10.11: Neural Regulation of the Vascular System

The Cardiovascular Center 

Cardiovascular Center is situated in the medulla oblongata and regulates blood pressure and blood flow. It responds to various signals, including changes in blood pressure and the concentrations of oxygen, carbon dioxide, and hydrogen ions. The cardiovascular center is composed of three paired components:

1. Cardioaccelerator Centers: These centers stimulate cardiac function by regulating heart rate and stroke volume through sympathetic stimulation from the cardiac accelerator nerve. This results in an increase in heart rate and the force of heart contractions. When more blood is pumped with each beat, it can help raise blood pressure and increase blood flow to meet increased demand.

2. Cardioinhibitor Centers: In contrast, cardioinhibitor centers have the opposite effect. They slow down cardiac function by decreasing heart rate and stroke volume via parasympathetic stimulation from the vagus nerve. Reducing heart rate and the force of contractions is essential when the body needs to conserve energy or when lower blood pressure is required.

3. Vasomotor Centers: The vasomotor centers control the tone or contraction of the smooth muscle in the tunica media of blood vessels. Changes in the diameter of these blood vessels influence peripheral resistance, blood pressure, and blood flow, all of which impact cardiac output. The vasomotor centers primarily use the neurotransmitter norepinephrine to regulate vessel tone through sympathetic neurons and play a key role in regulating arteriolar constriction and dilation.

​Figure 14 | Summary of Factors Maintaining Vascular Homeostasis | ²²  This figure illustrates the complex interplay of local, neural, and endocrine mechanisms that regulate blood flow throughout the body. At the top, autoregulation is depicted, showing how tissues respond to changes in their local environment. Vasodilators, triggered by factors such as decreased oxygen or increased metabolites, relax precapillary sphincters, increasing blood flow and restoring homeostasis. Conversely, vasoconstrictors, like prostaglandins, constrict these sphincters, decreasing blood flow. The middle section outlines neural mechanisms, where blood pressure and chemistry are monitored by cardiac and vasomotor centers in the brain. Sympathetic stimulation increases cardiac output and blood flow, while parasympathetic stimulation decreases them. Additionally, vasoconstriction and vasodilation of peripheral vessels are mediated by neurotransmitters like norepinephrine and acetylcholine. The bottom section details endocrine control, featuring hormones such as erythropoietin, renin, catecholamines, antidiuretic hormone, and atrial natriuretic hormone, which regulate blood volume, pressure, and vessel tone, ultimately contributing to the maintenance of overall circulatory homeostasis. These mechanisms, which can be either short-term or long-term, ensure that blood flow is precisely matched to the metabolic needs of tissues and organs.

Acetylcholine released as part of parasympathetic activation, stimulates the endothelial cells lining the blood vessels to release nitric oxide, a potent vasodilator. Nitric oxide relaxes the smooth muscle in vessel walls, causing vasodilation. This vasodilation is crucial for increasing blood flow in response to local metabolic demands, like during exercise.

Arterioles are normally partially constricted due to sympathetic stimulation. Maximal sympathetic stimulation can lead to arteriolar constriction, reducing their radius to half their resting state. The suppression of sympathetic stimulation is necessary for full arteriolar dilation. When sympathetic activation is reduced, arterioles can expand by as much as 150 percent, significantly impacting peripheral resistance, blood pressure, and blood flow.

Baroreceptor Reflexes

Figure 15 | Baroreceptor Reflexes for Maintaining Vascular Homeostasis | ²³  This figure illustrates the baroreceptor reflex, a homeostatic mechanism that maintains blood pressure within a normal range. The top panel depicts the response to increased blood pressure. When blood pressure rises, baroreceptors in the aortic arch and carotid sinuses increase their firing rate. This increased signaling leads to decreased activity in the cardiac accelerator centers and the vasomotor center, while simultaneously increasing activity in the cardiac inhibitor centers. The result is a decrease in cardiac output (both heart rate and stroke volume) and vasodilation of blood vessels. These combined effects cause blood pressure to drop, restoring homeostasis. The bottom panel shows the response to decreased blood pressure. When blood pressure falls, baroreceptor firing decreases. This reduced signaling increases activity in the cardiac accelerator centers and the vasomotor center, while decreasing activity in the cardiac inhibitor centers. The consequent increase in cardiac output and vasoconstriction of blood vessels leads to a rise in blood pressure, again restoring homeostasis. 

Baroreceptors are specialized stretch receptors that monitor and respond to changes in blood pressure. Their role is critical in maintaining blood pressure within the normal range. Baroreceptors are primarily found in small cavities called sinuses within the aorta and carotid arteries, aortic sinuses (the walls of the ascending aorta, just superior to the aortic valve) and carotid sinuses (situated at the base of the internal carotid arteries.) Additional baroreceptors are low-pressure receptors located in the walls of the venae cavae (large veins) and the right atrium of the heart. When blood pressure increases, baroreceptors are stretched more tightly, resulting in an increased rate of action potentials. In contrast, when blood pressure drops, the degree of stretch in the baroreceptors decreases, leading to a slower firing rate. Baroreceptors send their signals to the cardiovascular center. This feedback loop helps maintain homeostasis of blood pressure. When blood pressure rises too high, the increased rate of baroreceptor firing initiates a reflex that triggers the parasympathetic stimulation of the heart, which, in turn, reduces cardiac output and causes vasodilation in the peripheral arterioles, ultimately lowering blood pressure. Conversely, when blood pressure drops too low, decreased baroreceptor firing stimulates the sympathetic nervous system to increase heart rate and cardiac output. It also induces vasoconstriction in peripheral blood vessels, raising blood pressure.

Baroreceptors in the venae cavae and right atrium monitor blood pressure as blood returns to the heart from systemic circulation. Normally, blood flow into the aorta matches the flow returning to the right atrium. If more blood is returning to the right atrium than is being ejected from the left ventricle (imbalanced flow), the atrial baroreceptors initiate a response. The atrial reflex then stimulates the cardiovascular centers to increase sympathetic firing, leading to an increase in cardiac output. This adjustment continues until homeostasis is achieved. The same mechanism operates in reverse if there is an imbalance in blood flow.

Chemoreceptor Reflexes

Chemoreceptors play a crucial role in maintaining vascular homeostasis by monitoring the blood levels of oxygen, carbon dioxide, and hydrogen ions. They are located in close proximity to baroreceptors in the aortic and carotid sinuses. Chemoreceptors signal the cardiovascular and respiratory centers in the medulla oblongata. During increased physical activity or when tissues require more oxygen, oxygen levels in the blood decrease, while carbon dioxide levels and hydrogen ion concentrations rise due to increased cellular respiration to meet energy demands. This leads to a reduction in blood pH (more acidic). In response to elevated carbon dioxide levels and increased hydrogen ion concentrations (falling pH), the chemoreceptors stimulate the cardioaccelerator and vasomotor centers in the cardiovascular center. This results in an increase in cardiac output (heart rate and stroke volume) and peripheral vasoconstriction. Conversely, during periods of rest or when the body's oxygen levels are sufficient, carbon dioxide levels decrease, hydrogen ion levels are reduced, and blood pH increases (becomes more alkaline). In response to decreasing carbon dioxide and hydrogen ion levels (increasing pH), the chemoreceptors stimulate the cardioinhibitor centers and suppress the cardioaccelerator and vasomotor centers in the cardiovascular center. This leads to a decrease in cardiac output and peripheral vasodilation.

Several other neural mechanisms can significantly impact cardiovascular function. The limbic system connects physiological responses to psychological stimuli, such as stress, fear, or emotional reactions. Generalized sympathetic and parasympathetic stimulation can also influence heart rate, peripheral resistance, and blood pressure.

Endocrine Regulation

Endocrine control of the cardiovascular system involves various hormones that help regulate blood pressure, blood volume, and overall cardiovascular function (Figure 16). They are listed below:

Epinephrine and Norepinephrine are released by the adrenal medulla in response to the "fight-or-flight" response. They increase heart rate and the force of cardiac contraction and temporarily constrict blood vessels to non-essential organs while directing blood flow to the brain, muscles, and the heart.

Antidiuretic hormone (ADH) is released by the hypothalamus primarily in response to increasing osmolarity of tissue fluid, often due to significant decrease in blood volume. ADH signals the kidneys to reabsorb more water, preventing additional fluid loss in urine. It constricts peripheral blood vessels, helping to increase blood pressure.

Renin-Angiotensin-Aldosterone Mechanism has a major effect on the cardiovascular system. Renin, released by specialized kidney cells in response to decreased blood flow, converts angiotensinogen (produced by the liver) into angiotensin I. Angiotensin I is converted into angiotensin II in the lungs by the enzyme angiotensin-converting enzyme. Angiotensin II is a powerful vasoconstrictor, significantly increasing blood pressure. It stimulates the release of ADH and aldosterone, a hormone produced by the adrenal cortex. Aldosterone increases sodium reabsorption by the kidneys, leading to water reabsorption and increasing blood volume and pressure. Angiotensin II also stimulates the thirst center in the hypothalamus, promoting increased fluid consumption.

Erythropoietin (EPO) is released by the kidneys when blood flow and/or oxygen levels decrease. It stimulates the production of red blood cells (erythrocytes) in the bone marrow. Erythrocytes contribute significantly to blood volume, viscosity, resistance, pressure, and flow. EPO also acts as a vasoconstrictor.

Atrial Natriuretic Hormone (ANH) is secreted by cells in the atria of the heart when blood volume causes extreme stretching of cardiac cells. It acts as an antagonist to angiotensin II. ANH promotes the loss of sodium and water from the kidneys. It suppresses the production and release of renin, aldosterone, and ADH. These actions collectively lead to a reduction in fluid retention, causing blood volume and pressure to decrease.²⁴

Figure 16 | Short-Term and Long-Term Responses to Decreased Blood Pressure and/or Volume | ²⁵ This figure illustrates the physiological mechanisms activated in response to a decrease in blood pressure or blood volume, categorized by their temporal scale. The "Short Term" response involves sympathetic activation, where the adrenal glands release epinephrine and norepinephrine. This leads to an increase in cardiac output and peripheral vasoconstriction, ultimately raising blood pressure. The "Long Term" responses primarily involve the kidneys. Renin is produced, which activates Angiotensin II, leading to the release of antidiuretic hormone and aldosterone, as well as stimulating thirst. These actions increase blood volume. Additionally, erythropoietin is produced, stimulating increased red blood cell formation, further contributing to the restoration of blood volume. 

Autoregulation of Perfusion

Autoregulation mechanisms require neither specialized nervous stimulation nor endocrine control. Rather, these are local self-regulatory mechanisms that allow each region of tissue to adjust its blood flow—and thus its perfusion. These local mechanisms include chemical signals and myogenic controls. The regulation of blood flow at the capillary level, primarily through the opening and closing of precapillary sphincters, is a critical mechanism to ensure that blood is directed to the tissues that need it most based on their metabolic requirements. Factors that trigger the opening or closing of these sphincters include low oxygen levels in the tissues that signal the need for increased blood flow to provide more oxygen. Elevated carbon dioxide levels indicate increased metabolic activity and the need for enhanced blood flow to remove carbon dioxide. The accumulation of waste products from cellular metabolism, like lactic acid, signals the need for more blood flow to remove these byproducts. Elevated potassium or hydrogen ion levels (lower pH) can indicate increased cellular activity and the need for more blood flow. Inflammatory responses trigger vasodilation to bring more blood and immune cells to the affected area. Elevated temperature is often associated with increased metabolic activity, and more blood flow is required to maintain tissue function. Nitric oxide is a potent vasodilator, relaxing the precapillary sphincters to allow more blood flow. On the other hand, high oxygen, low carbon dioxide, and low levels of metabolic byproducts signal reduced metabolic activity and the need for reduced blood flow. Release of endothelins, vasoconstricting peptides: Endothelins cause vasoconstriction, reducing blood flow. Platelet secretions and certain prostaglandins may also trigger vasoconstriction.

The myogenic response, on the other hand, is a mechanism that regulates blood flow in arterioles based on the stretching of the smooth muscle in their walls. It helps to maintain a stable blood flow in capillary networks. When blood flow is too low (ischemia) or too high, the smooth muscle in arterioles responds to maintain blood flow within the appropriate range. The smooth muscle relaxes in response to minimal stretching, leading to vasodilation and increased blood flow when needed. Conversely, when there is increased stretching, the smooth muscle contracts, causing vasoconstriction to reduce blood flow.¹⁷