Guyton and Hall Physiology - Nervous Regulation of the Circulation PDF

CHAPTER 18 UNIT IV Nervous Regulation of the Circulation and Rapid Control of Arterial Pressure...

CHAPTER 18 UNIT IV Nervous Regulation of the Circulation and Rapid Control of Arterial Pressure Sympathetic Innervation of the Blood Vessels. NERVOUS REGULATION OF THE Figure 18-2 shows the distribution of sympathetic nerve CIRCULATION fibers to the blood vessels, demonstrating that in most tis- As discussed in Chapter 17, adjustment of blood flow in sues, all the vessels except the capillaries are innervated. the tissues and organs of the body is mainly the function Precapillary sphincters and metarterioles are innervated of local tissue control mechanisms. In this chapter, we in some tissues, such as the mesenteric blood vessels, discuss how nervous control of the circulation has more although their sympathetic innervation is usually not as global functions, such as redistributing blood flow to dif- dense as in the small arteries, arterioles, and veins. ferent areas of the body, increasing or decreasing pump- The innervation of the small arteries and arterioles ing activity by the heart, and providing rapid control of allows sympathetic stimulation to increase resistance to systemic arterial pressure. blood flow and thereby decrease the rate of blood flow The nervous system controls the circulation almost through the tissues. entirely through the autonomic nervous system. The total The innervation of the large vessels, particularly of function of this system is presented in Chapter 61, and the veins, makes it possible for sympathetic stimulation this subject was also introduced in Chapter 17. In this to decrease the volume of these vessels. This decrease in chapter, we consider additional specific anatomical and volume can push blood into the heart and thereby plays a functional characteristics. major role in regulation of heart pumping, as we explain later in this and subsequent chapters. AUTONOMIC NERVOUS SYSTEM Sympathetic Stimulation Increases Heart Rate and The most important part of the autonomic nervous sys- Contractility. Sympathetic fibers also go directly to the tem for regulating the circulation is the sympathetic heart, as shown in Figure 18-1. As discussed in Chapter nervous system. The parasympathetic nervous system, 9, sympathetic stimulation markedly increases the activity however, contributes importantly to regulation of heart of the heart, both increasing the heart rate and enhancing function, as described later in the chapter. its strength and volume of pumping. Sympathetic Nervous System. Figure 18-1 shows the Parasympathetic Stimulation Decreases Heart Rate anatomy of sympathetic nervous control of the circulation. and Contractility. Although the parasympathetic nerv- Sympathetic vasomotor nerve fibers leave the spinal cord ous system is exceedingly important for many other au- through all the thoracic spinal nerves and through the first tonomic functions of the body, such as control of mul- one or two lumbar spinal nerves. They then pass immedi- tiple gastrointestinal actions, it plays only a minor role ately into a sympathetic chain, one of which lies on each in regulating vascular function in most tissues. Its most side of the vertebral column. Next, they pass by two routes important circulatory effect is to control heart rate by way to the circulation: (1) through specific sympathetic nerves of parasympathetic nerve fibers to the heart in the vagus that innervate mainly the vasculature of the internal vis- nerves, shown in Figure 18-1 by the dashed red line from cera and the heart, as shown on the right side of Figure the brain medulla directly to the heart. 18-1; and (2) almost immediately into peripheral portions The effects of parasympathetic stimulation on heart of the spinal nerves distributed to the vasculature of the function were discussed in detail in Chapter 9. Prin- peripheral areas. The precise pathways of these fibers in cipally, parasympathetic stimulation causes a marked the spinal cord and in the sympathetic chains are discussed decrease in heart rate and a slight decrease in heart mus- in Chapter 61. cle contractility. 217 UNIT IV The Circulation Arteries Arterioles Sympathetic Vasoconstrictor vasoconstriction Cardioinhibitor Capillaries Vasodilator Veins Venules Figure 18-2. Sympathetic innervation of the systemic circulation. Vasomotor center Motor Reticular Cingulate gyrus substance Mesencephalon Blood Orbital vessels Sympathetic chain Vagus Heart Temporal Pons Medulla VASOMOTOR VASODILATOR CENTER VASOCONSTRICTOR Blood Figure 18-3. Areas of the brain that play important roles in the nerv- vessels ous regulation of the circulation. The dashed lines represent inhibi- tory pathways. but is much less potent in skeletal muscle, heart, and the brain. Vasomotor Center in the Brain and Its Control of the Vasoconstrictor System. Located bilaterally mainly in the reticular substance of the medulla and lower third of Figure 18-1. Anatomy of sympathetic nervous control of the circula- the pons is an area called the vasomotor center, shown in tion. Also, shown by the dashed red line, is a vagus nerve that carries Figure 18-1 and Figure 18-3. This center transmits par- parasympathetic signals to the heart. asympathetic impulses through the vagus nerves to the heart and sympathetic impulses through the spinal cord Sympathetic Vasoconstrictor System and and peripheral sympathetic nerves to virtually all arteries, Its Control by the Central Nervous System arterioles, and veins of the body. The sympathetic nerves carry large numbers of vasocon- Although the total organization of the vasomotor cen- strictor nerve fibers and only a few vasodilator fibers. The ter is still unclear, experiments have made it possible to vasoconstrictor fibers are distributed to essentially all seg- identify certain important areas in this center: ments of the circulation, but more to some tissues than 1. A vasoconstrictor area located bilaterally in the an- to others. This sympathetic vasoconstrictor effect is espe- terolateral portions of the upper medulla. The neu- cially powerful in the kidneys, intestines, spleen, and skin rons originating in this area distribute their fibers 218  Chapter 18 Nervous Regulation of the Circulation and Rapid Control of Arterial Pressure tone throughout the body. A few minutes later, a small Arterial pressure (mm Hg) 150 amount of the hormone norepinephrine was injected into Total spinal the blood (norepinephrine is the principal vasoconstrictor 125 hormonal substance secreted at the endings of the sympa- anesthesia 100 thetic vasoconstrictor nerve fibers). As this injected hor- UNIT IV mone was transported in the blood to blood vessels, the 75 vessels once again became constricted, and the arterial pressure rose to a level even greater than normal for 1 to 3 50 minutes until the norepinephrine was destroyed. 25 Injection of norepinephrine Control of Heart Activity by the Vasomotor Center. 0 At the same time that the vasomotor center regulates the 0 5 10 15 20 25 amount of vascular constriction, it also controls heart ac- Minutes tivity. The lateral portions of the vasomotor center trans- Figure 18-4. Effect of total spinal anesthesia on the arterial pres- mit excitatory impulses through the sympathetic nerve sure, showing a marked decrease in pressure resulting from loss of fibers to the heart when there is a need to increase heart vasomotor tone. rate and contractility. Conversely, when there is a need to decrease heart pumping, the medial portion of the vaso- to all levels of the spinal cord, where they excite motor center sends signals to the adjacent dorsal motor preganglionic vasoconstrictor neurons of the sym- nuclei of the vagus nerves, which then transmit parasym- pathetic nervous system. pathetic impulses through the vagus nerves to the heart to 2. A vasodilator area located bilaterally in the ante- decrease heart rate and heart contractility. Therefore, the rolateral portions of the lower half of the medulla. vasomotor center can increase or decrease heart activity. The fibers from these neurons project upward to Heart rate and the strength of heart contractions ordinar- the vasoconstrictor area just described, inhibiting ily increase when vasoconstriction occurs and ordinarily the vasoconstrictor activity of this area and causing decrease when vasoconstriction is inhibited. vasodilation. 3. A sensory area located bilaterally in the nucleus Control of the Vasomotor Center by Higher Nervous tractus solitarius in the posterolateral portions of Centers. Large numbers of small neurons located through- the medulla and lower pons. The neurons of this out the reticular substance of the pons, mesencephalon, area receive sensory nerve signals from the circu- and diencephalon can excite or inhibit the vasomotor latory system mainly through the vagus and glos- center. This reticular substance is shown in Figure 18-3. In sopharyngeal nerves, and output signals from this general, the neurons in the more lateral and superior por- sensory area then help control activities of the vaso- tions of the reticular substance cause excitation, whereas constrictor and vasodilator areas of the vasomotor the more medial and inferior portions cause inhibition. center, thus providing reflex control of many circu- The hypothalamus plays a special role in controlling latory functions. An example is the baroreceptor re- the vasoconstrictor system because it can exert powerful flex for controlling arterial pressure, described later excitatory or inhibitory effects on the vasomotor center. in this chapter. The posterolateral portions of the hypothalamus cause mainly excitation, whereas the anterior portion can cause Continuous Partial Constriction of Blood Vessels by mild excitation or inhibition, depending on the precise Sympathetic Vasoconstrictor Tone. Under normal con- part of the anterior hypothalamus that is stimulated. ditions, the vasoconstrictor area of the vasomotor center Many parts of the cerebral cortex can also excite or transmits signals continuously to the sympathetic vaso- inhibit the vasomotor center. Stimulation of the motor constrictor nerve fibers over the entire body, causing slow cortex, for example, excites the vasomotor center because firing of these fibers at a rate of about 0.5 to 2 impulses of impulses transmitted downward into the hypothala- per second. This continual firing is called sympathetic mus and then to the vasomotor center. Also, stimulation vasoconstrictor tone. These impulses normally maintain of the anterior temporal lobe, orbital areas of the frontal a partial state of constriction in the blood vessels, called cortex, anterior part of the cingulate gyrus, amygdala, sep- vasomotor tone. tum, and hippocampus can all excite or inhibit the vaso- Figure 18-4 demonstrates the significance of vaso- motor center, depending on the precise portions of these constrictor tone. In the experiment shown in this figure, areas that are stimulated and the intensity of the stimulus. a spinal anesthetic was administered to an animal. This Thus, widespread basal areas of the brain can have pro- anesthetic blocked all transmission of sympathetic nerve found effects on cardiovascular function. impulses from the spinal cord to the periphery. As a result, the arterial pressure fell from 100 to 50 mm Hg, Norepinephrine Is the Sympathetic Vasoconstrictor demonstrating the effect of the loss of vasoconstrictor Neurotransmitter. The substance secreted at the endings 219 UNIT IV The Circulation of the vasoconstrictor nerves is almost entirely norepi- Role of the Nervous System in Rapid nephrine, which acts directly on the alpha-adrenergic Control of Arterial Pressure receptors of the vascular smooth muscle to cause vaso- One of the most important functions of nervous control constriction, as discussed in Chapter 61. of the circulation is its capability to cause rapid increases in arterial pressure. For this purpose, the entire vaso- Adrenal Medullae and Their Relationship to the Sym- constrictor and cardioaccelerator functions of the sym- pathetic Vasoconstrictor System. Sympathetic impulses pathetic nervous system are stimulated together. At the are transmitted to the adrenal medullae at the same time same time, there is reciprocal inhibition of parasympa- that they are transmitted to the blood vessels. These im- thetic vagal inhibitory signals to the heart. Thus, the fol- pulses cause the medullae to secrete epinephrine and nor- lowing three major changes occur simultaneously, each of epinephrine into the circulating blood. These two hormones which helps increase arterial pressure: are carried in the blood stream to all parts of the body, 1. Most arterioles of the systemic circulation are con- where they act directly on all blood vessels and usually stricted, which greatly increases the total peripheral cause vasoconstriction. In a few tissues, epinephrine causes resistance, thereby increasing the arterial pressure. vasodilation because it also stimulates beta-adrenergic re- 2. The veins especially (but the other large vessels of ceptors, which dilates rather than constricts certain vessels, the circulation as well) are strongly constricted. This as discussed in Chapter 61. constriction displaces blood out of the large periph- eral blood vessels toward the heart, thus increasing Sympathetic Vasodilator System and Its Control by the the volume of blood in the heart chambers. The Central Nervous System. The sympathetic nerves to skel- stretch of the heart then causes the heart to beat etal muscles carry sympathetic vasodilator fibers, as well as with greater force and therefore to pump increased constrictor fibers. In some animals, such as the cat, these quantities of blood. This also increases the arterial dilator fibers release acetylcholine, not norepinephrine, at pressure. their endings. However, in primates, the vasodilator effect 3. Finally, the heart is directly stimulated by the au- is believed to be caused by epinephrine exciting specific tonomic nervous system, further enhancing cardiac beta-adrenergic receptors in the muscle vasculature. The pathway for central nervous system (CNS) control pumping. Much of this enhanced cardiac pumping is of the vasodilator system is shown by the dashed lines in caused by an increase in the heart rate, which some- Figure 18-3. The principal area of the brain controlling this times increases to as much as three times normal. system is the anterior hypothalamus. In addition, sympathetic nervous signals directly Possible Role of the Sympathetic Vasodilator System. increase the contractile force of the heart muscle, The sympathetic vasodilator system does not appear to play increasing the capability of the heart to pump larger a major role in the control of the circulation in humans be- volumes of blood. During strong sympathetic stimu- cause complete block of the sympathetic nerves to the mus- lation, the heart can pump about two times as much cles hardly affects the ability of these muscles to control their blood as under normal conditions, which contrib- own blood flow in many physiological conditions. Yet, some utes still more to the acute rise in arterial pressure. experiments have suggested that at the onset of exercise, the sympathetic system might cause initial vasodilation in skel- Nervous Control of Arterial Pressure Is Rapid. An es- etal muscles to allow an anticipatory increase in blood flow, pecially important characteristic of nervous control of ar- even before the muscles require increased nutrients. There terial pressure is its rapidity of response, beginning within is evidence in humans that this sympathetic vasodilator re- seconds and often increasing the pressure to two times sponse in skeletal muscles may be mediated by circulating normal within 5 to 10 seconds. Conversely, sudden inhi- epinephrine, which stimulates beta-adrenergic receptors, or bition of nervous cardiovascular stimulation can decrease by nitric oxide released from the vascular endothelium in re- sponse to stimulation by acetylcholine. the arterial pressure to as little as half-normal within 10 to Emotional Fainting—Vasovagal Syncope. An interest- 40 seconds. Therefore, nervous control is the most rapid ing vasodilatory reaction occurs in people who experience mechanism for arterial pressure regulation. intense emotional disturbances that cause fainting. In this case, the muscle vasodilator system becomes activated INCREASES IN ARTERIAL PRESSURE and, at the same time, the vagal cardioinhibitory center DURING MUSCLE EXERCISE AND OTHER transmits strong signals to the heart to slow the heart rate STRESSES markedly. The arterial pressure falls rapidly, which reduces blood flow to the brain and causes the person to lose con- An important example of the nervous system’s ability sciousness. This overall effect is called vasovagal syncope. to increase arterial pressure is the rise in pressure that Emotional fainting begins with disturbing thoughts in the occurs during muscle exercise. During heavy exercise, the cerebral cortex. The pathway probably then goes to the vas- muscles require greatly increased blood flow. Part of this odilatory center of the anterior hypothalamus next to the increase results from local vasodilation of the muscle vas- vagal centers of the medulla, to the heart through the vagus culature caused by increased metabolism of the muscle nerves, and also through the spinal cord to the sympathetic cells, as explained in Chapter 17. An additional increase vasodilator nerves of the muscles. results from simultaneous elevation of arterial pressure 220  Chapter 18 Nervous Regulation of the Circulation and Rapid Control of Arterial Pressure caused by sympathetic stimulation of the overall circula- multiple subconscious special nervous control mecha- tion during exercise. In heavy exercise, the arterial pres- nisms operate all the time to maintain the arterial pressure sure rises by about 30% to 40%, which further increases at or near normal. Almost all these are negative feedback blood flow by almost 2-fold. reflex mechanisms, described in the following sections. The increase in arterial pressure during exercise results Baroreceptor Arterial Pressure Control UNIT IV mainly from effects of the nervous system. At the same time that the motor areas of the brain become activated System—Baroreceptor Reflexes to cause exercise, most of the reticular activating system The best known of the nervous mechanisms for arterial of the brain stem is also activated, which includes greatly pressure control is the baroreceptor reflex. Basically, this increased stimulation of the vasoconstrictor and cardio- reflex is initiated by stretch receptors, called baroreceptors acceleratory areas of the vasomotor center. These effects or pressoreceptors, located at specific points in the walls of rapidly increase the arterial pressure to keep pace with the several large systemic arteries. A rise in arterial pressure increase in muscle activity. stretches the baroreceptors and causes them to transmit In many other types of stress besides muscle exercise, signals into the CNS. Feedback signals are then sent back a similar rise in pressure can also occur. For example, dur- through the autonomic nervous system to the circulation ing extreme fright, the arterial pressure sometimes rises to reduce arterial pressure down toward the normal level. by as much as 75 to 100 mm Hg within a few seconds. This response is called the alarm reaction, and it provides Physiologic Anatomy of the Baroreceptors and Their an elevated arterial pressure that can immediately supply Innervation. Baroreceptors are spray-type nerve end- blood to the muscles of the body that might be needed to ings that lie in the walls of the arteries and are stimulated respond instantly to enable flight from danger. when stretched. A few baroreceptors are located in the wall of almost every large artery of the thoracic and neck regions but, as shown in Figure 18-5, baroreceptors are REFLEX MECHANISMS FOR MAINTAINING extremely abundant in the following regions: (1) the wall NORMAL ARTERIAL PRESSURE of each internal carotid artery, slightly above the carotid Aside from the exercise and stress functions of the auto- bifurcation, an area known as the carotid sinus; and (2) nomic nervous system to increase arterial pressure, the wall of the aortic arch. Glossopharyngeal nerve Glossopharyngeal nerve Hering’s nerve External carotid artery External carotid artery Internal carotid artery Internal carotid artery Carotid body Hering’s nerve Carotid sinus Common carotid artery Vagus nerve Carotid body (chemoreceptor) Carotid sinus Aortic baroreceptors Common carotid artery Figure 18-5. Baroreceptor system for controlling arterial pressure. 221 UNIT IV The Circulation Number of impulses from carotid Arterial pressure (mm Hg) sinus nerves per second 150 100 ΔI = maximum ΔP Both common Carotids released carotids clamped 50 0 0 80 160 240 0 2 4 6 8 10 12 14 Arterial blood pressure (mm Hg) Minutes Figure 18-6. Activation of the baroreceptors at different levels of ar- Figure 18-7. Typical carotid sinus reflex effect on aortic arterial pres- terial pressure. ΔI, Change in carotid sinus nerve impulses per second; sure caused by clamping both common carotids (after the two vagus ΔP, change in arterial blood pressure (in mm Hg). nerves have been cut). Figure 18-5 shows that signals from the carotid baro- the vasoconstrictor center of the medulla and excite the va- receptors are transmitted through small Hering’s nerves to gal parasympathetic center. The net effects are as follows: the glossopharyngeal nerves in the high neck and then to (1) vasodilation of the veins and arterioles throughout the nucleus tractus solitarius in the medullary area of the the peripheral circulatory system; and (2) decreased heart brain stem. Signals from the aortic baroreceptors in the rate and strength of heart contraction. Therefore, excita- arch of the aorta are transmitted through the vagus nerves tion of the baroreceptors by high pressure in the arteries to the same nucleus tractus solitarius of the medulla. reflexly causes the arterial pressure to decrease because of a decrease in peripheral resistance and a decrease in Response of the Baroreceptors to Changes in Arte- cardiac output. Conversely, low pressure has the opposite rial Pressure. Figure 18-6 shows the effects of different effects, reflexly causing the pressure to rise back toward arterial pressure levels on the rate of impulse transmission normal. in a Hering’s carotid sinus nerve. Note that the carotid Figure 18-7 shows a typical reflex change in arterial sinus baroreceptors are not stimulated at all by pressures pressure caused by occluding the two common carotid between 0 and 50 to 60 mm Hg but, above these levels, arteries. This reduces the carotid sinus pressure; as a they respond progressively more rapidly and reach a max- result, signals from the baroreceptors decrease and imum at about 180 mm Hg. The responses of the aortic cause less inhibitory effect on the vasomotor center. The baroreceptors are similar to those of the carotid receptors vasomotor center then becomes much more active than except that they operate, in general, at arterial pressure usual, causing the aortic arterial pressure to rise and levels about 30 mm Hg higher. remain elevated during the 10 minutes that the carot- Note especially that in the normal operating range of ids are occluded. Removal of the occlusion allows the arterial pressure, around 100 mm Hg, even a slight change pressure in the carotid sinuses to rise, and the carotid in pressure causes a strong change in the baroreflex signal sinus reflex now causes the aortic pressure to fall almost to readjust arterial pressure back toward normal. Thus, immediately to slightly below normal as a momentary the baroreceptor feedback mechanism functions most overcompensation and then return to normal in another effectively in the pressure range where it is most needed. minute. The baroreceptors respond rapidly to changes in arte- rial pressure; the rate of impulse firing increases in the Baroreceptors Attenuate Blood Pressure Changes fraction of a second during each systole and decreases During Changes in Body Posture. The ability of the ba- again during diastole. Furthermore, the baroreceptors roreceptors to maintain relatively constant arterial pres- respond much more to a rapidly changing pressure than to sure in the upper body is important when a person stands a stationary pressure. That is, if the mean arterial pressure up after lying down. Immediately on standing, the arterial is 150 mm Hg but at that moment is rising rapidly, the pressure in the head and upper part of the body tends to rate of impulse transmission may be as much as twice that fall, and marked reduction of this pressure could cause when the pressure is stationary at 150 mm Hg. loss of consciousness. However, the falling pressure at the baroreceptors elicits an immediate reflex, resulting in Circulatory Reflex Initiated by the Baroreceptors. strong sympathetic discharge throughout the body that After the baroreceptor signals have entered the nucleus minimizes the decrease in pressure in the head and up- tractus solitarius of the medulla, secondary signals inhibit per body. 222  Chapter 18 Nervous Regulation of the Circulation and Rapid Control of Arterial Pressure Normal 200 6 Percentage of occurrence 5 Normal UNIT IV 100 4 3 Arterial pressure (mm Hg) 0 2 24 1 Denervated Baroreceptors denervated 200 0 0 50 100 150 200 250 Mean arterial pressure (mm Hg) Figure 18-9. Frequency distribution curves of the arterial pressure 100 for a 24-hour period in a normal dog and in the same dog several weeks after the baroreceptors had been denervated. (Modified from Cowley AW Jr, Liard JP, Guyton AC: Role of baroreceptor reflex in daily control of arterial blood pressure and other variables in dogs. Circ Res 32:564, 1973.) 0 Time (min) A primary purpose of the arterial baroreceptor system 24 is therefore to reduce the minute by minute variation in Figure 18-8. Two-hour records of arterial pressure in a normal dog arterial pressure to about one-third that which would (top) and in the same dog (bottom) several weeks after the barore- occur if the baroreceptor system were not present. ceptors had been denervated. (Modified from Cowley AW Jr, Liard JF, Guyton AC: Role of baroreceptor reflex in daily control of arterial blood pressure and other variables in dogs. Circ Res 32:564, 1973.) Are the Baroreceptors Important in Long-Term Regulation of Arterial Pressure? Although the arte- Pressure Buffer Function of the Baroreceptor Control rial baroreceptors provide powerful moment to moment System. Because the baroreceptor system opposes in- control of arterial pressure, their importance in long-term creases or decreases in arterial pressure, it is called a pres- blood pressure regulation has been controversial. One rea- sure buffer system, and the nerves from the baroreceptors son that the baroreceptors have been considered by some are called buffer nerves. physiologists to be relatively unimportant in chronic regula- Figure 18-8 shows the importance of this buffer func- tion of arterial pressure is that they tend to reset in 1 to 2 tion of the baroreceptors. The upper panel in this figure days to the pressure level to which they are exposed. That shows an arterial pressure recording for 2 hours from a is, if the arterial pressure rises from the normal value of 100 normal dog, and the lower panel shows an arterial pres- to 160 mm Hg, a very high rate of baroreceptor impulses is sure recording from a dog whose baroreceptor nerves at first transmitted. During the next few minutes, the rate from the carotid sinuses and the aorta had been removed. of firing diminishes considerably. Then, it diminishes much Note the extreme variability of pressure in the denervated more slowly during the next 1 to 2 days, at the end of which dog caused by simple events of the day, such as lying down, time the rate of firing will have returned to nearly normal, standing, excitement, eating, defecation, and noises. despite the fact that the mean arterial pressure still remains Figure 18-9 shows the frequency distributions of the at 160 mm Hg. Conversely, when the arterial pressure falls mean arterial pressures recorded for a 24-hour day in the to a very low level, the baroreceptors at first transmit no im- normal dog and the denervated dog. Note that when the pulses but gradually, over 1 to 2 days, the rate of barorecep- baroreceptors were functioning normally, the mean arte- tor firing returns toward the control level. rial pressure remained within a narrow range of between This resetting of the baroreceptors may attenuate their 85 and 115 mm Hg throughout the day and, for most of potency as a control system for correcting disturbances the day, it remained at about 100 mm Hg. After denerva- that tend to change arterial pressure for longer than a few tion of the baroreceptors, however, the frequency distri- days at a time. Experimental studies, however, have sug- bution curve flattened, showing that the pressure range gested that the baroreceptors do not completely reset and increased 2.5-fold, frequently falling to as low as 50 mm may therefore contribute to long-term blood pressure reg- Hg or rising to more than 160 mm Hg. Thus, one can see ulation, especially by influencing sympathetic nerve activ- the extreme variability of pressure in the absence of the ity of the kidneys. For example, with prolonged increases arterial baroreceptor system. in arterial pressure, the baroreceptor reflexes may mediate 223 UNIT IV The Circulation decreases in renal sympathetic nerve activity that promote in conditions such as severe obesity and obstructive sleep increased excretion of sodium and water by the kidneys. apnea, a serious sleep disorder associated with repetitive This action, in turn, causes a gradual decrease in blood episodes of nocturnal breathing cessation and hypoxia. volume, which helps restore arterial pressure toward nor- mal. Thus, long-term regulation of mean arterial pressure Atrial and Pulmonary Artery Reflexes Regulate Arteri- by the baroreceptors requires interaction with additional al Pressure. The atria and pulmonary arteries have stretch systems, principally the renal–body fluid–pressure control receptors in their walls called low-pressure receptors. Low- system (along with its associated nervous and hormonal pressure receptors are similar to the baroreceptor stretch mechanisms), discussed in Chapters 19 and 30. receptors of the large systemic arteries. These low-pressure Experimental studies and clinical trials have shown receptors play an important role, especially in minimizing that chronic electrical stimulation of carotid sinus afferent arterial pressure changes in response to changes in blood nerve fibers can cause sustained reductions in sympathetic volume. For example, if 300 milliliters of blood suddenly nervous system activity and arterial pressure of at least 15 are infused into a dog with all receptors intact, the arte- to 20 mm Hg. These observations suggest that most, if rial pressure rises only about 15 mm Hg. With the arterial not all, the baroreceptor reflex resetting that occurs when baroreceptors denervated, the pressure rises about 40 mm increases in arterial pressure are sustained, as in chronic Hg. If the low-pressure receptors also are denervated, the hypertension, is due to resetting of the carotid sinus nerve arterial pressure rises about 100 mm Hg. mechanoreceptors themselves rather than resetting in Thus, one can see that even though the low-pressure central nervous system vasomotor centers. receptors in the pulmonary artery and in the atria cannot detect the systemic arterial pressure, they do detect simul- Control of Arterial Pressure by the Carotid and Aortic taneous increases in pressure in the low-pressure areas of Chemoreceptors—Effect of Low Oxygen on Arterial the circulation caused by increase in volume. Also, they Pressure. Closely associated with the baroreceptor pres- elicit reflexes parallel to the baroreceptor reflexes to make sure control system is a chemoreceptor reflex that operates the total reflex system more potent for control of arterial in much the same way as the baroreceptor reflex except pressure. that chemoreceptors, instead of stretch receptors, initiate the response. Atrial Reflexes That Activate the Kidneys—The The chemoreceptor cells are sensitive to low oxygen Volume Reflex. Stretch of the atria and activation of or elevated carbon dioxide and hydrogen ion levels. They low-pressure atrial receptors also causes reflex reductions are located in several small chemoreceptor organs about 2 in renal sympathetic nerve activity, decreased tubular re- millimeters in size (two carotid bodies, one of which lies absorption, and dilation of afferent arterioles in the kid- in the bifurcation of each common carotid artery, and neys (Figure 18-10). Signals are also transmitted simul- usually one to three aortic bodies adjacent to the aorta). taneously from the atria to the hypothalamus to decrease The chemoreceptors excite nerve fibers that along with secretion of antidiuretic hormone (ADH). The decreased the baroreceptor fibers, pass through Hering’s nerves and afferent arteriolar resistance in the kidneys causes the the vagus nerves into the vasomotor center of the brain glomerular capillary pressure to rise, with a resultant in- stem. crease in filtration of fluid into the kidney tubules. The de- Each carotid or aortic body is supplied with an abun- crease in ADH level diminishes the reabsorption of water dant blood flow through a small nutrient artery, so the from the tubules. The combination of these effects—an chemoreceptors are always in close contact with arterial increase in glomerular filtration and a decrease in reab- blood. Whenever the arterial pressure falls below a criti- sorption of the fluid—increases fluid loss by the kidneys cal level, the chemoreceptors become stimulated because and attenuates the increased blood volume. Atrial stretch diminished blood flow causes decreased oxygen, as well caused by increased blood volume also elicits release of as excess buildup of carbon dioxide and hydrogen ions atrial natriuretic peptide, a hormone that adds further to that are not removed by the slowly flowing blood. the excretion of sodium and water in the urine and return The signals transmitted from the chemoreceptors excite of blood volume toward normal (see Figure 18-10). the vasomotor center, and this response elevates the arte- All these mechanisms that tend to return blood volume rial pressure back toward normal. However, this chemore- back toward normal after a volume overload act indirectly ceptor reflex is not a powerful arterial pressure controller as pressure controllers, as well as blood volume control- until the arterial pressure falls below 80 mm Hg. Therefore, lers, because excess volume drives the heart to greater it is at the lower pressures that this reflex becomes impor- cardiac output and higher arterial pressure. This volume tant to help prevent further decreases in arterial pressure. reflex mechanism is discussed again in Chapter 30, along The chemoreceptors are discussed in much more detail with other mechanisms of blood volume control. in Chapter 42 in relation to respiratory control, in which they normally play a far more important role than in blood Increased Atrial Pressure Raises Heart Rate—Bainbridge pressure control. However, activation of the chemorecep- Reflex. Increases in atrial pressure sometimes increase the tors may also contribute to increases in arterial pressure heart rate as much as 75%, particularly when the prevailing 224  Chapter 18 Nervous Regulation of the Circulation and Rapid Control of Arterial Pressure Blood volume Bainbridge UNIT IV reflex Cardiac Atrial Heart output stretch rate Atrial Arterial “volume” pressure reflex Baroreceptor reflex Renal Atrial sympathetic Antidiuretic natriuretic activity hormone peptide Sodium and water Figure 18-10. Reflex responses to increased blood excretion volume which increase arterial pressure and atrial stretch. heart rate is slow. When the heart rate is rapid, atrial stretch and low-pressure receptors, all of which are located in the cause by infusion of fluids may reduce the heart rate due to peripheral circulation outside the brain. However, when activation of arterial baroreceptors. Thus, the net effect of blood flow to the vasomotor center in the lower brain increased blood volume and atrial stretch on heart rate de- stem becomes decreased severely enough to cause nutri- pends on the relative contributions of the baroreceptor re- tional deficiency—that is, to cause cerebral ischemia—the flexes (which tends to slow the heart rate) and the Bainbridge vasoconstrictor and cardioaccelerator neurons in the reflex which tends to accelerate the heart rate, as shown in vasomotor center respond directly to the ischemia and Figure 18-10. When blood volume is increased above nor- become strongly excited. When this excitation occurs, the mal, the Bainbridge reflex often increases heart rate despite systemic arterial pressure often rises to a level as high as the inhibitory actions of the baroreflexes. the heart can possibly pump. This effect is believed to be A small part of the increased heart rate associated with caused by failure of the slowly flowing blood to carry car- increased blood volume and atrial stretch is caused by a bon dioxide away from the brain stem vasomotor center. direct effect of the increased atrial volume to stretch the At low levels of blood flow to the vasomotor center, the sinus node; it was noted in Chapter 10 that such direct local concentration of carbon dioxide increases greatly stretch can increase the heart rate as much as 15%. An and has an extremely potent effect in stimulating the sym- additional 40% to 60% increase in heart rate is caused by pathetic vasomotor nervous control areas in the brain’s the Bainbridge reflex. The stretch receptors of the atria medulla. that elicit the Bainbridge reflex transmit their afferent sig- It is possible that other factors, such as buildup of lactic nals through the vagus nerves to the medulla of the brain. acid and other acidic substances in the vasomotor center, Then efferent signals are transmitted back through vagal also contribute to the marked stimulation and elevation and sympathetic nerves to increase the heart rate and in arterial pressure. This arterial pressure elevation in strength of heart contraction. Thus, this reflex helps pre- response to cerebral ischemia is known as the CNS isch- vent damming of blood in the veins, atria, and pulmonary emic response. circulation. The ischemic effect on vasomotor activity can elevate the mean arterial pressure dramatically, sometimes to as high as 250 mm Hg for as long as 10 minutes. The degree DECREASED BLOOD FLOW TO BRAIN of sympathetic vasoconstriction caused by intense cerebral VASOMOTOR CENTER ELICITS INCREASED ischemia is often so great that some of the peripheral ves- BLOOD PRESSURE—CNS ISCHEMIC sels become totally or almost totally occluded. The kidneys, RESPONSE for example, often cease their production of urine entirely Most nervous control of blood pressure is achieved by because of renal arteriolar constriction in response to reflexes that originate in the baroreceptors, chemoreceptors, the sympathetic discharge. Therefore, the CNS ischemic 225 UNIT IV The Circulation response is one of the most powerful of all the activators of venous reservoirs of the abdomen, helping translocate the sympathetic vasoconstrictor system. blood out of the abdominal vascular reservoirs toward the heart. As a result, increased quantities of blood are Importance of CNS Ischemic Response as a Regulator made available for the heart to pump. This overall re- of Arterial Pressure. Despite the powerful nature of the sponse is called the abdominal compression reflex. The CNS ischemic response, it does not become significant resulting effect on the circulation is the same as that until the arterial pressure falls far below normal, down caused by sympathetic vasoconstrictor impulses when to 60 mm Hg and below, reaching its greatest degree of they constrict the veins—an increase in both cardiac stimulation at a pressure of 15 to 20 mm Hg. Therefore, output and arterial pressure. The abdominal compres- the CNS ischemic response is not one of the normal sion reflex is probably much more important than was mechanisms for regulating arterial pressure. Instead, it realized in the past because it is well known that people operates principally as an emergency pressure control sys- whose skeletal muscles have been paralyzed are consid- tem that acts rapidly and powerfully to prevent further erably more prone to hypotensive episodes than people decrease in arterial pressure whenever blood flow to the with normal skeletal muscles. brain decreases dangerously close to the lethal level. It is sometimes called the last-ditch stand pressure control Skeletal Muscle Contraction Increases Cardiac mechanism. Output and Arterial Pressure During Exercise. When the skeletal muscles contract during exercise, Cushing Reaction to Increased Pressure Around the they compress blood vessels throughout the body. Even Brain. The Cushing reaction is a special type of CNS is- anticipation of exercise tightens the muscles, thereby chemic response that results from increased pressure of compressing the vessels in the muscles and in the ab- the cerebrospinal fluid around the brain in the cranial domen. This compression translocates blood from the vault. For example, when the cerebrospinal fluid pres- peripheral vessels into the heart and lungs and, there- sure rises to equal the arterial pressure, it compresses the fore, increases cardiac output. This effect is essential whole brain, as well as the arteries in the brain, and cuts in helping cause the fivefold to sevenfold increase in off the blood supply to the brain. This action initiates a cardiac output that sometimes occurs during heavy ex- CNS ischemic response that causes the arterial pressure ercise. The rise in cardiac output, in turn, is an essen- to rise. When the arterial pressure has risen to a level tial ingredient in increasing the arterial pressure during higher than the cerebrospinal fluid pressure, blood will exercise, from a normal mean of 100 mm Hg up to 130 flow once again into the vessels of the brain to relieve the to 160 mm Hg. brain ischemia. Ordinarily, the blood pressure reaches a new equilibrium level slightly higher than the cerebrospi- RESPIRATORY WAVES IN THE ARTERIAL nal fluid pressure, thus allowing blood to begin to flow PRESSURE through the brain again. The Cushing reaction helps pro- tect vital centers of the brain from loss of nutrition if the With each cycle of respiration, the arterial pressure usu- cerebrospinal fluid pressure ever rises high enough to ally rises and falls 4 to 6 mm Hg in a wavelike manner, compress the cerebral arteries. causing respiratory waves in the arterial pressure. The waves result from several different effects, some of which are reflex in nature, as follows: SPECIAL FEATURES OF NERVOUS 1. Many of the breathing signals that arise in the res- CONTROL OF ARTERIAL PRESSURE piratory center of the medulla spill over into the vasomotor center with each respiratory cycle. ROLE OF THE SKELETAL NERVES AND 2. Every time a person inspires, the pressure in the SKELETAL MUSCLES IN INCREASING thoracic cavity becomes more negative than usual, CARDIAC OUTPUT AND ARTERIAL causing the blood vessels in the chest to expand. PRESSURE This reduces the quantity of blood returning to the Although most rapidly acting nervous control of the circu- left side of the heart and thereby momentarily de- lation is affected through the autonomic nervous system, at creases the cardiac output and arterial pressure. least two conditions exist in which the skeletal nerves and 3. The pressure changes caused in the thoracic vessels muscles also play major roles in circulatory responses. by respiration can excite vascular and atrial stretch receptors. Abdominal Compression Reflex Increases Cardiac Although it is difficult to analyze the exact relations of Output and Arterial Pressure. When a baroreceptor all these factors in causing the respiratory pressure waves, or chemoreceptor reflex is elicited, nerve signals are the net result during normal respiration is usually an transmitted simultaneously through skeletal nerves to increase in arterial pressure during the early part of expi- skeletal muscles of the body, particularly to the abdomi- ration and a decrease in pressure during the remainder of nal muscles. Muscle contraction then compresses all the the respiratory cycle. During deep respiration, the blood 226  Chapter 18 Nervous Regulation of the Circulation and Rapid Control of Arterial Pressure Pressure (mm Hg) pressure can rise and fall as much as 20 mm Hg with each 200 100 respiratory cycle. 160 120 60 Arterial Pressure Vasomotor Waves— 80 Oscillation of Pressure Reflex Control 40 Systems 0 UNIT IV Often while recording arterial pressure, in addition to the A B small pressure waves caused by respiration, some much Figure 18-11. A, Vasomotor waves caused by oscillation of the CNS larger waves are also noted—as high as 10 to 40 mm Hg ischemic response. B, Vasomotor waves caused by baroreceptor re- at times—that rise and fall more slowly than the respi- flex oscillation. ratory waves. The duration of each cycle varies from 26 seconds in the anesthetized dog to 7 to 10 seconds in the cally as long as the cerebrospinal fluid pressure remained unanesthetized human. These waves are called vasomo- elevated. tor waves or Mayer waves. Such records are illustrated in Thus, any reflex pressure control mechanism can oscil- Figure 18-11, showing the cyclical rise and fall in arterial late if the intensity of feedback is strong enough, and if there pressure. is a delay between excitation of the pressure receptor and the The cause of vasomotor waves is reflex oscillation of subsequent pressure response. The vasomotor waves illus- one or more nervous pressure control mechanisms, some trate that the nervous reflexes that control arterial pressure of which are the following. obey the same principles as those applicable to mechanical and electrical control systems. For example, if the feedback Oscillation of Baroreceptor and Chemoreceptor gain is too great in the guiding mechanism of an automatic Reflexes. The vasomotor waves of Figure 18-11B are pilot for an airplane, and there is also delay in the response often seen in experimental pressure recordings, al- time of the guiding mechanism, the plane will oscillate from though they are usually much less intense than shown side to side instead of following a straight course. in the figure. They are caused mainly by oscillation of the baroreceptor reflex. That is, a high pressure excites the baroreceptors, which then inhibits the sympathetic Bibliography nervous system and lowers the pressure a few seconds Cowley AW Jr: Long-term control of arterial blood pressure. Physiol later. The decreased pressure, in turn, reduces the ba- Rev 72:231, 1992. roreceptor stimulation and allows the vasomotor cent- Dampney RA: Central neural control of the cardiovascular system: er to become active once again, elevating the pressure current perspectives. Adv Physiol Educ 40:283, 2016. to a high value. 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