Lecture 8 – Cardiovascular Regulation Cardiovascular Regulation (Slide 1) 1. Remote CNS control of blood pressure 2. Local VMS control of blood flow 3. Baroreceptor reflexes Baroreceptor Control Of Arterial Pressure In Mammals (Slide 2) 1. Start with an increase in systemic mean arterial pressure. Through the diagram, you have a reflex arc. 2. Suppose your mean arterial pressure goes from 100mmHg to 175mmHg. That change is detected by a sensory receptor, called a baroreceptor. It is a mechanoreceptor that responds to changes in pressure. 3. It sends a message to the medulla in the brainstem via an afferent pathway. In the brainstem is a central controller. The center has the ability to detect the changes and report it to other parts of the brain as an “error in pressure” because it deviates from equilibrium. 4. The information is integrated and relayed through efferent pathways out of the brain to some effector or activator. In this case, it is the heart and blood vessels. The negative signs mean the message will inhibit something. 5. This will cause the heart rate to decrease (bradycardia) and blood vessels to dilate (vasodilation). Two direct determinants of cardiac output are stroke volume and rate. If one decreases while the other is maintained, the cardiac output decreases. So because we have a decrease in heart rate and a decrease in the resistance of blood vessels, mean arterial pressure decreases. Arterial Baroreceptors (Slide 3) 1. There are two types of arterial baroreceptors. Type one are high pressure mechanoreceptors while type two are low pressure mechanoreceptors. 2. One set is located where the common carotid artery in the side of the neck branches into an internal and external branch. At this bifurcation, the internal branch swells, and this is called the carotid sinus. That is where the high pressure baroreceptors are located. A second set is located in the aortic arch. These are also high pressure receptors, called aortic baroreceptors. 3. The carotid sinus is structurally different from the carotid arteries themselves. The sinus has no smooth muscle in the wall but does have stiff little collagen protein and is made up primarily of elastin. It is very stretchable. The same is true of the aortic arch – the baroreceptors are located in a region that is physiologically different than the rest of the aortic arch. 4. There are other receptors in this area such as chemoreceptors that detect the chemistry of the blood. They are the carotid sinus chemoreceptors and aortic arch chemoreceptors. They are sensitive to chemicals such as changes in the partial pressure of oxygen, the partial pressure of carbon dioxide and in pH. Carotid Sinus Baroreceptors (Mechanoreceptor) And Afferent Pathways (Slide 4) 1. Baroreceptors are unmyelinated, bipolar neurons. The cell body is not located in the carotid sinus. It is in the ganglia closer to the brainstem. Tiny fibers spread out from the carotid sinus. They converge into a common nerve, called the Sinus, or Herring, nerve. The signals that are generated are sent to the 9th cranial nerve through a sensory afferent pathway. 2. There are aortic bipolar neurons in the aortic arch as well. 3. All afferent pathways lead directly into the central nervous system (CNS). Major Neural Pathways In The Control Of Cardiovascular Function (Slide 5) 1. There are regions in the medulla which contains neurons that regulate the cardiovascular system. 2. There is a nucleus called the NTS (nucleus tractus solitarius). This is the point where all signals from baroreceptors are conveyed to in the medulla. 3. Any neuron or group of neurons in the medulla that influence cardiovascular functions are collectively considered part of the medullary cardiovascular control center. They are not all located in one place. One part of the center mediates increases in heart rate (cardioacceleratory center), while another part slows down the heart rate (cardioinhibitory center). There is also a general vasomotor center. Actions within the vasomotor center can be vasodepressor (dilatory) or vasopressor (constrictatory) effects. Medullary Cardiovascular Control Centers, Their Afferent/Efferent Pathways, And Effectors (Slide 6) 1. Sensory input goes directly to the bilaterally located NTS. 2. There are other mechanical stretch receptors in the heart’s atrial tissue. These are low-pressure baroreceptors. They are connected by afferent sensory neurons that lead to the NTS as well. 3. The important point: sensory input is connected by interneurons to other regions of the control center, then to descending tracts that lead to the heart, vasculature and other tissues that participate in this regulation. Response Of Baroreceptors (Slide 7) 1. The sinus and aortic arch baroreceptors are the same in their function. 2. Under baseline conditions, there is a slight gradient in the frequency of action potentials. There is a greater frequency to the left than the right. This corresponds to rising pressure. During systole, as blood is filling, pressure is rising and baroreceptors are activated because the cardiac walls are being stretched. When pressure is decreasing during diastole, frequency decreases. The wall is being de- stretched. 3. When systemic arterial pressure (pressure within the carotid sinus) is increased, we seen an overall increase in action potential frequency compared to baseline conditions. However, the systole frequency is still higher than the diastole frequency. 4. When systemic arterial pressure (pressure within the carotid sinus) is decreased, we see an overall decrease in action potential frequency compared to baseline conditions. However, the systole frequency is still higher than the diastole frequency. 5. There are two stimuli that affect action potential frequency: mean arterial pressure (the magnitude of the pressure in the blood vessel) and pulsatile, or blood, pressure (the fact that pressure is changing throughout the cardiac cycle). Effects of Autonomic Nervous System On Pacemaker Potentials In SA Node (Slide 8) 1. The black lines are the basal resting rate. The green lines are a state of sympathetic nervous system activation. The blue line is a state of parasympathetic nervous system activation. 2. When the SNS is activated, heart rate increases. When the PSNS is activated, heart rate decreases. 3. This change in heart rate is detected by baroreceptors. If you compare the black line to the green line, when the SNS is activated, you increase the rate of depolarization of the SA node. Then, if you compare the black line to the blue line, when the PSNS is activated, you decrease the rate of depolarization of the SA node. 3. The Vagus nerve is so effective in the PSNS that if the pressure is high enough, it can stop your heart. This is called cardiac arrest and causes fainting. 4. Baroreceptors are very sensitive as well. If you wear a tie too tight, it can cause you to faint if the weather is too hot or humid. This is because baroreceptors can be stimulated by external influences. Vasovagal Syncope (Slide 9) 1. This is the effect of this regulatory system on your ability to remain conscious or unconscious. The idea is that emotional stress is important to mean arterial blood pressure. 2. It involves the cerebral cortex passing information from the hypothalamus to the medulla, causing some output either through sympathetic or parasympathetic (vagal). 3. Increasing vagal output decreases cardiac output as well as venous return. It will cause vasodilation or a decrease in peripheral resistance. This causes a sudden, marked decrease in arterial pressure. Cerebral blood flow decreases. Pressure will drop very low due to emotional states, temperature and a drop in central nervous system innervation. 4. At the same time, heart rate decreases as well, causing a severe drop in blood pressure. 5. With a reduction in blood flow, there is a reduction in atrial stretch. That signals the hypothalamus to release AVP (argenine vasopressin). This is the same as ADH. AVP will increase, and if you recover from syncope, and you are in an oliguric state. You do not have to go to the bathroom for several hours because water retention at the kidneys is maximized. Baroreceptor Reflex In Response To A Decrease In Systemic Arterial Pressure (Slide 10) 1. This slide was not covered in lecture, but it is a good summary of the baroreceptor reflex. 2. The initial cause of this reflex is a drop in mean arterial pressure. This leads arterial baroreceptors to decrease the frequency with which they conduct action potentials to the CNS. 3. This decreases is detected by the cardiovascular control center, which decreases parasympathetic and increase sympathetic nervous system actions. 4. This has four separate effects. a. SA Node – The SA node increases the frequency with which it releases action potentials, ultimately increasing heart rate. b. Ventricular Myocardium – The myocardium increases its contractility, increasing stroke volume. c. Veins – The veins in the body decrease their compliancy, increasing their pressure. This causes a higher stroke volume as well. d. Arterioles – The arterioles increase vasoconstriction, increasing total peripheral resistance and causing their pressure to increase. 5. All of this leads to a higher mean arterial pressure, which negatively feeds back to baroreceptors. Summary (Slide 11) 1. Remote control system was designed to maintain systemic arterial pressure near constant. 2. Sensors are located in key positions, and effectors are multiple. 3. Key components include medullary control centers, baroreceptors, nodal cells and vascular smooth muscle. 4. Because of these, systemic mean arterial pressure can be maintained near 100 mmHg over a lifetime (disease). Local Blood Flow Mechanisms (Slide 12) 1. Active (Exercise, functional) hyperemia 2. Reactive hyperemia 3. Pressure-flow autoregulation 4. Hyperemia = excess blood flow What Does Local Regulation Of Blood Flow Mean? (Slide 13) 1. Between an artery and a vein is a capillary bed to allow transfer. These local flow mechanisms help skeletal muscle take on more blood flow when its active than when its passive. 2. Local response means it occurs in the organ independent of the CNS. The controlling mechanisms usually lie in the arterioles. This does not mean there is no nervous integration to these organs. There is, but these local blood flow mechanisms take precedence. Local Regulation Of Blood Flow (Slide 14) 1. Displayed by many systemic organs and tissues. 2. Allows each organ to receive blood flow according to its metabolic needs for oxygen. 3. Pressure-flow autoregulation, reactive hyperemia, active (functional, exercise) hyperemia 4. Autoregulation perfected in renal circulation 5. Reactive hyperemia perfected in coronary circulation 5. Active hyperemia perfected in skeletal muscle circulation Active Hyperemia (Slide 15) 1. In a steady state condition, the tissue demands a certain amount of oxygen and releases a certain amount of byproducts. Oxygen supply and byproduct removal is adjusted accordingly. 2. In active muscles, the mechanism is local vasodilation. Arterioles relax, delivering more oxygen. Simultaneously, cells produce more carbon dioxide and release some potassium as well as other compounds that are dilators such as adenosine. These all act together to relax vascular smooth muscle. Increased blood flow causes more oxygen delivery and more carbon dioxide removal. 3. This occurs in skeletal muscles and the gut in the post-absorptive state. 4. So the ultimate cause of active hyperemia is an increase in metabolic rate, which is registered as an increase in O2 consumption and CO2 production. The tissue has a low concentration of O2 and a high concentration of CO2. This acts on the arteriolar smooth muscle to cause vasodilation and decrease resistance. These two factors increase blood flow, which increases O2 delivery and CO2 removal. The ultimate effect is an increase in tissue O2 concentration and a decrease in tissue CO2 concentration. 5. This has a negative feedback on the O2/CO2 concentration in the tissues. Active Hyperemia Versus The Myogenic Response (Slide 16) 1. The pressure gradient that drives blood flow through a given organ or tissue is called perfusion pressure. When this pressure increases, the arteriolar smooth muscle become stretched. To maintain homeostasis, vasoconstriction occurs, increasing resistance. The end result is a decrease in flow. This negatively feeds back to the perfusion pressure, which is balanced. 2. The difference between this myogenic response and active hyperemia is that hyperemia is caused by a change in O2/CO2 levels while myogenia is caused by a rise in perfusion pressure. Pressure-Flow Autoregulation (Slide 17) 1. Profusion pressure is the same as driving pressure. Starting at a profusion pressure of 100mmHg, you have a blood flow of about 2ml per minute per 100g of tissue. 2. If you increases profusion pressure, blood flow will rise instantaneously and passively. If pressure is maintained at that level for a while, flow will start coming back toward its baseline (pre-pressure elevated) level. 3. If you decrease profusion pressure, blood flow will drop instantaneously and passively. If pressure is maintained at that level for a while, flow will start coming back toward its baseline (pre-pressure depressed) level. 4. This is the definition of pressure-flow autoregulation. Blood flow does not change despite changes in pressure. There is also a negative-feedback mechanism. Increased profusion pressure causes arteriolar smooth muscle to increase. As this flow washes out and vascular smooth muscle cells respond myogenically (vascular cells sense stretch and can recoil), flow decreases again. Negative feedback takes the stimulus away. Reactive Hyperemia In Skeletal Muscle (Slide 18) 1. Under basal conditions, you have a flow rate of 50ml/minute and a profusion pressure of 120mmHg. 2. For a small amount of time, blood supply is stopped. Blood pressure drops and flow falls to 0. As long as blood flow is stopped, flow remains at 0. 3. As soon as blood flow is opened, pressure goes back to its baseline. However, flow goes up to its normal level, and then increases some more. This is reactive hyperemia. After a short period of time, flow returns to its baseline flow rate. 4. As the duration of blood flow cessation changes, so does the hyperemic response, proportionally. So the longer the occlusion (blood flow cessation), the greater the reactive hyperemic flow. 5. Mechanism: presence of vasodilators and vasoconstrictors that are washed out or allowed to accumulate AND myogenic response (greater response means greater vasculature will resist changes to flow and more autoregulation occurs). There is also a neurogenic component in all of these, but is not as well understood. The metabolic mechanism is more important than neurogenic in regulation of local blood flow in ALL organs 6. Side note: ischemia means reduced blood flow. Theories For How Local Flow Works (Slide 19) 1. Neurogenic, due to the innervation of the organ 2. Myogenic, due to VSM and endothelium 3. Metabolic, due to chemicals such as ADO Summary And Conclusions (Slide 20) 1. Local control means “at the tissue/organ level,” as opposed to centrally-mediated, i.e. remote 2. Blood flow in most organs is controlled locally even though it is subject to central influences. 3. In selected cases, e.g. a-v shunts in apical skin, the flow of blood is mainly controlled centrally. 4. There are three main local control modalities: active (functional, exercise) hyperemia, reactive hyperemia, pressure-flow autoregulation.