Vasodilation
Encyclopedia
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...

 cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...

, or the narrowing of blood vessels. When vessels dilate, the flow of blood is increased due to a decrease in vascular resistance
Vascular resistance
Vascular resistance is a term used to define the resistance to flow that must be overcome to push blood through the circulatory system. The resistance offered by the peripheral circulation is known as the systemic vascular resistance , while the resistance offered by the vasculature of the lungs...

. Therefore, dilation of arterial blood vessels (mainly arterioles) leads to a decrease in blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

. The response may be intrinsic (due to local processes in the surrounding tissue) or extrinsic (due to hormones or the nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...

). Additionally, the response may either be localized to a specific organ (depending on the metabolic needs of a particular tissue, as during strenuous exercise), or systemic (seen throughout the entire systemic circulation
Systemic circulation
Systemic circulation is the part of the cardiovascular system which carries oxygenated blood away from the heart to the body, and returns deoxygenated blood back to the heart. This physiologic theory of circulation was first described by William Harvey...

). Factors that result in vasodilation are termed vasodilators.

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 of oxygen, but can occur when the tissue in question is not receiving enough glucose or lipids or other nutrients. Localized tissues utilize multiple ways to increase blood flow including releasing vasodilators, primarily adenosine, into the local instersitial fluid which diffuses to capillary beds provoking local vasodilation. Some physiologists have suggested it is the lack of oxygen itself which 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 sphincter
Precapillary sphincter
The precapillary sphincter is a band of smooth muscle that adjusts the blood flow into each capillary. At the point where each true capillary originates from a metarteriole, a smooth muscle fiber usually encircles the capillary. This is called the precapillary sphincter. This sphincter can open and...

s in capillary beds. Neither of these approaches to the mechanism of vasodilation is mutually exclusive of the other.

Vasodilation and arterial resistance

Vasodilation directly affects the relationship between mean arterial pressure
Mean arterial pressure
The mean arterial pressure is a term used in medicine to describe an average blood pressure in an individual. It is defined as the average arterial pressure during a single cardiac cycle.-Calculation:...

, cardiac output
Cardiac output
Cardiac output is the volume of blood being pumped by the heart, in particular by a left or right ventricle in the time interval of one minute. CO may be measured in many ways, for example dm3/min...

 and total peripheral resistance
Total peripheral resistance
Vasculature throughout the entire body can be thought of as two separate circuits - one is the systemic circulation, while the other is the pulmonary circulation. Total peripheral resistance is the sum of the resistance of all peripheral vasculature in the systemic circulation...

 (TPR). Vasodilation occurs in the time phase of cardiac systole while vasoconstriction follows in the opposite time phase of cardiac diastole. Mathematically, cardiac output (blood flow measured in volume per unit time) is computed by multiplying the heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....

 (in beats per minute) and the stroke volume
Stroke volume
In cardiovascular physiology, stroke volume is the volume of blood pumped from one ventricle of the heart with each beat. SV is calculated using measurements of ventricle volumes from an echocardiogram and subtracting the volume of the blood in the ventricle at the end of a beat from the volume...

 (the volume of blood ejected during ventricular systole
Systole (medicine)
Systole is the contraction of the heart. Used alone, it usually means the contraction of the left ventricle.In all mammals, the heart has 4 chambers. The left and right ventricles pump together. The atria and ventricles pump in sequence...

). TPR depends on several factors, including the length of the vessel, the viscosity of blood (determined by hematocrit
Hematocrit
The hematocrit or packed cell volume or erythrocyte volume fraction is the percentage of the concentration of red blood cells in blood. It is normally about 45% for men and 40% for women...

) and the diameter of the blood vessel. The latter is the most important variable in determining resistance, with the TPR changing by the fourth power of the radius. An increase in either of these physiological components (cardiac output or TPR) cause a rise in the mean arterial pressure. Vasodilation works to decrease TPR and blood pressure through relaxation of smooth muscle cells in the tunica media
Tunica media
The tunica media is the middle layer of an artery or vein.-Artery:It is made up of smooth muscle cells and elastic tissue...

 layer of large arteries and smaller arterioles.

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 into the atmosphere. The opposite physiological process is vasoconstriction
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...

. These processes are naturally modulated by local paracrine agents from endothelial cells (e.g. nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...

, bradykinin
Bradykinin
Bradykinin is a peptide that causes blood vessels to dilate , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...

, potassium ions and adenosine), as well as an organism's autonomic nervous system
Autonomic nervous system
The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...

 and adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

s, both of which secrete catecholamines such as norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

 and epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

, respectively.

Examples and individual mechanisms

Vasodilation is the result of relaxation in smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...

 surrounding the blood vessels. This relaxation, in turn, relies on removing the stimulus for contraction, which depends on intracellular calcium ion concentrations and, consequently, phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

 of the light chain of the contractile protein myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...

. Thus, vasodilation mainly works either by lowering intracellular calcium concentration or the dephosphorylation of myosin. This includes stimulation of myosin light chain phosphatase and induction of calcium symporters and antiporters that pump calcium ions out of the intracellular compartment. 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
Hyperpolarization
Hyperpolarization has several meanings:* Hyperpolarization occurs when the strength of the electric field across the width of a cell membrane increases...

 mediated (Calcium channel blocker
Calcium channel blocker
A calcium channel blocker is a chemical that disrupts the movement of calcium through calcium channels.CCB drugs devised to target neurons are used as antiepileptics. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with...

)
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
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...

 mediated
Adrenergic
Adrenergic
An adrenergic agent is a drug, or other substance, which has effects similar to, or the same as, epinephrine . Thus, it is a kind of sympathomimetic agent...

 stimulation results in elevated levels of cAMP and protein kinase A, which results in increasing calcium removal from the cytoplasm.
prostacyclin
Prostacyclin
Prostacyclin is a member of the family of lipid molecules known as eicosanoids.As a drug, it is also known as "epoprostenol". The terms are sometimes used interchangeably.-History:...

cGMP
Cyclic guanosine monophosphate
Cyclic guanosine monophosphate is a cyclic nucleotide derived from guanosine triphosphate . cGMP acts as a second messenger much like cyclic AMP...

 mediated (Nitrovasodilator
Nitrovasodilator
A nitrovasodilator is an agent which causes vasodilation by donation of nitric oxide.Examples include nitroprusside and nitroglycerine.-References:...

)
Through stimulation of protein kinase G. nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...



PDE5 inhibitor
PDE5 inhibitor
A phosphodiesterase type 5 inhibitor, often shortened to PDE5 inhibitor, is a drug used to block the degradative action of phosphodiesterase type 5 on cyclic GMP in the smooth muscle cells lining the blood vessels supplying the corpus cavernosum of the penis...

s and potassium channel opener
Potassium channel opener
A potassium channel opener is a type of drug which facilitates ion transmission through potassium channels.Some examples include:* Diazoxide vasodilator used for hypertension, smooth muscle relaxing activity...

s can also have similar results.

Compounds that mediate the above mechanisms may be grouped as endogenous
Endogenous
Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...

 and exogenous
Exogenous
Exogenous refers to an action or object coming from outside a system. It is the opposite of endogenous, something generated from within the system....

.

Endogenous

Vasodilators Receptor
(↑ = opens. ↓ = closes)
On vascular smooth muscle cells if not otherwise specified
Transduction
(↑ = increases. ↓ = decreases)
EDHF  ? hyperpolarization
Hyperpolarization
Hyperpolarization has several meanings:* Hyperpolarization occurs when the strength of the electric field across the width of a cell membrane increases...

 --> ↓VDCC
Voltage-dependent calcium channel
Voltage-dependent calcium channels are a group of voltage-gated ion channels found in excitable cells with a permeability to the ion Ca2+...

 --> ↓intracellular Ca2+
depolarization
Depolarization
In biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative. In neurons and some other cells, a large enough depolarization may result in an action potential...

 
↑voltage-gated K+ channel
interstitial
Interstitial fluid
Interstitial fluid is a solution that bathes and surrounds the cells of multicellular animals. It is the main component of the extracellular fluid, which also includes plasma and transcellular fluid...

 K+
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...

 
directly
nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...

 
↑NO receptor on smooth muscle ↑cGMP --> ↑PKG activity -->
  • phosphorylation of MLCK --> ↓MLCK activity --> dephosphorylation of MLC
  • SERCA
    SERCA
    SERCA, or sarco/endoplasmic reticulum Ca2+-ATPase, or SR Ca2+-ATPase, is a calcium ATPase-type P-ATPase.-Function:SERCA resides in the sarcoplasmic reticulum within muscle cells...

     --> ↓intracellular Ca2+
NO receptor on endothelium
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...

 
endothelin
Endothelin
Endothelins are proteins that constrict blood vessels and raise blood pressure. They are normally kept in balance by other mechanisms, but when they are over-expressed, they contribute to high blood pressure and heart disease....

 synthesis
noradrenaline  β-2 adrenergic receptor
Beta-2 adrenergic receptor
The beta-2 adrenergic receptor , also known as ADRB2, is a beta-adrenergic receptor, and also denotes the human gene encoding it.-Gene:The gene is intronless...

Gs
Gs alpha subunit
The Gs alpha subunit is a heterotrimeric G protein subunit that activates the cAMP-dependent pathway by activating adenylate cyclase.-Receptors:The G protein-coupled receptors that couple to this kind of G-protein include:...

 activity --> ↑AC
Adenylate cyclase
Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell ....

 activity --> ↑cAMP --> ↑PKA activity --> phosphorylation of MLCK --> ↓MLCK activity --> dephosphorylation of MLC
histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...

 
histamine H1 receptor
prostacyclin
Prostacyclin
Prostacyclin is a member of the family of lipid molecules known as eicosanoids.As a drug, it is also known as "epoprostenol". The terms are sometimes used interchangeably.-History:...

 
IP receptor
prostaglandin D2
Prostaglandin D2
Prostaglandin D2 is a prostaglandin that binds to the receptor PTGDR, as well as CRTH2. It is a major prostaglandin produced by mast cells – recruits Th2 cells, eosinophils, basophils. In mammalian organs, large amounts of PGD2 are found in the brain, in mast cells and found nowhere else...

 
DP receptor
prostaglandin E2  EP receptor
VIP
Vasoactive intestinal peptide
Vasoactive intestinal peptide also known as the vasoactive intestinal polypeptide or VIP is a peptide hormone containing 29 amino acid residues that is produced in many tissues of vertebrates including the gut, pancreas and suprachiasmatic nuclei of the hypothalamus in the brain...

 
VIP receptor
Vasoactive intestinal peptide receptor
There are two known receptors for the vasoactive intestinal peptide termed VPAC1 and VPAC2. These receptors bind both VIP and pituitary adenylate cyclase-activating polypeptide to some degree...

 
Gs
Gs alpha subunit
The Gs alpha subunit is a heterotrimeric G protein subunit that activates the cAMP-dependent pathway by activating adenylate cyclase.-Receptors:The G protein-coupled receptors that couple to this kind of G-protein include:...

 activity --> ↑AC
Adenylate cyclase
Adenylate cyclase is part of the G protein signalling cascade, which transmits chemical signals from outside the cell across the membrane to the inside of the cell ....

 activity --> ↑cAMP --> ↑PKA activity -->
  • phosphorylation of MLCK --> ↓MLCK activity --> dephosphorylation of MLC
  • open Ca2+-activated
    Calcium-activated potassium channel
    Calcium-activated potassium channels are divided into BK channels, IK channels, and SK channels based on their conductance ....

     and voltage-gated K+channel
    Voltage-gated potassium channel
    Voltage-gated potassium channels are transmembrane channels specific for potassium and sensitive to voltage changes in the cell's membrane potential. During action potentials, they play a crucial role in returning the depolarized cell to a resting state....

    s --> hyperpolarization --> close VDCC
    Voltage-dependent calcium channel
    Voltage-dependent calcium channels are a group of voltage-gated ion channels found in excitable cells with a permeability to the ion Ca2+...

     --> ↓intracellular Ca2+
  • (extracellular) adenosine  A1, A2a
    Adenosine A2A receptor
    The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, but also denotes the human gene encoding it.-Structure:This protein is a member of the G protein-coupled receptor family which possess seven transmembrane alpha helices...

     and A2b
    Adenosine A2b receptor
    The adenosine A2B receptor, also known as ADORA2B, is a G-protein coupled adenosine receptor, and also denotes the human adenosine A2b receptor gene which encodes it....

     adenosine receptors 
    ↑ATP-sensitive K+ channel --> hyperpolarization --> close VDCC
    Voltage-dependent calcium channel
    Voltage-dependent calcium channels are a group of voltage-gated ion channels found in excitable cells with a permeability to the ion Ca2+...

     --> ↓intracellular Ca2+
  • (extracellular) ATP
    Adenosine triphosphate
    Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

  • (extracellular) ADP
    Adenosine diphosphate
    Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

  • P2Y receptor
    P2Y receptor
    P2Y receptors are a family of purinergic receptors, G protein-coupled receptors stimulated by nucleotides such as ATP, ADP, UTP, UDP and UDP-glucose...

     
    activate Gq
    Gq alpha subunit
    Gq protein or Gq/11 is a heterotrimeric G protein subunit that activates phospholipase C . PLC in turn hydrolyzes Phosphatidylinositol 4,5-bisphosphate to diacyl glycerol and inositol triphosphate signal transduction pathway...

     --> ↑PLC
    Phospholipase C
    Phosphoinositide phospholipase C is a family of eukaryotic intracellular enzymes that play an important role in signal transduction processes. In general, this enzyme is denoted as Phospholipase C, although three other families of phospholipase C enzymes have been identified in bacteria and in...

     activity --> ↑intracellular Ca2+ --> ↑NOS
    Nitric oxide synthase
    Nitric oxide synthases are a family of enzymes that catalyze the production of nitric oxide from L-arginine. NO is an important cellular signaling molecule, having a vital role in many biological processes...

     activity --> ↑NO
    Nitric oxide
    Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...

     --> (see nitric oxide)
    L-arginine
    Arginine
    Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...

     
    imidazoline
    Imidazoline receptor
    Imidazoline receptors are receptors for clonidine and other imidazolines.-Classes:There are three classes of imidazoline receptors:* I1 receptor – mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure, * I2 receptor – an allosteric binding site of monoamine oxidase and is...

     and α-2 receptor
    Alpha-2 adrenergic receptor
    The alpha-2 adrenergic receptor is a G protein-coupled receptor associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well...

    ?
    Gi
    Gi alpha subunit
    Gi alpha subunit is a heterotrimeric G protein subunit that inhibits the production of cAMP from ATP.- Receptors :The following G protein-coupled receptors couple to the Gi subunit:* Acetylcholine M2 & M4 receptors...

     --> ↓cAMP --> activation of Na+/K+-ATPase
    Na+/K+-ATPase
    Na+/K+-ATPase is an enzyme located in the plasma membrane in all animals.- Sodium-potassium pumps :Active transport is responsible for cells containing relatively high...

     --> ↓intracellular Na+
    Sodium
    Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

     --> ↑Na+/Ca2+ exchanger
    Sodium-calcium exchanger
    The sodium-calcium exchanger is an antiporter membrane protein that removes calcium from cells. It uses the energy that is stored in the electrochemical gradient of sodium by allowing Na+ to flow down its gradient across the plasma membrane in exchange for the countertransport of calcium ions...

     activity --> ↓intracellular Ca2+
    bradykinin
    Bradykinin
    Bradykinin is a peptide that causes blood vessels to dilate , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...

     
    bradykinin receptor
    Bradykinin receptor
    The bradykinin receptor family is a group of G-protein coupled receptors whose principal ligand is the protein bradykinin.There are two Bradykinin receptors: the B1 receptor and the B2 receptor.-B1 receptor:...

    substance P
    Substance P
    In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...

     
    niacin
    Niacin
    "Niacin" redirects here. For the neo-fusion band, see Niacin .Niacin is an organic compound with the formula and, depending on the definition used, one of the forty to eighty essential human nutrients.Niacin is one of five vitamins associated with a pandemic deficiency disease: niacin deficiency...

     (as nicotinic acid only)
    platelet activating factor (PAF)
    CO2
    Carbon dioxide
    Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...

     
    - interstitial
    Interstitial fluid
    Interstitial fluid is a solution that bathes and surrounds the cells of multicellular animals. It is the main component of the extracellular fluid, which also includes plasma and transcellular fluid...

     pH
    PH
    In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...

     --> ?
    interstitial
    Interstitial fluid
    Interstitial fluid is a solution that bathes and surrounds the cells of multicellular animals. It is the main component of the extracellular fluid, which also includes plasma and transcellular fluid...

     lactic acid
    Lactic acid
    Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...

    (probably)
    -
    muscle work -
  • ↑vasodilators:
    • ATP
      Adenosine triphosphate
      Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

       consumption --> ↑adenosine
    • glucose
      Glucose
      Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

       usage --> CO2
      Carbon dioxide
      Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...

    • interstitial
      Interstitial fluid
      Interstitial fluid is a solution that bathes and surrounds the cells of multicellular animals. It is the main component of the extracellular fluid, which also includes plasma and transcellular fluid...

       K+
      Sodium
      Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

    • ↑(extracellular) ATP
      Adenosine triphosphate
      Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

    • ↑(extracellular) ADP
      Adenosine diphosphate
      Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

    • interstitial
      Interstitial fluid
      Interstitial fluid is a solution that bathes and surrounds the cells of multicellular animals. It is the main component of the extracellular fluid, which also includes plasma and transcellular fluid...

       K+
      Potassium
      Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...


    • ↓vasoconstrictors:
      • ATP
        Adenosine triphosphate
        Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

         consumption --> ↓ ATP (intracellular)
      • oxygen
        Oxygen
        Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

         --> ↓oxidative phosphorylation
        Oxidative phosphorylation
        Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate . Although the many forms of life on earth use a range of different nutrients, almost all aerobic organisms carry out oxidative phosphorylation to produce ATP,...

         --> ↓ ATP (intracellular)
  • natriuretic peptide
    Natriuretic peptide
    Natriuretic peptide refers to a peptide which induces natriuresis .Types include:* Atrial natriuretic peptide: atria* Brain natriuretic peptide: ventricles in humans, brains in pigs* C-type natriuretic peptide...

    s
  • prostaglandin I2
  • prostaglandin E2
  • heparin
    Heparin
    Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...

  • high shear stress
    Shear stress
    A shear stress, denoted \tau\, , is defined as the component of stress coplanar with a material cross section. Shear stress arises from the force vector component parallel to the cross section...

  • various receptors on endothelium
    Endothelium
    The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...

     
    endothelin
    Endothelin
    Endothelins are proteins that constrict blood vessels and raise blood pressure. They are normally kept in balance by other mechanisms, but when they are over-expressed, they contribute to high blood pressure and heart disease....

     synthesis

    The vasodilating action of activation of beta-2 receptors (such as by noradrenaline) appears to be endothelium
    Endothelium
    The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...

    -independent.

    Sympathetic nervous system vasodilation

    Whereas it is recognized that that the sympathetic nervous system plays an expendable role in vasodilation, it is one of the mechanisms by which it can be accomplished. The spinal cord has both vasodilation and vasoconstriction
    Vasoconstriction
    Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...

     nerves. The neurons that control vascular vasodilation originate in the hypothalmus. Some sympathetic stimulation of arterioles in skeletal muscle is mediated by epinephrine acting on β-adrenergic receptors of arteriolar smooth muscle which would be mediated by cAMP pathways as mentioned above. However, it has been shown that knocking out this sympathetic stimulation plays little to no role in whether skeletal muscle is able to receive sufficient oxygen even at high levels of exertion, so it is believed that this particular method of vasodilation is of little import to human physiology.

    In cases of emotional distress, this system may activate, resulting in fainting due to decreased blood pressure from vasodilation, which is referred to as vasovagal syncope
    Vasovagal syncope
    A vasovagal episode or vasovagal response or vasovagal attack is a malaise mediated by the vagus nerve. When it leads to syncope or "fainting", it is called a vasovagal syncope, which is the most common type of fainting.There are a number of different syncope syndromes which all fall under the...

    .

    Other mechanisms of vasodilation

    Other suggested vasodilators or vasodilating factors include:
    • absence of high levels of environmental noise
      Environmental noise
      Environmental noise is the summary of noise from transport, industrial and recreational activities.The definition is pursuant to the directive 2002/49/EC article 10.1. This directive should give a common approach intended to avoid, prevent or reduce the harmful effects of environmental noise. The...

    • absence of high levels of illumination
      Over-illumination
      Over-illumination is the presence of lighting intensity beyond that required for a specified activity. Over-illumination was commonly ignored between 1950 and 1995, especially in office and retail environments; only since then has the interior design community begun to reconsider this practice.The...

    • Adenocard - adenosine agonist, primarily used as an antiarrhythmic
    • alpha blocker
      Alpha blocker
      Alpha-1 blockers constitute a variety of drugs which block α1-adrenergic receptors in arteries and smooth muscles.-Pharmacology:...

      s (block the vasoconstricting effect of adrenaline)
    • amyl nitrite
      Amyl nitrite
      Amyl nitrite is the chemical compound with the formula C5H11ONO. A variety of isomers are known, but they all feature an amyl group attached to the nitrito functional group. The alkyl group is unreactive and the chemical and biological properties are mainly due to the nitrite group...

       and other nitrites are often used recreationally as a vasodilator, causing lightheadedness and a euphoric feeling
    • atrial natriuretic peptide
      Atrial natriuretic peptide
      Atrial natriuretic peptide , atrial natriuretic factor , atrial natriuretic hormone , or atriopeptin, is a powerful vasodilator, and a protein hormone secreted by heart muscle cells. It is involved in the homeostatic control of body water, sodium, potassium and fat...

       (ANP) - a weak vasodilator
    • capsaicin
      Capsaicin
      Capsaicin 2CHCH=CH4CONHCH2C6H3-4--3- ) is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact...

       (chili) [not necessarily safe for diabetics]
    • ethanol
      Ethanol
      Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

       (alcohol)
    • histamine-inducers
      • Complement
        Complement system
        The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...

         proteins C3a, C4a and C5a work by triggering histamine release from mast cell
        Mast cell
        A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...

        s and basophil granulocyte
        Basophil granulocyte
        Basophil granulocytes, sometimes referred to as basophils, are the least common of the granulocytes, representing about 0.01% to 0.3% of circulating white blood cells....

        s.
    • nitric oxide inducers
      • glyceryl trinitrate (commonly known as nitroglycerin)
      • isosorbide mononitrate and isosorbide dinitrate
        Isosorbide dinitrate
        Isosorbide dinitrate is a nitrate used pharmacologically as a vasodilator, e.g. in angina pectoris but also for anal fissure, a condition which is known to involve decreased blood supply leading to poor healing...

      • pentaerythritol tetranitrate
        PETN
        Pentaerythritol tetranitrate , also known as PENT, PENTA, TEN, corpent, penthrite , is the nitrate ester of pentaerythritol. Penta refers to the five carbon atoms of the neopentane skeleton.PETN is most well known as an explosive...

         (PETN)
      • sodium nitroprusside
        Sodium nitroprusside
        Sodium nitroprusside is the inorganic compound with the formula Na2[Fe5NO]·2H2O. This red-coloured salt, which is often abbreviated SNP, is a potent vasodilator...

      • PDE5 inhibitor
        PDE5 inhibitor
        A phosphodiesterase type 5 inhibitor, often shortened to PDE5 inhibitor, is a drug used to block the degradative action of phosphodiesterase type 5 on cyclic GMP in the smooth muscle cells lining the blood vessels supplying the corpus cavernosum of the penis...

        s: these agents indirectly increase the effects of nitric oxide
        • sildenafil
          Sildenafil
          Sildenafil citrate, sold as Viagra, Revatio and under various other trade names, is a drug used to treat erectile dysfunction and pulmonary arterial hypertension . It was originally developed by British scientists and then brought to market by the US-based pharmaceutical company Pfizer...

           (Viagra)
        • tadalafil
          Tadalafil
          Tadalafil is a PDE5 inhibitor, currently marketed in pill form for treating erectile dysfunction under the name Cialis; and under the name Adcirca for the treatment of pulmonary arterial hypertension...

        • vardenafil
          Vardenafil
          Vardenafil is a PDE5 inhibitor used for treating erectile dysfunction that is sold under the trade names Levitra and Staxyn.-History:...

    • tetrahydrocannabinol
      Tetrahydrocannabinol
      Tetrahydrocannabinol , also known as delta-9-tetrahydrocannabinol , Δ1-THC , or dronabinol, is the main chemical psychoactive substance found in the cannabis plant. It was first isolated in 1964. In pure form, it is a glassy solid when cold, and becomes viscous and sticky if warmed...

       (THC) - the major active chemical in marijuana
      Medical cannabis
      Medical cannabis refers to the use of parts of the herb cannabis as a physician-recommended form of medicine or herbal therapy, or to synthetic forms of specific cannabinoids such as THC as a physician-recommended form of medicine...

      , its mild vasodilating effects redden the eyes of cannabis
      Cannabis (drug)
      Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...

       users.
    • theobromine
      Theobromine
      Theobromine , also known as xantheose, is a bitter alkaloid of the cacao plant, with the chemical formula C7H8N4O2. It is found in chocolate, as well as in a number of other foods, including the leaves of the tea plant, and the kola nut...

    • papaverine
      Papaverine
      Papaverine is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasm, vasospasm , and occasionally in the treatment of erectile dysfunction...

       an alkaloid found in the opium poppy papaver somniferum
    • estrogen
      Estrogen
      Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...


    Therapeutic uses

    Vasodilators are used to treat conditions such as hypertension
    Hypertension
    Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

    , where the patient has an abnormally high blood pressure, as well as angina and congestive heart failure
    Congestive heart failure
    Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...

    , where maintaining a lower blood pressure reduces the patient's risk of developing other cardiac problems.
    Flushing
    Flushing (physiology)
    For a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or...

     may be a physiological response to vasodilators. Viagra, a phosphodiesterase
    Phosphodiesterase
    A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...

     inhibitor, works to increase blood flow in the penis through vasodilation. It may also be used to treat pulmonary arterial hypertension (PAH).
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