itself, such as the baroreceptors and chemoreceptors located in the blood vessels. These neurons provide the CNS with information regarding changes in the internal and external environment and with feedback signals to apprise the CNS of the consequences of its command to change the organism’s behavior or activity in an internal organ. Efferent neurons in the cranial and spinal nerves transmit information from the CNS to striated (skeletal) muscles in order to move the limbs, to the smooth muscle of internal organs, to glandular tissue, and to cardiac muscle. The target organ of efferent neurons of the somatic motor system is striated muscle. The target organs of the efferent neurons of the autonomic nervous system are the smooth muscle of internal organs, the glands, and the heart. The primary function of the autonomic nervous system is the regulation of internal body functions; it is particularly important to behavioral scientists because of its involvement in the expression of emotions.
The nervous system is composed of numerous interconnected subsystems of neurons involved in the regulation of various behaviors and physiological functions. In this context, a neuronal subsystem is defined as a network of nuclei and axonal pathways serving a common function. For example, there are separate networks of neurons concerned with movement, emotions, motivation, attention, arousal, cognition, and various sensory functions, such as vision, hearing, taste, and smell. The characterization of the CNS neuronal subsystems involved in the regulation of learned and unlearned emotional behaviors is the focus of our research program.

Organization of the CNS

Superficially, the brain looks like a mushroom. It has a stem, referred to as the brainstem, and an overlying cap, the cerebral hemispheres; the cerebellum lies between the brainstem and the posterior portion of the cerebral hemispheres. The spinal cord is a caudal extension of the brainstem. Information about the external environment and feedback about a person’s behavioral and internal bodily responses are sent to the spinal cord, brainstem, cerebellum, and cerebral hemispheres to activate various subsystems of neurons, such as those concerned with memory, attention, control of movement, and emotion.
The brain is usually discussed in terms of three neuroanatomical subdivisions: the forebrain, midbrain, and hindbrain. The hindbrain consists of two major divisions, the medulla (myelencephalon) and the pons and cerebellum (metencephalon). The medulla, which is the most caudal portion of the brainstem, contains nuclei that are involved in the control of vital functions such as regulation of the cardiovascular and respiratory systems, the maintenance of skeletal muscle tone, and arousal. The cerebellum receives information from several sensory modalities and integrates this information to allow for smooth, coordinated movements. Damage to this area leads to jerky movements and can impair the ability to walk or even stand. The pons is considered to be the bridge between the cerebellum and the structures in the midbrain, forebrain, and medulla. It also contains nuclei that are part of neural subsystems involved in the regulation of arousal and sleep.
Some of the most complex functions of the brainstem are mediated by neurons in the midbrain. The midbrain contains nuclei that are part of neural subsystems that mediate fixed, stereotyped, ritualistic behaviors that are essential for survival and reproduction. As a case in point, both the defense and vigilance reactions can be elicited by electrical or chemical stimulation of the periaqueductal gray (PAG), a central structure in the midbrain.
The forebrain plays a major role in behaviors that require complex processing (e.g., the storage and retrieval of memories, the integration of emotional experiences and coping behaviors, the coordination of complex movements, and the cognitive processing of information). Affective behaviors, such as the defense and vigilance reactions, are modulated by forebrain structures, and the acquisition of learned affective behaviors require the activation of neuronal subsystems in the forebrain.

CNS Structures Involved in Affective Behaviors

The basic organizational plan of the brain and spinal cord is a network of neuronal cell body clusters (nuclei or gray matter) interconnected by bundles of neuronal axons (tracts or white matter) and organized into neuronal subsystems that have separate functions. Our research program seeks to map the neuronal subsystems that mediate the cardiovascular components of the defense and vigilance reactions and those that underlie learned emotional responses. This section of the chapter provides a brief review of what is known about the CNS regions we have encountered in our studies of affective behavior.

Spinal Cord Structures

Intermediolateral Cell Column (IML). The cell bodies of the preganglionic neurons of the sympathetic division of the autonomic nervous system are located in the intermediolateral cell column of the thoracic and lumbar portions of the spinal cord. The axons of these efferent neurons connect to postganglionic neurons of the sympathetic nervous system located in either the sympathetic trunks, adjacent to the spinal cord, or to ganglia located near internal organs. These neurons are particularly important to cardiovascular regulation because they connect to the heart and the smooth muscle of blood vessels.

Hindbrain Structures

The Rostral Ventrolateral Medulla (RVLM). The RVLM is a cluster of cell bodies in the medulla that plays a central role in setting the resting level of blood pressure by influencing the tonic contractile state of blood vessels (vasomotor tone). This structure is also involved in the mediation of phasic changes in blood pressure and heart rate. The RVLM is also a part of the neuronal subsystem that regulates blood pressure, known as the baroreceptor reflex.
Dorsal Motor Nucleus of X (Dun) and Nucleus Ambiguus. The cell bodies of the preganglionic neurons of the parasympathetic division of the autonomic nervous system are located in the brainstem and the sacral portion of the spinal cord. The axons of these efferent neurons, therefore, are found in cranial nerves and spinal nerves. The tenth cranial nerve, the vagus nerve, is particularly important to cardiovascular regulation because many of its axons connect to the heart. The cell bodies of these efferent neurons are found in nucleus ambiguus and the dorsal motor nucleus of the vagus nerve (DVN). They are a component of the reflex arc that mediates the cardiomotor component of the baroreceptor reflex. The vagus nerve also contains afferents that provide visceral sensory information to the CNS, thereby providing feedback about visceral responses that occur during affective behavior.
Nucleus of the Solitary Tract (NTS). This cluster of cell bodies receives sensory information from visceral organs. As discussed later in this chapter, there is evidence that visceral sensory information conveyed to the NTS modulates the storage of memories that have emotional significance to the organism. The NTS is also a part of the baroreceptor reflex arc, receiving information from baroreceptors located in blood vessels and sending information to CNS structures that lead to changes in vasomotor tone and cardiac output, to regulate blood pressure.
Medullary Raphe. The neurons situated along the midline of the medulla, pons, and midbrain are collectively referred to as the raphe nuclei. A substantial number of the raphe neurons secrete the synaptic transmitter serotonin. The raphe neurons in the medulla project to the spinal cord and are best known for their role in the modulation of neurons that transmit pain information. Electrical stimulation of medullary raphe also inhibits the activity of sympathetic preganglionic neurons located in the IML of the spinal cord.
Lateral Tegmental Field of the Medulla (LTFM). Although the LTFM is believed to be involved in cardiovascular regulation, its exact role is unknown. One view is that these neurons are a source of excitatory input to RV...

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