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Vasodilation, also known as vasorelaxation, is the widening of . It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large , large Artery, and smaller . 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 , the Blood flow 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 (due to local processes in the surrounding tissue) or extrinsic (due to or the nervous system). In addition, the response may be localized to a specific organ (depending on the Metabolism needs of a particular tissue, as during strenuous exercise), or it may be systemic (seen throughout the entire systemic circulation).
Endogenous substances and that cause vasodilation are termed vasodilators. Many of these substances are released by perivascular nerves of the autonomic nervous system sense blood pressure and allow adaptation via the mechanisms of vasoconstriction or vasodilation to maintain homeostasis.
Inflammation causes not only vasodilation but also causes increased vascular permeability, allowing , 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 . 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, , , and . 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 to leave blood vessels and follow 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 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. , 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 , also binds to receptors on mast cells and basophils causing degranulation.
Vascular resistance depends on several factors, including the length of the vessel, the viscosity of blood (determined by hematocrit) 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 (cardiac output or vascular resistance) causes a rise in MAP. create the most vascular resistance of any blood vessel type, as they are very narrow and possess concentric layers of smooth muscle unlike and Capillary.
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 (e.g., nitric oxide, bradykinin, Potassium, and adenosine), and by the autonomic nervous system and the , both of which secrete catecholamines, such as norepinephrine and epinephrine, respectively.
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 (really substitution of ATP for ADP) 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.
| Hyperpolarization-mediated (Calcium channel blocker) | 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 (Nitrovasodilator) | 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.
| ? | hyperpolarization → ↓VDCC → ↓intracellular Ca2+ |
PKG activity →
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| ↓endothelin synthesis | |
| β-2 adrenergic receptor | ↑Gs activity → ↑AC activity → ↑cyclic AMP → ↑PKA activity → phosphorylation of MLCK → ↓MLCK activity → dephosphorylation of MLC |
| histamine H2 receptor | |
| IP receptor | |
| DP receptor | |
| EP receptor | |
↑Gs activity → ↑AC activity → ↑cyclic AMP → ↑PKA activity →
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| ↑ATP-sensitive K+ channel → hyperpolarization → close VDCC → ↓intracellular Ca2+ | |
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| Gi → ↓cyclic AMP → activation of Na+/K+-ATPase → ↓intracellular sodium → ↑Na+/Ca2+ exchanger activity → ↓intracellular Ca2+ | |
| - | ↓interstitial pH → ? |
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Neurotransmitters can act by binding directly to smooth muscle cells or by binding to endothelial cells mediating the effects of the neurotransmitter. Below is a table summarizing major neurotransmitters involved in regulation of the vasculature.
| + !Neurotransmitter !Sympathetic or Parasympathetic !Target Cells and Receptors !Impact on Vasculature | |||
| norepinephrine (NE) | sympathetic (mostly) | adrenergic receptors α1, α2, β1, β2 α1- smooth muscle α2- endothelial β1, β2- smooth muscle | α1- increase concentration calcium ions, vasoconstricton α2- inhibit cAMP, release NO, vasodilation β1, β2- possible vasodilation |
| Acetylcholine (Ach) | parasympathetic | nicotonic Ach receptors (nAchRs) muscanaric Ach receptors (mAchRs) - on both endothelial and smooth muscle cells | nAchRs- modulate cytokines, counteract inflammation mAchRs- endothelial M3 AchR release NO, vasodlation smooth muscle M2 and M3 AchRs reduce release NO, vasoconstriction Note: Ach is quickly broken down, diffused, or undergoes reuptake, impacts are brief and localized |
| Adenosine triphosphate (ATP) | sympathetic | purinergic receptors on smooth muscle and endothelial cells | smooth muscle- increase calcium ion concentration, vasoconstriction endothelium- possible role as mediator of hyperpolarization of smooth muscle cells co-released with norepinephrine |
| Neuropeptide Y (NPY) | sympathetic | receptors on endothelial cells | causes vasoconstriction when co-released with norepinephrine |
| CGRP | ? | CGRP1, CGRP2 receptors in endothelium | vasodilation, role in vascular dysfunction if levels are abnormal |
Epinephrine, either exogenous or endogenous, is another vasoconstrictor released by the adrenal glands in response to stress. It binds to α and β adrenergic receptors like norepinephrine, causing vasodilation and vasoconstriction in different body parts to redistribute circulation to critical areas.
When the fingers are exposed to cold, vasoconstriction occurs first to reduce heat loss, resulting in strong cooling of the fingers. Approximately five to ten minutes after the start of the cold exposure of the hand, the blood vessels in the finger tips will suddenly vasodilate. This is probably caused by a sudden decrease in the release of from the sympathetic nerves to the muscular coat of the arteriovenous anastomoses due to local cold. The CIVD increases blood flow and subsequently the temperature of the fingers. This can be painful and is sometimes known as the 'hot aches' which can be painful enough to bring on vomiting.
A new phase of vasoconstriction follows the vasodilation, after which the process repeats itself. This is called the Hunting reaction. Experiments have shown that three other vascular responses to immersion of the finger in cold water are possible: a continuous state of vasoconstriction; slow, steady, and continuous rewarming; and a proportional control form in which the blood vessel diameter remains constant after an initial phase of vasoconstriction. However, the vast majority of responses can be classified as the Hunting reaction.
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