Thromboxane-A synthase
Thromboxane A synthase 1 known as TBXAS1, is a cytochrome P450 enzyme that, in humans, is encoded by the TBXAS1 gene. This gene encodes a member of the cytochrome P450 superfamily of enzymes; the cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity; this endoplasmic reticulum membrane protein catalyzes the conversion of prostaglandin H2 to thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation and 12-Hydroxyheptadecatrienoic acid and agonist of Leukotriene B4 receptors and mediator of certain BLT2 receptor]] actions. The enzyme plays a role in several pathophysiological processes including hemostasis, cardiovascular disease, stroke; the gene expresses two transcript variants. Thromboxane synthase inhibitors are used as antiplatelet drugs.
Ifetroban is a selective thromboxane receptor antagonist. Dipyridamole antagonizes this receptor too, but has various other mechanisms of antiplatelet activity as well. Picotamide has activity both as a thromboxane synthase inhibitor and as a thromboxane receptor antagonist; the human thromboxane A synthase is a 60 kDa protein with 533 amino acids and a heme prosthetic group. This enzyme, anchored to the endoplasmic reticulum, is found in platelets and several other cell types; the NH2 terminus contains two hydrophobic segments whose secondary structure is believed to be helical. Evidence suggests. Moreover, the study of cDNA clones made possible by polymerase chain reaction techniques has further elucidated the TXA synthase’s primary structure. Similar to other members in the cytochrome P450 family, TXA synthase has a heme group coordinated to the thiolate group of a cysteine residue cysteine 480. Mutagenesis studies that made substitutions at that position resulted in loss of catalytic activity and minimal heme binding.
Other residues that had similar results were W133, R478, N110, R413. Located near the heme propionate groups or the distal face of the heme, these residues are important for proper integration of heme into the apoprotein. Researchers have found it difficult to obtain a crystal structure of TXA synthase due to the requirement of detergent treatment extraction from the membrane but they have utilized homology modeling to create a 3D structure. One model showed an alpha-helix-rich domain and a beta-sheet-rich domain; the heme was found to be sandwiched between helices I and L. Thromboxane A is derived from the prostaglandin H2 molecule. PGH2 contains a weak epidioxy bond, a possible mechanism is known to involve homolytic cleavage of the epidioxide and a rearrangement to TXA. A heme group in the active site of TXA synthase plays an important role in the mechanism. Stopped-flow kinetic studies with a substrate analog and recombinant TXA synthase revealed that substrate binding occurs in two steps.
First, there is a fast initial binding to the protein and a subsequent ligation to the heme iron. In the first step of the mechanism, the heme iron coordinates to the C-9 endoperoxide oxygen, it participates in homolytic cleavage of the O-O bond in the endoperoxide, which represents the rate-limiting step, undergoes a change in redox state from Fe to Fe. A free oxygen radical forms at C-11, this intermediate undergoes ring cleavage. With the free radical now at C-12, the iron heme oxidizes this radical to a carbocation; the molecule is now ready for intramolecular ring formation. The negatively charged oxygen attacks the carbonyl, the electrons from one of the double bonds are drawn to the carbocation, thus closing the ring. Maintaining a balance between prostacyclins and thromboxanes is important in the body because these two eicosanoids exert opposing effects. In catalyzing the synthesis of thromboxanes, TXA synthase is involved in a flux pathway that can modulate the amount of thromboxane produced.
This control becomes an important factor in several processes, such as blood pressure regulation and inflammatory responses. Dysregulation of TXA synthase and an imbalance in the prostacyclin-thromboxane ratio are thought to underlie many pathological conditions, such as pulmonary hypertension; because thromboxanes play a role in vasoconstriction and platelet aggregation, their dominance can disrupt vascular homeostasis and cause thrombotic vascular events. Furthermore, the importance of thromboxanes and their synthases in vascular homeostasis is illustrated by findings that patients whose platelets were unresponsive to TXA displayed hemostatic defects and that a deficiency of platelet TXA production led to bleeding disorders. Furthermore, it has been found that the expression of TXA synthase may be of critical importance to the development and progression of cancer. An overall increase in TXA synthase expression has been observed in a variety of cancers, such as papillary thyroid carcinoma, prostate cancer, renal cancer.
Cancer cells are known for their limitless cellular replicative potential, it has been hypothesized that changes in eicosanoid profile affect cancer growth. Research has led to the proposal that TXA synthase contributes to a range of tumor survival pathways, including growth, apoptosis inhibition and metastasis. Prostanoid 12-Hydroxyheptadecatrienoic acid Thromboxane-A+Synthase at the US National Library of Medicine Medical Subject Headings
Lipid
In biology and biochemistry, a lipid is a biomolecule, soluble in nonpolar solvents. Non-polar solvents are hydrocarbons used to dissolve other occurring hydrocarbon lipid molecules that do not dissolve in water, including fatty acids, sterols, fat-soluble vitamins, diglycerides and phospholipids; the functions of lipids include storing energy and acting as structural components of cell membranes. Lipids have applications in the food industries as well as in nanotechnology. Scientists sometimes broadly define lipids as amphiphilic small molecules. Biological lipids originate or in part from two distinct types of biochemical subunits or "building-blocks": ketoacyl and isoprene groups. Using this approach, lipids may be divided into eight categories: fatty acids, glycerophospholipids, sphingolipids and polyketides. Although the term "lipid" is sometimes used as a synonym for fats, fats are a subgroup of lipids called triglycerides. Lipids encompass molecules such as fatty acids and their derivatives, as well as other sterol-containing metabolites such as cholesterol.
Although humans and other mammals use various biosynthetic pathways both to break down and to synthesize lipids, some essential lipids can't be made this way and must be obtained from the diet. In 1815, Henry Braconnot classified lipids in two categories and huiles. In 1823, Michel Eugène Chevreul developed a more detailed classification, including oils, tallow, resins and volatile oils. In 1827, William Prout recognized fat, along with protein and carbohydrate, as an important nutrient for humans and animals. For a century, chemists regarded "fats" as only simple lipids made of fatty acids and glycerol, but new forms were described later. Theodore Gobley discovered phospholipids in mammalian brain and hen egg, called by him as "lecithins". Thudichum discovered in human brain some phospholipids and sphingolipids; the terms lipoid, lipin and lipid have been used with varied meanings from author to author. In 1912, Rosenbloom and Gies proposed the substitution of "lipoid" by "lipin". In 1920, Bloor introduced a new classification for "lipoids": simple lipoids, compound lipoids, the derived lipoids.
The word "lipid", which stems etymologically from the Greek lipos, was introduced in 1923 by Gabriel Bertrand. Bertrands included in the concept not only the traditional fats, but the "lipoids", with a complex constitution. In 1947, T. P. Hilditch divided lipids into "simple lipids", with greases and waxes, "complex lipids", with phospholipids and glycolipids. Fatty acids, or fatty acid residues when they are part of a lipid, are a diverse group of molecules synthesized by chain-elongation of an acetyl-CoA primer with malonyl-CoA or methylmalonyl-CoA groups in a process called fatty acid synthesis, they are made of a hydrocarbon chain. The fatty acid structure is one of the most fundamental categories of biological lipids, is used as a building-block of more structurally complex lipids; the carbon chain between four and 24 carbons long, may be saturated or unsaturated, may be attached to functional groups containing oxygen, halogens and sulfur. If a fatty acid contains a double bond, there is the possibility of either a cis or trans geometric isomerism, which affects the molecule's configuration.
Cis-double bonds cause the fatty acid chain to bend, an effect, compounded with more double bonds in the chain. Three double bonds in 18-carbon linolenic acid, the most abundant fatty-acyl chains of plant thylakoid membranes, render these membranes fluid despite environmental low-temperatures, makes linolenic acid give dominating sharp peaks in high resolution 13-C NMR spectra of chloroplasts; this in turn plays an important role in the function of cell membranes. Most occurring fatty acids are of the cis configuration, although the trans form does exist in some natural and hydrogenated fats and oils. Examples of biologically important fatty acids include the eicosanoids, derived from arachidonic acid and eicosapentaenoic acid, that include prostaglandins and thromboxanes. Docosahexaenoic acid is important in biological systems with respect to sight. Other major lipid classes in the fatty acid category are the fatty esters and fatty amides. Fatty esters include important biochemical intermediates such as wax esters, fatty acid thioester coenzyme A derivatives, fatty acid thioester ACP derivatives and fatty acid carnitines.
The fatty amides include N-acyl ethanolamines, such as the cannabinoid neurotransmitter anandamide. Glycerolipids are composed of mono-, di-, tri-substituted glycerols, the best-known being the fatty acid triesters of glycerol, called triglycerides; the word "triacylgl
Ether
Ethers are a class of organic compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula R -- O -- R ′, where R ′ represent the alkyl or aryl groups. Ethers can again be classified into two varieties: if the alkyl groups are the same on both sides of the oxygen atom it is a simple or symmetrical ether, whereas if they are different, the ethers are called mixed or unsymmetrical ethers. A typical example of the first group is the solvent and anesthetic diethyl ether referred to as "ether". Ethers are common in organic chemistry and more prevalent in biochemistry, as they are common linkages in carbohydrates and lignin. Ethers feature C–O–C linkage defined by a bond angle of about 110° and C–O distances of about 140 pm; the barrier to rotation about the C–O bonds is low. The bonding of oxygen in ethers and water is similar. In the language of valence bond theory, the hybridization at oxygen is sp3. Oxygen is more electronegative than carbon, thus the hydrogens alpha to ethers are more acidic than in simple hydrocarbons.
They are far less acidic than hydrogens alpha to carbonyl groups, however. Depending on the groups at R and R′, ethers are classified into two types:Simple ethers or symmetrical ethers. Mixed ethers or asymmetrical ethers. In the IUPAC nomenclature system, ethers are named using the general formula "alkoxyalkane", for example CH3–CH2–O–CH3 is methoxyethane. If the ether is part of a more-complex molecule, it is described as an alkoxy substituent, so –OCH3 would be considered a "methoxy-" group; the simpler alkyl radical is written in front, so CH3–O–CH2CH3 would be given as methoxyethane. IUPAC rules are not followed for simple ethers; the trivial names for simple ethers are a composite of the two substituents followed by "ether". For example, ethyl methyl ether, diphenylether; as for other organic compounds common ethers acquired names before rules for nomenclature were formalized. Diethyl ether is called "ether", but was once called sweet oil of vitriol. Methyl phenyl ether is anisole, because it was found in aniseed.
The aromatic ethers include furans. Acetals are another class of ethers with characteristic properties. Polyethers are compounds with more than one ether group; the crown ethers are examples of small polyethers. Some toxins produced by dinoflagellates such as brevetoxin and ciguatoxin are large and are known as cyclic or ladder polyethers. Polyether refers to polymers which contain the ether functional group in their main chain; the term glycol is reserved for low to medium range molar mass polymer when the nature of the end-group, a hydroxyl group, still matters. The term "oxide" or other terms are used for high molar mass polymer when end-groups no longer affect polymer properties; the phenyl ether polymers are a class of aromatic polyethers containing aromatic cycles in their main chain: Polyphenyl ether and Poly. Many classes of compounds with C–O–C linkages are not considered ethers: Esters, carboxylic acid anhydrides. Ether molecules cannot form hydrogen bonds with each other, resulting in low boiling points compared to those of the analogous alcohols.
The difference in the boiling points of the ethers and their isomeric alcohols becomes lower as the carbon chains become longer, as the van der Waals interactions of the extended carbon chain dominates over the presence of hydrogen bonding. Ethers are polar; the C–O–C bond angle in the functional group is about 110°, the C–O dipoles do not cancel out. Ethers are more polar than alkenes but not as polar as alcohols, esters, or amides of comparable structure; the presence of two lone pairs of electrons on the oxygen atoms makes hydrogen bonding with water molecules possible. Cyclic ethers such as tetrahydrofuran and 1,4-dioxane are miscible in water because of the more exposed oxygen atom for hydrogen bonding as compared to linear aliphatic ethers. Other properties are: The lower ethers are volatile and flammable. Lower ethers act as anaesthetics. Ethers are good organic solvents. Simple ethers are tasteless. Ethers are quite stable chemical compounds which do not react with bases, active metals, dilute acids, oxidising agents, reducing agents.
They are of low chemical reactivity, but they are more reactive than alkanes. Epoxides and acetals are unrepresentative classes of ethers and are discussed in separate articles. Important reactions are listed below. Although ethers resist hydrolysis, their polar bonds are cloven by mineral acids such as hydrobromic acid and hydroiodic acid. Hydrogen chloride cleaves ethers only slowly. Methyl ethers afford methyl halides: ROCH3 + HBr → CH3Br + ROHThese reactions proceed via onium intermediates, i.e. +Br−. Some ethers undergo rapid cleavage with boron tribromide to give the alkyl bromide. Depending on the substituents, some ethers can be cloven with a variety of reagents, e.g. strong base. When stored in the presence of air or oxygen, ethers tend to form explosive peroxides, such as diethyl ether peroxide; the reaction is accelerated by light, metal catalysts, aldehydes. In addition to avoiding storage conditions to form peroxides, it is recommended, when an ether is used as a solvent, not to distill it to dryness, as any peroxides that may have formed, being less volatil
G protein
G proteins known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their activity is regulated by factors that control their ability to bind to and hydrolyze guanosine triphosphate to guanosine diphosphate; when they are bound to GTP, they are'on', when they are bound to GDP, they are'off'. G proteins belong to the larger group of enzymes called GTPases. There are two classes of G proteins; the first function as monomeric small GTPases, while the second function as heterotrimeric G protein complexes. The latter class of complexes is made up of alpha and gamma subunits. In addition, the beta and gamma subunits can form a stable dimeric complex referred to as the beta-gamma complex. Heterotrimeric G proteins located within the cell are activated by G protein-coupled receptors that span the cell membrane. Signaling molecules bind to a domain of the GPCR located outside the cell, an intracellular GPCR domain in turn activates a particular G protein.
Some inactive-state GPCRs have been shown to be "pre-coupled" with G proteins. The G protein activates a cascade of further signaling events that results in a change in cell function. G protein-coupled receptor and G proteins working together transmit signals from many hormones, neurotransmitters, other signaling factors. G proteins regulate metabolic enzymes, ion channels, transporter proteins, other parts of the cell machinery, controlling transcription, motility and secretion, which in turn regulate diverse systemic functions such as embryonic development and memory, homeostasis. G proteins were discovered when Alfred G. Gilman and Martin Rodbell investigated stimulation of cells by adrenaline, they found that when adrenaline binds to a receptor, the receptor does not stimulate enzymes directly. Instead, the receptor stimulates a G protein, which stimulates an enzyme. An example is adenylate cyclase, which produces the second messenger cyclic AMP. For this discovery, they won the 1994 Nobel Prize in Medicine.
Nobel prizes have been awarded for many aspects of signaling by G GPCRs. These include receptor antagonists, neurotransmitters, neurotransmitter reuptake, G protein-coupled receptors, G proteins, second messengers, the enzymes that trigger protein phosphorylation in response to cAMP, consequent metabolic processes such as glycogenolysis. Prominent examples include: The 1947 Nobel Prize in Physiology or Medicine to Carl Cori, Gerty Cori and Bernardo Houssay, for their discovery of how glycogen is broken down to glucose and resynthesized in the body, for use as a store and source of energy. Glycogenolysis is stimulated by numerous neurotransmitters including adrenaline; the 1970 Nobel Prize in Physiology or Medicine to Julius Axelrod, Bernard Katz and Ulf von Euler for their work on the release and reuptake of neurotransmitters. The 1971 Nobel Prize in Physiology or Medicine to Earl Sutherland for discovering the key role of adenylate cyclase, which produces the second messenger cyclic AMP; the 1988 Nobel Prize in Physiology or Medicine to George H. Hitchings, Sir James Black and Gertrude Elion "for their discoveries of important principles for drug treatment" targeting GPCRs.
The 1992 Nobel Prize in Physiology or Medicine to Edwin G. Krebs and Edmond H. Fischer for describing how reversible phosphorylation works as a switch to activate proteins, to regulate various cellular processes including glycogenolysis; the 1994 Nobel Prize in Physiology or Medicine to Alfred G. Gilman and Martin Rodbell for their discovery of "G-proteins and the role of these proteins in signal transduction in cells"; the 2000 Nobel Prize in Physiology or Medicine to Eric Kandel, Arvid Carlsson and Paul Greengard, for research on neurotransmitters such as dopamine, which act via GPCRs. The 2004 Nobel Prize in Physiology or Medicine to Richard Axel and Linda B. Buck for their work on G protein-coupled olfactory receptors; the 2012 Nobel Prize in Chemistry to Brian Kobilka and Robert Lefkowitz for their work on GPCR function. G proteins are important signal transducing molecules in cells. "Malfunction of GPCR signaling pathways are involved in many diseases, such as diabetes, allergies, cardiovascular defects, certain forms of cancer.
It is estimated that about 30% of the modern drugs' cellular targets are GPCRs." The human genome encodes 800 G protein-coupled receptors, which detect photons of light, growth factors and other endogenous ligands. 150 of the GPCRs found in the human genome have still-unknown functions. Whereas G proteins are activated by G protein-coupled receptors, they are inactivated by RGS proteins. Receptors stimulate GTP binding. RGS proteins stimulate GTP hydrolysis. All eukaryotes has evolved a large diversity of G proteins. For instance, humans encode 18 different Gα proteins, 5 Gβ proteins, 12 Gγ proteins. G protein can refer to two distinct families of proteins. Heterotrimeric G proteins, sometimes referred to as the "large" G proteins, are activated by G protein-coupled receptors and are made up of alpha and gamma subunits. "Small" G proteins belong to the Ras superfamily of small GTPases. These proteins are homologous to the alpha subunit found in heterotrimers, but are in fact monomeric, consisting of only a single unit.
However, like their larger relatives, they al
Fibrinogen
Fibrinogen is a glycoprotein that circulates in the blood of vertebrates. During tissue and vascular injury it is converted enzymatically by thrombin to fibrin and subsequently to a fibrin-based blood clot. Fibrinogen functions to occlude blood vessels and thereby stop excessive bleeding. However, fibrinogen's product, fibrin and reduces the activity of thrombin; this activity, sometimes referred to as antithrombin I, serves to limit blood clotting. Loss or reduction in this antithrombin 1 activity due to mutations in fibrinogen genes or hypo-fibrinogen conditions can lead to excessive blood clotting and thrombosis. Fibrin mediates blood platelet and endothelial cell spreading, tissue fibroblast proliferation, capillary tube formation, angiogenesis and thereby functions to promote tissue revascularization, wound healing, tissue repair. Reduced and/or dysfunctional fibrinogens occur in various congenital and acquired human fibrinogen-related disorders; these disorders represent a clinically important group of rare conditions in which individuals may present with severe episodes of pathological bleeding and thrombosis.
Certain of these disorders may be the cause of liver and kidney diseases. Fibrinogen is a "positive" acute-phase protein, i.e. its blood levels rise in response to systemic inflammation, tissue injury, certain other events. It is elevated in various cancers. Elevated levels of fibrinogen in inflammation as well as cancer and other conditions have been suggested to be the cause of thrombosis and vascular injury that accompanies these conditions. Fibrinogen is made and secreted into the blood by liver hepatocyte cells. Endothelium cells are reported to make what appears to be small amounts of fibrinogen but this fibrinogen has not been characterized; the final secreted, hepatocyte-derived glycoprotein is composed of two trimers with each trimer composed of three different polypeptide chains, the fibrinogen alpha chain encoded by the FGA gene, the fibrinogen beta chain encoded by the FGB gene, the fibrinogen gamma chain encoded by the FGG gene. All three genes are located on the long or "p" arm of human chromosome 4.
Alternate splicing of the FGA gene produces a minor expanded isoform of Aα termed AαE which replaces Aα in 1–3% of circulating fibrinogen. Hence, the final fibrinogen product is composed principally of Aα, Bβ, γ chains with a small percentage of it containing AαE and/or γ' chains in place of Aα and/or γ chains, respectively; the three genes are transcribed and translated in co-ordination by a mechanism which remains incompletely understood. The coordinated transcription of these three fibrinogen genes is and increased by systemic conditions such as inflammation and tissue injury. Cytokines produced during these systemic conditions, such as interleukin 6 and interleukin 1β, appear responsible for up-regulating this transcription; the Aα, Bβ, γ chains are transcribed and translated coordinately on the endoplasmic reticulum with their peptide chains being passed into the ER while their signal peptide portions are removed. Inside the ER, the three chains are assembled into Aαγ and Bβγ dimers to AαBβγ trimers, to 2 heximers, i.e. two AαBβγ trimers joined together by numerous disulfide bonds.
The heximer is transferred to the Golgi where it is glycosylated, hydroxylated and phosphorylated to form the mature fibrinogen glycoprotein, secreted into the blood. Mature fibrinogen is arranged as a long flexible protein array of three nodules held together by a thin thread, estimated to have a diameter between 8 and 15 Angstrom; the two end nodules are alike in consisting of Bβ and γ chains while the center smaller nodule consists of two intertwined Aα alpha chains. Measurements of shadow lengths indicate that nodule diameters are in the range 50 to 70 Å; the length of the dried molecule is 475 ± 25 Å. The fibrinogen molecule circulates as a soluble plasma glycoprotein with a typical molecular weight of ~340 kDa, it has a rod-like shape with dimensions of 9 × 47.5 × 6 nm and has a negative net charge at physiological pH. The normal concentration of fibrinogen in blood plasma is 150–400 mg/dL with levels appreciably below or above this range associated with pathological bleeding and/or thrombosis.
Fibrinogen has a circulating half-life of ~4 days. During blood clotting, thrombin attacks the N-terminus of the Aα and Bβ chains in fibrinogen to form individual fibrin strands plus two small polypeptides, fibrinopeptides a and b derived from these respective chains; the individual fibrin strands polymerize and are cross-linked with other fibrin stands by blood factor XIIIa to form an extensive interconnected fibrin network, the basis for the formation of a mature fibrin clot. In addition to forming fibrin, fibrinogen promotes blood clotting by forming bridges between, activating, blood platelets through binding to their GpIIb/IIIa surface membrane fibrinogen receptor. Fibrin participates in limiting blood clot formation and lysing formed blood
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of the widening of blood vessels; the process is important in staunching hemorrhage and acute blood loss. When blood vessels constrict, the flow of blood is restricted or decreased, thus retaining body heat or increasing vascular resistance; this makes the skin turn paler because less blood reaches the surface, reducing the radiation of heat. On a larger level, vasoconstriction is one mechanism by which the body regulates and maintains mean arterial pressure. Medications causing vasoconstriction known as vasoconstrictors, are one type of medicine used to raise blood pressure. Generalized vasoconstriction results in an increase in systemic blood pressure, but it may occur in specific tissues, causing a localized reduction in blood flow; the extent of vasoconstriction may be severe depending on the substance or circumstance.
Many vasoconstrictors cause pupil dilation. Medications that cause vasoconstriction include: antihistamines and stimulants. Severe vasoconstriction may result in symptoms of intermittent claudication; the mechanism that leads to vasoconstriction results from the increased concentration of calcium within vascular smooth muscle cells. However, the specific mechanisms for generating an increased intracellular concentration of calcium depends on the vasoconstrictor. Smooth muscle cells are capable of generating action potentials, but this mechanism is utilized for contraction in the vasculature. Hormonal or pharmacokinetic components are more physiologically relevant. Two common stimuli for eliciting smooth muscle contraction are circulating epinephrine and activation of the sympathetic nervous system that directly innervates the muscle; these compounds interact with cell surface adrenergic receptors. Such stimuli result in a signal transduction cascade that leads to increased intracellular calcium from the sarcoplasmic reticulum through IP3-mediated calcium release, as well as enhanced calcium entry across the sarcolemma through calcium channels.
The rise in intracellular calcium complexes with calmodulin, which in turn activates myosin light-chain kinase. This enzyme is responsible for phosphorylating the light chain of myosin to stimulate cross-bridge cycling. Once elevated, the intracellular calcium concentration is returned to its normal concentration through a variety of protein pumps and calcium exchangers located on the plasma membrane and sarcoplasmic reticulum; this reduction in calcium removes the stimulus necessary for contraction, allowing for a return to baseline. Factors that trigger vasoconstriction can be of endogenous origin. Ambient temperature is an example of the former. Cutaneous vasoconstriction will occur because of the body's exposure to the severe cold. Examples of endogenous factors include the autonomic nervous system, circulating hormones, intrinsic mechanisms inherent to the vasculature itself. Examples include stimulants, amphetamines and cocaine. Many are used in medicine to treat hypotension and as topical decongestants.
Vasoconstrictors are used clinically to increase blood pressure or to reduce local blood flow. Vasoconstrictors mixed with local anesthetics are used to increase the duration of local anesthesia by constricting the blood vessels, thereby safely concentrating the anesthetic agent for an extended duration, as well as reducing hemorrhage; the routes of administration vary. They may be both topical. For example, pseudoephedrine is taken orally and phenylephrine is topically applied to the nasal passages or eyes. Examples include: Vasoconstriction is a procedure of the body that averts orthostatic hypotension, it is a part of a body negative feedback loop. For example, vasoconstriction is a hypothermic preventative in which the blood vessels constrict and blood must move at a higher pressure to prevent a hypoxic reaction. ATP is used as a form of energy to increase this pressure to heat the body. Once homeostasis is restored, the blood pressure and ATP production regulates. Vasoconstriction occurs in superficial blood vessels of warm-blooded animals when their ambient environment is cold.
Vasoconstriction can be a contributing factor to erectile dysfunction. An increase in blood flow to the penis causes an erection. Improper vasoconstriction may play a role in secondary hypertension. Addison's disease Inotrope Hypertension Nitric oxide Pheochromocytoma Shock Vasodilation Postural orthostatic tachycardia syndrome Hemostasis Definition of Vasoconstriction on HealthScout Cannabis arteritis revisited--ten new case reports Are coronary heart disease and peripheral arterial disease associated with tobacco or cannabis consumption Vasoconstrictor effects of Cannabis appear to inhibit Migraine attacks
