Vasodilation
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel walls are composed of endothelial tissue and a basal membrane lining the lumen of the vessel, concentric smooth muscle layers on top of endothelial tissue, and an adventitia over the smooth muscle layers. Relaxation of the smooth muscle layer allows the blood vessel to dilate, as it is held in a semi-constricted state by sympathetic nervous system activity. Vasodilation is the opposite of vasoconstriction, which is the narrowing of blood vessels.
When blood vessels dilate, the flow of blood is increased due to a decrease in vascular resistance and increase in cardiac output. Vascular resistance is the amount of force circulating blood must overcome in order to allow perfusion of body tissues. Narrow vessels create more vascular resistance, while dilated vessels decrease vascular resistance. Vasodilation acts to increase cardiac output by decreasing afterload, −one of the four determinants of cardiac output.
By expanding available area for blood to circulate, vasodilation decreases blood pressure. The response may be intrinsic or extrinsic. In addition, the response may be localized to a specific organ, or it may be systemic.
Endogenous substances and drugs that cause vasodilation are termed vasodilators. Many of these substances are neurotransmitters released by perivascular nerves of the autonomic nervous system Baroreceptors sense blood pressure and allow adaptation via the mechanisms of vasoconstriction or vasodilation to maintain homeostasis.
Function
The primary function of vasodilation is to increase blood flow in the body to tissues that need it most. This is often in response to a localized need for oxygen but can occur when the tissue in question is not receiving enough glucose, lipids, or other nutrients. Vasodilation, both localized and systemic, also facilitates immune response. Localized tissues have multiple ways to increase blood flow, including releasing vasodilators, primarily adenosine, into the local interstitial fluid, which diffuses to capillary beds, provoking local vasodilation. Some physiologists have suggested that it is the lack of oxygen itself that causes capillary beds to vasodilate by the smooth muscle hypoxia of the vessels in the region. This latter hypothesis is posited due to the presence of precapillary sphincters in capillary beds. These approaches to the mechanism of vasodilation have not been found to be mutually exclusive.Immune system
Vasodilation plays a major role in immune system function. Wider blood vessels allow more blood containing immune cells and proteins to reach the infection site. Vasodilation occurs as part of the process of inflammation, which is caused by several factors including presence of a pathogen, injury to tissues or blood vessels, and immune complexes. In severe cases, inflammation can lead to sepsis or distributive shock. Vasodilation is also a major component of anaphylaxis.Inflammation causes not only vasodilation but also causes increased vascular permeability, allowing neutrophils, complement proteins, and antibodies to reach the site of infection or damage. Elevated vascular permeability can allow excess fluid to leave blood vessels and collect in tissues resulting in edema; vasodilation prevents blood vessels from constricting to adapt to reduced volume in the vessels, causing low blood pressure and septic shock.
In the case of inflammation, vasodilation is caused by cytokines. Interferon gamma, TNF-a, interleukin 1 beta, and interleukin 12 are a few examples of some inflammatory cytokines produced by immune cells such as natural killer cells, B cells, T cells, mast cells and macrophages. Anti-inflammatory cytokines that regulate inflammation and help prevent negative results such as septic shock are also produced by these immune cells. Vasodilation and increased vascular permeability also allow immune effector cells to leave blood vessels and follow chemoattractants to the infection site via a process called leukocyte extravasation. Vasodilation allows the same volume of blood to move more slowly according to the flow rate equation Q = Av, where Q represents flow rate, A represents cross-sectional area, and v represents velocity. Immune effector cells can more easily attach to selectins expressed on endothelial cells when blood is flowing slowly, enabling these cells to exit the blood vessel via diapedesis.
Anaphylaxis is a severe allergic reaction characterized by elevated vascular permeability, systemic vasodilation, gastrointestinal dysfunction, and respiratory dysfunction. Anaphylatoxins, specifically complement proteins C3a and C5a, bind to receptors on mast cells and basophils causing degranulation. Granules in these cells contain histamine, platelet-activating factor, and other compounds causing clinical manifestation of anaphylaxis- including systemic vasodilation causing dangerously low blood pressure. Immunoglobulin E, an antibody produced by plasma cells, also binds to receptors on mast cells and basophils causing degranulation.
Mechanism
A basic understanding of cardiac output, vascular resistance, and blood pressure is necessary to understand the causes and impacts of vasodilation. Cardiac output is defined as the amount of blood pumped through the heart over 1 minute, in units of liters per minute, equal to heart rate multiplied by stroke volume. It is directly related to heart rate, myocardial contractility, and preload, and inversely related with afterload. Elevated vascular resistance due to constricted blood vessels causes in increase in afterload, the amount of force against which the heart must contract. Vasodilation therefore decreases vascular resistance, which decreases afterload, elevating cardiac output and allowing perfusion of tissues. Blood pressure measures how much pressure blood exerts on blood vessel walls; systolic blood pressure measures pressure while the heart contracts, and diastolic blood pressure reflects pressure between contractions. Mean arterial pressure is a weighted average of systolic and diastolic blood pressures, and is a better measurement of perfusion over the duration of the cardiac cycle. Vasodilation works to decrease vascular resistance and blood pressure through relaxation of smooth muscle cells in the tunica media layer of large arteries and smaller arterioles. When vasodilation causes systolic blood pressure to fall below 90 mmHg, circulatory shock is observed.Vascular resistance depends on several factors, including the length of the vessel, the viscosity of blood and the diameter of the blood vessel. The latter is the most important variable in determining resistance, with the vascular resistance changing by the fourth power of the radius. An increase in either of these physiological components causes a rise in MAP. Arterioles create the most vascular resistance of any blood vessel type, as they are very narrow and possess concentric layers of smooth muscle unlike venules and capillaries.
Vasodilation occurs in superficial blood vessels of warm-blooded animals when their ambient environment is hot; this process diverts the flow of heated blood to the skin of the animal, where heat can be more easily released to the environment. The opposite physiological process is vasoconstriction. These processes are naturally modulated by local paracrine agents from endothelial cells, and by the autonomic nervous system and the adrenal glands, both of which secrete catecholamines, such as norepinephrine and epinephrine, respectively.
Smooth muscle physiology
The tunica media of the walls of arteries, arterioles, and veins is composed of smooth muscle and causes vasodilation and vasoconstriction. Contraction of smooth muscle cells causes vasoconstriction, and relaxation of smooth muscle causes vasodilation. Smooth muscle is innervated by the autonomic nervous system and is non-striated. Contraction is dependent on concentrations of Ca2+ in the cytosol, either via Ca,Mg-ATPase from the sarcoplasmic reticulum or voltage-gated calcium channels from the extracellular matrix. Calcium ions bind with calmodulin, activating myosin light-chain kinase which phosphorylates the myosin light-chain. Phosphorylated light-chain myosin interacts with actin filaments forming a cross-bridge, allowing muscle contraction causing vasoconstriction. Vasodilation is caused by myosin-light-chain phosphatase, which dephosphorylates the myosin light chain causing muscle relaxation. Smooth muscle cells can remain contracted without use of ATP due to action of the myosin-binding subunit of myosin light-chain phosphatase. Phosphorylation of this subunit by Rho-kinase prevents it from binding to and dephosphorylating the myosin light-chain, allowing the cell to remain contracted.Vasodilation is the result of relaxation in smooth muscle surrounding the blood vessels. This relaxation, in turn, relies on removing the stimulus for contraction, which depends on intracellular calcium ion concentrations and is tightly linked with phosphorylation of the light chain of the contractile protein myosin. Thus, vasodilation works mainly either by lowering intracellular calcium concentration or by dephosphorylation of myosin. Dephosphorylation by myosin light-chain phosphatase and induction of calcium symporters and antiporters that pump calcium ions out of the intracellular compartment both contribute to smooth muscle cell relaxation and therefore vasodilation. This is accomplished through reuptake of ions into the sarcoplasmic reticulum via exchangers and expulsion across the plasma membrane. There are three main intracellular stimuli that can result in the vasodilation of blood vessels. The specific mechanisms to accomplish these effects vary from vasodilator to vasodilator.
| Class | Description | Example |
| Hyperpolarization-mediated | Changes in the resting membrane potential of the cell affects the level of intracellular calcium through modulation of voltage-sensitive calcium channels in the plasma membrane. | adenosine |
| cAMP-mediated | Adrenergic stimulation results in elevated levels of cAMP and protein kinase A, which results in increasing calcium removal from the cytoplasm. | prostacyclin |
| cGMP-mediated | Through stimulation of protein kinase G. | nitric oxide |
PDE5 inhibitors and potassium channel openers can also have similar results.
Compounds that mediate the above mechanisms may be grouped as endogenous and exogenous.