Vasodilation

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. 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. 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. 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. 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 (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. 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 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. 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. PDE5 inhibitors and potassium channel openers can also have similar results. Compounds that mediate the above mechanisms may be grouped as endogenous and exogenous. == Causes ==

Endogenous The vasodilating action of activation of beta-2 receptors (such as by adrenaline) appears to be endothelium-independent. Autonomic nervous system control As referenced in the explanation of smooth muscle physiology, smooth muscle within the tunica media is innervated by the autonomic nervous system. The autonomic nervous system (ANS) controls essential involuntary body functions and originates as nerves leaving the brain stem or spinal cord; it contains both sensor and motor nerves. Sympathetic nervous system activity, reduced blood volume or reduced arterial pressure trigger β-adrenergic receptors in select kidney cells Miscellaneous • Other suggested vasodilators or vasodilating factors include: • absence of high levels of environmental noise • adenosine - adenosine agonist, used primarily as an anti-arrhythmic • alpha blockers (block the vasoconstricting effect of adrenaline) • atrial natriuretic peptide (ANP) - a weak vasodilator • ethanol (alcohol) causes immediate vasodilation followed by increase in blood pressure • nitric oxide inducers • l-arginine (a key amino acid) • citrulline (causes increased levels of L-arginine in the body) • glyceryl trinitrate (commonly known as nitroglycerin) • isosorbide mononitrate and isosorbide dinitrate • pentaerythritol tetranitrate (PETN) • sodium nitroprusside • PDE5 inhibitors: these agents indirectly increase the effects of nitric oxide • sildenafil (Viagra) • tadalafil (Cialis) • vardenafil (Levitra) • tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis • theobromine, the principal alkaloid found in Theobroma cacao, specifically in cocoa solids (which is found in chocolate, especially dark chocolate) • minoxidil • papaverine an alkaloid found in the opium poppy papaver somniferum • estrogen == Treatment ==

Direct vasodilation drugs These drugs can keep vessels staying opened or help vessels refrain from being narrowed. • Angiotensin II receptor blockers • ACE inhibitors • Calcium channel blockers Alpha-2A adrenergic receptor agonists Drugs that appear to work by activating the α2A receptors in the brain thereby decreasing sympathetic nervous system activity. • methyldopa ::According to American Heart Association, Alpha-methyldopa may cause Orthostatic syncope as it exerts a greater blood pressure lowering effect when one is standing upright which may lead to feeling weak or fainting if the blood pressure has been lowered too far. Methyldopa's prominent side effects include drowsiness or sluggishness, dryness of the mouth, fever or anemia. Additionally to these, male patients may experience impotence. • clonidine hydrochloride • guanabenz acetate • guanfacine hydrochloride ::Clonidine, guanabenz or guanfacine may give rise to severe dryness of the mouth, constipation or drowsiness. Abrupt cessation taking may raise blood pressure quickly to dangerously high levels. Blood vessel muscle relaxants Directly relax the muscle in the walls of the blood vessels (especially the arterioles), allowing the vessel to dilate (widen). • hydralazine • minoxidil ::Hydralazine may cause headaches, swelling around the eyes, heart palpitations or aches and pains in the joints. In clinical setting, hydralazine is not usually used alone. ::Minoxidil is a potent direct vasodilator used only in resistant severe high blood pressure or when kidney failure is present. Noted adverse effects comprise fluid retention (marked weight gain) and excessive hair growth. == Therapeutic applications ==

Vasodilators are used to treat conditions such as hypertension, wherein the patient has an abnormally high blood pressure, as well as angina, congestive heart failure, and erectile dysfunction, and where maintaining a lower blood pressure reduces the patient's risk of developing other cardiac problems. Flushing may be a physiological response to vasodilators. Some phosphodiesterase inhibitors such as sildenafil, vardenafil and tadalafil, work to increase blood flow in the penis through vasodilation. They may also be used to treat pulmonary arterial hypertension (PAH). == See also ==