Stress and Hypertension

YALE UNIVERSITY PRESS

Contents

Chapter One

Blood has long been recognized as a vital body fluid. Prehistoric humans must have observed the spillage of blood that followed aggressive exchanges or accidents and quickly learned that loss of blood resulted in death. It is not surprising, then, that early physicians, including Hippocrates and Galen, placed a great deal of importance on defining blood as an essential bodily humor and that the examination of the pulse was described as the most important component of a correct medical diagnosis in The Yellow Emperor's Classic of Internal Medicine, which dates back to medical traditions in China around 2700 B.C. (for a recent translation, see Ni, 1995). Although modern medicine recognizes these early belief systems as being overly simplistic and often mystical in nature, the importance of the circulation of blood in sustaining life among virtually all vertebrate and invertebrate animals is a known scientific fact.

Our modern understanding of the human circulatory system is generally credited to William Harvey (1628/1941). Influenced by empirical study of the dissection of animals, he demonstrated that the circulation of blood worked like a hydraulic water-pumping system. In this regard, circulation of blood was conceptualized as a closed system containing blood that traverses a complex set of blood vessels to transport oxygen and nourishment to every type of cell in the body as well as to remove cellular waste products. The heart worked like the pump in the hydraulic water-pumping system, orchestrating the rate of blood flow throughout the entire circulatory system. As in the hydraulic pumping system, pressure could be increased within the system to force the fluid (blood in this case) to flow in any direction, even against the force of gravity. What is called water pressure in a hydraulic water-pumping system is referred to as blood pressure in the circulatory system. Blood pressure clearly differs at various locations in that system. For example, blood pressure is much higher in the vessels through which it flows immediately after leaving the heart (arterial pressure) than in the vessels through which it flows as it reenters the heart (venous pressure). This difference in blood pressure is clearly evident when injuries result from severed arteries or veins. Most of the minor injuries individuals sustain throughout life involve severed veins close to the surface of the skin. In these types of injuries, blood oozes out, and blood flow can generally be stopped with gentle external pressure at the site of the wound, although it may take a few minutes. Arterial damage, in contrast, is a more dangerous situation; in this type of injury, blood ejects from the wound, pulsing with the beating of the heart. Failure to respond adequately to arterial injuries will quickly result in bleeding to death. The greater blood pressure within arteries versus veins is responsible for the rapid loss of huge amounts of blood with arterial injuries.

An organism can generate additional blood cells to release into circulation (increasing the density of circulating blood cells) or alter the resistance to the flow of blood by constricting or dilating blood vessels. Therefore, in contrast to the relatively stable water pressure that can be maintained in a hydraulic water-pumping system, blood pressure is constantly changing as the body creates and releases new blood cells and alters blood flow resistance. Additionally, because the heart does not pump blood continuously as a water pump does, blood pressure differs while the heart is pumping and while the heart is at rest. The higher arterial pressure observed during heart action (ejection of blood from the heart) is referred to as systolic blood pressure (SBP), and the lower arterial pressures that occur during rest just prior to the next heart beat (while blood refills the heart) is referred to as diastolic blood pressure (DBP). Obviously, the circulation of blood is much more complicated than early physicians thought! Before addressing the relation between stress and hypertension, let's take a look at what we know about the structure and function of the various components of the circulatory system that affect blood pressure.

Physiology of the Circulatory System

It is likely that your blood pressure is different right now from what it was when you started reading this chapter. The difference may not be substantial, but due to the complexity of factors that affect blood pressure, it constantly changes in response to a number of physiological and environmental stimuli. For example, drinking a caffeinated or alcoholic beverage could influence your blood pressure while you read this page. Smoking a cigarette would have the same result. Your blood pressure will also differ if you are watching television while reading this page or if you are interacting with another person. Even the simple act of reading affects your blood pressure. In fact, given the constant adjustments in blood pressure that occur, we really should not refer to an individual's blood pressure as a stable medical parameter.

As depicted in Figure 1.1, blood pressure is jointly determined by the amount of blood ejected into circulation (cardiac output) and the forces of the circulatory system that impede blood flow (total peripheral resistance). Increases in either cardiac output or total peripheral resistance will result in increased blood pressure. Cardiac output, in turn, is determined by heart rate and stroke volume (amount of blood ejected from the heart with each stroke). Again, increases in either heart rate or stroke volume will increase cardiac output, and thus blood pressure. Total peripheral resistance is comprised of the degree of vasodilation and vasoconstriction that occurs in the various blood vessels that compose the entire peripheral circulation. All of these hemodynamic parameters (heart rate, stroke volume, cardiac output, total peripheral resistance) rarely operate in the same direction. Increased heart rate, for example, is often accompanied by a reduction in stroke volume, potentially resulting in no change in cardiac output or blood pressure at all. However, all physiologic or psychological states that affect blood pressure will do so by altering cardiac output, total peripheral resistance, or some combination of the two.

Several systems of the body directly influence blood flow through the body and the magnitude of blood pressure, including: (a) the metabolic demands of the local tissue and associated blood vessels, (b) the autonomic nervous system, (c) the neuroendocrine system, (d) the excretion of fluid by the kidney, and (e) an extensive feedback system that involves central nervous system activity. To illustrate these various interrelated systems, let's consider what happens to blood flow when a person engages in a bout of moderate exercise, like jogging on a treadmill, riding a bicycle, or taking a vigorous walk. Obviously, blood flow will need to increase to support the metabolic demands of the leg muscles, delivering more oxygen and nutrients while removing the waste by-products from the muscle cells of the legs. Unusually, although heart rate increases significantly during moderate exercise, very little change in diastolic blood pressure is typically observed (Kasprowicz et al., 1990). Therefore, during exercise, the body must engage in a variety of regulatory processes to maintain blood pressure in light of the increased cardiac activity. To provide an exhaustive overview of the physical, chemical, and neural elements involved in the regulation of blood pressure is clearly beyond the scope of this chapter and book. The following sections are meant to represent only an overview of the major systems involved in the regulation of blood pressure illustrated in Figure 1.2. The interested reader is referred to Kaplan (2002) for a more complete description of the physiological mechanisms that affect blood pressure regulation.

Effects of Local Body Tissue on Blood Pressure

Because the oxygen and waste removal requirements of the muscle cells change in response to exercise, local body tissues (blood vessels that serve muscle cells) possess an intrinsic capability to regulate local blood flow. Through a process known as autoregulation, local blood vessels dilate or constrict in response to the prevailing blood pressure at that site in the vascular bed and the metabolic needs of the local cells to assure that appropriate blood flow is maintained. In this regard local factors in one part of the circulatory system can maintain blood flow under conditions of heightened blood pressure, while appropriate blood flow can be maintained in other parts of the circulatory system under conditions of reduced blood pressure. What this suggests is that although blood flow is affected by signals from the nervous and neuroendocrine systems (described below), blood flow also can be regulated locally in the absence of these influences (see dotted arrow in Figure 1.2). Under conditions of exercise or physical exertion, blood flow increases to the striate muscles due to the increased metabolic demand of those tissues.

In recent years, increased attention has been paid to the identification of the mechanisms involved in the local regulation of blood flow. Nitric oxide, for example, has been isolated as a 'relaxing' factor that operates as a vasodilator released by local blood vessels in the circulatory system based upon the prevailing blood pressure at those sites (Palmer, Ferrige, and Moncada, 1987). As pressure increases are detected in local blood vessels, nitric oxide is released, causing the vessel to dilate and lower blood pressure. This action presumably explains how diastolic blood pressure remains relatively unaffected during cardiovascular activation that accompanies bouts of exercise. Unfortunately, circulating proteins, like C-reactive protein, that increase one's risk for atherosclerosis, appear to reduce quantities of nitric oxide, preventing adaptive blood pressure regulation at the local level (Ridker, 1998).

The Role of the Nervous System in Blood Pressure

Many fluctuations in blood flow occur as a result of alterations in signals the circulatory system receives from the nervous system. As depicted by the solid arrows in Figure 1.2, the brain communicates with various organs in the circulatory system through the autonomic nervous system. This system is comprised of two separate systems called the sympathetic nervous system and the parasympathetic nervous system. The former directs what is frequently called the 'fight-flight' response, and the latter directs what has been called the 'relaxation response.' Although initially it was thought that these two systems were interconnected (as sympathetic nervous system activity increases, parasympathetic activity decreases), it is now known that they can operate independently. In this regard, sympathetic and parasympathetic influences can work simultaneously to affect the target organs in the body. The sympathetic nervous system employs two distinct neural systems that affect blood pressure, known as the alpha-adrenergic and beta-adrenergic systems. The alpha-adrenergic neurotransmitters and receptor systems affect blood vessels by causing them to constrict, whereas the beta-adrenergic system affects both the heart and the blood vessels. Beta-adrenergic activity leads to increased heart pumping action (increased heart rate) as well as vasodilation of blood vessels. This combination of neural influences represents an adaptive response, as the increased blood flow caused by the increase in heart rate needs more space in the vasculature in order for blood pressure to be properly regulated. The parasympathetic nervous system influences only the heart via the vagal nerve, which results in slowed heart rate. In sum, these components of the autonomic nervous system interact to regulate blood pressure with the aim of keeping it within adaptive limits. During the type of exercise described above, heart rate will increase accompanied by vasodilation of the blood vessels in the leg muscles mediated by the beta-adrenergic system. This response pattern permits increased delivery of oxygen to the leg muscles without a concomitant alteration in local diastolic blood pressure. At the same time, blood flow to the gastrointestinal system is likely reduced via vasoconstriction, as digestion is not an important use of the body's resources during a bout of exercise.

The Role of the Endocrine System in Blood Pressure

Blood pressure is also affected by various hormones of the neuroendocrine system, particularly norepinephrine (noradrenalin), epinephrine (adrenalin), and cortisol (see dashed lines in Figure 1.2). Stimulation of the sympathetic nervous system leads to the release of the catecholamines, epinephrine and norepinephrine, from the adrenal medulla and of the corticosteroid, cortisol, from the adrenal cortex. Unlike the immediate action of the autonomic nervous system described above, the neuroendocrine response is a little slower. In contrast to the direct neural pathways of the autonomic nervous system to the various elements of the circulatory system, the neuroendocrine response relies on the circulatory system itself to transport hormonal secretions to various target organs and receptors. Norepinephrine generally results in increased vasoconstriction while epinephrine results in the dilation of vessels adjacent to muscle cells. Both epinephrine and norepinephrine increase heart rate. During a bout of exercise, epinephrine exerts a significant vasodilatory effect on the blood vessels associated with the skeletal muscles. Corticosteroids, including cortisol, also have an effect on blood pressure. Without the presence of cortisol, the influence of epinephrine and norepinephrine upon vascular responses is minimized (Drew and Leach, 1971). Therefore, cortisol facilitates the action of the catecholamines.

Renin, a humoral substance produced in the kidneys, also influences blood flow by converting angiotensin to angiotensin II, another vasoconstrictive hormone. Angiotensin II then signals the adrenal cortex to secrete aldosterone, which causes the body to retain sodium. Sodium retention causes the body to retain fluid, resulting in an increase in blood volume and thus increased blood pressure. There are numerous other hormones that affect blood pressure, operating as either vasoconstrictive or vasodilatory agents. The reader is referred to a full description of them in Kaplan (2002).

The Effect of the Kidney on Blood Pressure

The kidneys are organs that are ultimately responsible for the amount of fluid the body retains, and thus exert a significant effect on regulating blood volume and blood pressure. Increased blood pressure detected by the kidneys results in increased urinary excretion, and reductions in blood pressure result in lowered excretion rates, both regulating blood pressure by altering blood volume. During the bout of exercise, however, a portion of the blood volume is absorbed into muscle and skin cells and fluid excreted via sweat glands, rather than the kidneys alone regulating body fluid.

As stated above, the kidneys also affect blood pressure through release of renin. Essentially, when the kidneys detect a drop in blood pressure, renin is released, leading to increased vasoconstriction and sodium retention that elevate blood pressure to its previous level. This renin-angiotensin-aldosterone system, then, represents an important feedback system involved in blood pressure regulation.

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Excerpted from Stress and Hypertensionby Kevin T. Larkin Copyright © 2005 by Yale University. Excerpted by permission.
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