9.1. Heart Rate
The rate at which a normal adult heart completes one cardiac cycle, during rest, is approx 70 beats per minute (6). This heart rate is maintained at this relatively constant value via a continuous firing of the vagus nerve, called basal (or vagal) tone. The heart rate will increase when vagal tone is overcome by increased activity of sympathetic nerves to the heart, which release norepinephrine and cause a rise in the sinoatrial nodal depolarization rate (Fig. 5). An increase of this nature is referred to as a positive chronotropic effect.
As stated above, the fundamental cause of this increase in heart rate is an increase in activated calcium channels in myo-cardial cell membranes, increasing the speed at which depolarization occurs. This increased sympathetic outflow can be initiated by a large array of internal and external stimuli, including but not limited to exercise, an increase in body temperature, trauma, or stress. In addition, a concurrent release of epineph-rine from the adrenal medulla can further amplify the same effects on myocardial ion channels, although to elicit a significant rise in heart rate the amount of the hormone liberated must be fairly substantial (6).
Parasympathetic discharge increases potassium ion permeability in cardiac myocytes, thus increasing the threshold for depolarization to occur spontaneously in the sinoatrial node. As a result, the heart rate declines (Fig. 5). This autonomic neural input predominates during sleep and other sedentary states, eliciting an increase in cardiac cycle time and therefore enabling the heart to expend less energy (2). In addition to decreasing the slope of the pacemaker potential, parasympa-thetic stimulation may also induce a so-called pacemaker shift (5); true pacemaker cells can become more inhibited than the latent pacemakers, thus shifting the initiations of spontaneous depolarizations from the true pacemakers to the latent ones (5).
Conduction velocity is the measure of the spread of action potentials through the heart. Parasympathetic stimulation above normal tonic activity slows this conduction velocity, and this response is termed negative dromotropic effect. It follows that an increase in conduction velocity commonly accompanying sympathetic stimulation has a positive dromo-tropic effect. The atrioventricular node is the location within the heart where conduction speed variation is most notable. Refer to Chapter 9 for more details on specific mechanisms of cardiac pacemaker mechanisms.
Fig. 7. Effect of increased sympathetic stimulation on stroke volume (see text for details).
Ventricular End-Diastolic Volume (mL)
Fig. 7. Effect of increased sympathetic stimulation on stroke volume (see text for details).
The control mechanisms of heart rate may also be dependent on gender (12). Women have been shown to exhibit higher resting frequencies of parasympathetic input than men of similar age, possibly indicating a more dominant control of heart rate via vagal stimulation than their male counterparts (12).
Like heart rate, the amount of blood ejected from the ventricles during systole is greater when the heart is modulated by an increased sympathetic input (Fig. 6). The underlying mechanism for this increased stroke volume is enhanced cardiac myocyte contractility, and the magnitude of this response is strongly affected by preload and afterload conditions, as predicted by the Frank-Starling law (6). Such an increase in contractility is characterized as a positive inotropic effect. Myocytes usually increase in length in proportion to their preload, and because they become more elongated, they also have the capability to shorten over this greater distance. This increased amount of shortening leads to an enhanced strength of contraction of the heart. As described previously, sympathetic excitation facilitates a larger and more rapid Ca+2 influx into cardiac cells, which further augments the degree of overall contraction during systole (11).
Combined with a larger preload, the increased contractility due to calcium ion influx will raise the stroke volume of the heart (Fig. 7). Such an increase in stroke volume results in a larger ejection fraction of blood from the chambers of the heart. (2). However, stroke volume is also dependent on afterload created by the relative diameter of the peripheral arteries, and will not increase as significantly under sympathetic stimulation if the afterload is elevated.
As expected from the often-antagonistic nature of the auto-nomic nervous system, parasympathetic stimulation decreases contractility. However, the relative decrease in contractility is much less significant than the increase in this parameter that sympathetic input provides (2).
An important concept to note involves simultaneous increases in heart rate and stroke volume: because cardiac output is the product of these two quantities, its overall value commonly increases with sympathetic stimulation. Conversely, cardiac output normally decreases with a higher rate of parasympa-thetic input. This is common when the body is in a sedentary state; hence, tissue oxygen and metabolite requirements are not as high.
The time necessary for the heart to contract and relax fully decreases under sympathetic stimulation, due primarily to the larger proportion of the cardiac cycle that is made available for filling. Although an increase in heart rate makes the total duration of the cardiac cycle shorter (2), the corresponding rise in contractility causes the muscular contractions to commence more rapidly and with greater force than under resting conditions. This translates to a decrease in the amount of time necessary for contraction of the heart during a complete cardiac cycle. Thus, the heart is relaxed for a greater portion of the cycle, enabling enhanced filling of the chambers to provide a greater volume of blood ejected for each contraction.
Arterial pressure, or afterload, is regulated in the short term by baroreceptors that are primarily located in the walls of the aorta and carotid arteries. In particular, baroreceptors sense both magnitude and rate of stretch of arterial walls because of pressure fluctuations within the vessels (6). The afferent fibers projecting from the baroreceptors convey this information concerning pressure shifts to the autonomic nervous system, which in turn responds by either increasing or decreasing sympathetic or parasympathetic drive. A basal tonic activity can be identified from the receptors; this activity progresses to the higher cardiovascular centers. The frequency of impulses can increase or decrease in response to these pressure changes. Decreased arterial dilation causes sympathetic nerves to increase their discharge rate and escalate the release of norepinephrine, thus increasing heart rate, stroke volume, and peripheral resistance (2).
The baroreceptor reflex functions as a negative-feedback system (6), such that a decrease in arterial stretch will induce an increased sympathetic discharge, accordingly raising cardiac output. This in turn will increase blood delivered to the vessels containing baroreceptors, increase pressure, and decrease the tonic activity of these receptors. Homeostatic control of arterial pressure is thus administered because the decreased barorecep-tor discharge rate will cause a lowered degree of sympathetic activity and revert the cardiac output back toward its basal value. In other words, the response of the baroreceptors ultimately removes the stimulus causing the initial response (6).
Importantly, long-term pressure regulation is not accomplished via baroreceptor input because of their adaptive nature (accommodation). That is, if pressure in the aorta and carotid arteries remains elevated for sustained periods, the tonic firing rates will eventually return toward resting values regardless of whether the pressures remain elevated. Long-term regulation of pressure involves numerous complex hormonal mechanisms, which are extensively influenced by the hypothalamic and medullary cardiovascular centers.
Because the heart is responsible for delivery of blood to every part of the body, homeostatic control often involves changing the amount of blood provided by the circulatory system to a given tissue, organ, or organ system. For example, the gastrointestinal system at rest normally receives approx 20% of the blood pumped by the heart during each cardiac cycle. However, during times of intense stress or exertion, the blood provided to this area may drastically decrease, while the proportion of blood provided to the heart and skeletal muscles may increase notably. Such changes in blood supply are commonly mediated by changes in resistance of the peripheral vas-culature.
At rest, the smooth muscle cells in the walls of arterioles throughout the body remain slightly contracted because of a combination of influences from the central nervous system, hormonal distribution within the vasculature, or localized organ effects. The relative degree of contraction within the arterioles is referred to as their basal tone. The stretching of the arterioles due to pulsatile blood pressure is thought to be the cause of the constant state of stress within such vessels (6). Arterioles innervated by sympathetic fibers possess an increased contractile tone, termed the neurogenic tone, because of the sustained activation of these fibers.
Control of the vascular peripheral resistance is achieved by varying the firing frequency within these sympathetic fibers. More specifically, postganglionic fibers release the neurotransmitter norepinephrine, which binds to aradrenergic receptors within the smooth muscle cells in arteriolar walls. Thus, an increase in the firing activity of these neurons produces an increase in norepinephrine levels, which in turn binds with more arreceptors and causes an overall decrease in the diameters of arterioles. In contrast, a lowering of the basal tonic activity causes vasodilation since less neurotransmitter is available for binding, causing the smooth muscle cells to relax.
The relative firing rates of arteriolar sympathetic neurons innervating a given tissue are also modulated by the need for blood elsewhere in the body. For example, if a hemorrhage occurs in the abdomen and results in significant bleeding, sympathetic activity to that area will increase, causing less blood to flow to these damaged tissues in an attempt to preserve adequate levels of flow to the heart and brain. It should be noted that other regulators exist for the control of vasomotion and the tonic activity of the sympathetic system. Local increases in extracellular cation concentrations, acetylcholine levels, and even norepinephrine itself can act to prevent extreme vasoconstriction. Adrenergic receptors that are pharmacologically different from those in smooth muscle cells (6) have been identified on postganglionic sympathetic neurons themselves and are given an a2 designation. These receptors bind with the neu-rotransmitter and inhibit its release if the amount previously liberated is excessive (negative feedback).
Blood flow through the coronary arterioles is primarily regulated by local metabolic controls that are highly coupled with myocardial oxygen consumption. That is, subtle increases in oxygen consumption by the heart will result in an increase in blood flow through the coronaries. Elevated sympathetic activity of the systemic vasculature typically induces a subsequent decrease in the diameter of the peripheral arteries. However, during sympathetic excitation, vasodilation predominates in the coronary arterioles instead of vasoconstriction; this is because oxygen consumption is raised significantly by concurrently inducing higher heart rates and levels of contractility. The factors motivating metabolic regulation therefore outweigh the vasoconstrictive effects of sympathetic innervation of the coronaries.
Blood flow to skeletal muscle is controlled in a manner similar to that for the coronary arteries in that local meta bolic factors play a vital role in regulating vessel resistance. Although increased sympathetic activity may decrease the blood flow to a resting skeletal muscle by a factor of four (6), a muscle undergoing exercise (and thus in the presence of elevated sympathetic activity) can elicit an increase in blood flow almost 20 times that of normal resting values (6). However, this muscle response must occur in conjunction with a drastic decrease in the blood flow within other tissues or organs, such as those of the abdominal cavity or nonexercis-ing muscles. This course of action allows the total peripheral resistance to remain at a functional level. Homeostatic control during exercise also exists at the skin. To cool the body from the increased metabolic heat production, sweat glands become active, and blood flow increases significantly over the normal resting value to dissipate excess body heat. The active vaso-dilation is the result of metabolic activity overcoming the increased sympathetic outflow to skin arterioles.
During the digestion of food, increased blood flow occurs in the stomach and intestines. Parasympathetic discharge to the heart increases, and sympathetic stimulus declines, lowering the heart rate. This concentration of blood to the abdominal organs facilitates the movement of nutrients to areas of the body in need and is a good example of how both branches of the autonomic nervous system work together to sustain a level of balance throughout the entire body.
The suprarenal glands can also contribute to vasomotion. Because norepinephrine is released directly into the bloodstream from these endocrine glands, arteriolar constriction in the systemic organs can result. The human "fight-or-flight" response elicited under stressful or exciting circumstances originates within the hypothalamus and via hormones travels to the pituitary gland and later the adrenal cortex, where the agent cortisol is released into the bloodstream and adrenal medulla. It is in the medulla that cortisol activates the enzyme necessary to convert norepinephrine to epinephrine, which is released into the bloodstream to amplify increased sympathetic activity (2,3). Blood flow to the skin and other internal organs (like the stomach and intestines) is greatly decreased by increasing sympathetic (and decreasing parasympathetic) tonic activity; flow to skeletal muscles and the heart increases considerably. This process can be thought of as simply delivering blood to the areas of the body most in need to deal with the demanding circumstances. The direct release of these agents into the bloodstream allows for their rapid circulation, which helps contract arterioles along with conventional sympathetic outflow. The so-called "adrenaline rush" experienced during periods of great tension or exhilaration comes from the adrenal glands.
Regulation of the veins and venules in the body is carried out by many of the same mechanisms as that for arterioles. Although veins have smooth muscle in their walls complete with aj-receptors that respond to norepinephrine, their basal tonic activity is much lower than that observed in arterioles. Thus, venules at rest can be considered to be in a more dilated state. The wall thickness of veins is also significantly less than that found in arteries, which enables the consequences of physical effects to be more prominent in veins. That is, the overall blood volume associated with veins can be greatly affected by compressive forces. For example, in skeletal muscle, the degree of muscle contraction around the vessel can push large amounts of blood back toward the heart, which enables quicker filling within the right atrium and enables sustained physical activity. If skeletal muscles surrounding veins are relaxed, the venous system can act as a blood reservoir.
Vasculature of skeletal muscles and the liver can have a unique effect on homeostasis via noninnervated a2-receptors located in arteriolar walls. Increased blood levels of epineph-rine can activate these receptors, which along with G proteins (6,11) act to catalyze an intracellular chemical reaction, resulting in decreased cytoplasmic levels of Ca2+ and a hyper-polarization of the cellular membrane. This in turn decreases the contractile machinery sensitivity to Ca2+, causing vasodilation (6). Vasodilation in the presence of epinephrine is in contrast to the decrease in vessel diameter caused by the chemically similar compound norepinephrine. The a2-receptors are more sensitive to epinephrine than aj-receptors (6). Thus, a small elevation in the concentration of epinephrine in the bloodstream (possibly provided by the adrenal medulla) can cause vasodilation. However, if the level of catecholamine increases, the more numerous aj-receptors will be activated and cause vasoconstriction. It is important to note that there is no neural input to a2-receptors, and norepinephrine therefore has no effect on their activation.
It can be seen that the parasympathetic and sympathetic effects of the heart and vasculature often elicit opposite physiological responses, yet work in conjunction to maintain homeo-stasis.
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