Mammalian vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin,
is a
hormone
A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
synthesized from the
''AVP'' gene as a
peptide
Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...
prohormone
A prohormone is a committed precursor of a hormone consisting of peptide hormones synthesized together that has a minimal hormonal effect by itself because of its expression-suppressing structure, often created by protein folding and binding addit ...
in
neuron
A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...
s in the
hypothalamus
The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
,
and is converted to AVP. It then travels down the
axon
An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...
terminating in the
posterior pituitary
The posterior pituitary (or neurohypophysis) is the posterior lobe of the pituitary gland which is part of the endocrine system. Unlike the anterior pituitary, the posterior pituitary is not glandular, but largely a collection of axonal projec ...
, and is released from
vesicles
Vesicle may refer to:
; In cellular biology or chemistry
* Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane
* Synaptic vesicle
In a neuron, synaptic vesicles (or neurotransmitter vesicles) s ...
into the circulation in response to extracellular fluid
hypertonicity (
hyperosmolality). AVP has two primary functions. First, it increases the amount of solute-free water reabsorbed back into the
circulation from the filtrate in the
kidney tubules of the
nephron
The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structu ...
s. Second, AVP constricts
arteriole
An arteriole is a small-diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillary, capillaries.
Arterioles have vascular smooth muscle, muscular walls (usually only one to two layers of smoo ...
s, which increases
peripheral vascular resistance and raises arterial
blood pressure
Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...
.
A third function is possible. Some AVP may be released directly into the
brain
The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
from the hypothalamus, and may play an important role in
social behavior
Social behavior is behavior among two or more organisms within the same species, it encompasses any behavior in which one member affects another. Social behavior can be seen as similar to an exchange of goods, with the expectation that when you ...
,
sexual motivation and
pair bond
In biology, a pair bond is the strong affinity that develops in some species between a mating pair, often leading to the production and rearing of young and potentially a lifelong bond. Pair-bonding is a term coined in the 1940s that is frequently ...
ing, and maternal responses to stress.
Vasopressin induces differentiation of stem cells into
cardiomyocytes
Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of ...
and promotes heart muscle homeostasis.
It has a very short half-life, between 16 and 24 minutes.
Physiology
Function
Vasopressin regulates the
tonicity
In chemical biology, tonicity is a measure of the effective osmotic pressure gradient; the water potential of two Solution (chemistry), solutions separated by a Semipermeable membrane, partially-permeable cell Cell membrane, membrane. Tonicity ...
of body fluids. It is released from the posterior pituitary in response to
hypertonicity and causes the kidneys to reabsorb solute-free water and return it to the circulation from the tubules of the nephron, thus returning the tonicity of the body fluids toward normal. An incidental consequence of this renal reabsorption of water is concentrated
urine
Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
and reduced urine volume. AVP released in high concentrations may also raise blood pressure by inducing moderate
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 vasodilation, the widening of blood vesse ...
.
AVP also may have a variety of neurological effects on the brain. It may influence pair-bonding in
voles
Voles are small rodents that are relatives of lemmings and hamsters, but with a stouter body; a longer, hairy tail; a slightly rounder head; smaller eyes and ears; and differently formed molar (tooth), molars (high-crowned with angular cusps i ...
. The high-density distributions of vasopressin receptor AVPr1a in
prairie vole
The prairie vole (''Microtus ochrogaster'') is a small vole found in central North America.
Description
The vole has long, coarse grayish-brown fur on the upper portion of the body and yellowish fur on the lower portion of the body. It has sh ...
ventral forebrain regions have been shown to facilitate and coordinate reward circuits during partner preference formation, critical for pair bond formation.
A very similar substance, ''lysine vasopressin'' (LVP) or lypressin, has the same function in
pig
The pig (''Sus domesticus''), also called swine (: swine) or hog, is an omnivorous, domesticated, even-toed, hoofed mammal. It is named the domestic pig when distinguishing it from other members of the genus '' Sus''. Some authorities cons ...
s and its synthetic version was used in human AVP deficiency, although it has been largely replaced by
desmopressin
Desmopressin, sold under the trade name DDAVP among others, is a medication used to treat diabetes insipidus, bedwetting, hemophilia A, von Willebrand disease, and high blood urea levels. In hemophilia A and von Willebrand disease, it should ...
.
Kidney
Vasopressin has three main effects which are:
# Increasing the water permeability of distal convoluted tubule (DCT) and cortical collecting tubules (CCT), as well as outer and inner medullary collecting duct (OMCD & IMCD) in the kidney, thus allowing water reabsorption and excretion of more concentrated urine, i.e.,
antidiuresis. This occurs through increased transcription and insertion of water channels (
Aquaporin-2) into the
apical membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extra ...
of collecting tubule and collecting duct epithelial cells. Aquaporins allow water to move down their osmotic gradient and out of the nephron, increasing the amount of water re-absorbed from the filtrate (forming urine) back into the bloodstream. This effect is mediated by
V2 receptors. Vasopressin also increases the concentration of calcium in the collecting duct cells, by episodic release from intracellular stores. Vasopressin, acting through
cAMP
Camp may refer to:
Areas of confinement, imprisonment, or for execution
* Concentration camp, an internment camp for political prisoners or politically targeted demographics, such as members of national or minority ethnic groups
* Extermination ...
, also increases transcription of the aquaporin-2 gene, thus increasing the total number of aquaporin-2 molecules in collecting duct cells.
# Increasing permeability of the inner medullary portion of the collecting duct to
urea
Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest am ...
by regulating the cell surface expression of
urea transporter
A urea transporter is a membrane transport protein, transporting urea. Humans and other mammals have two types of urea transport proteins, UT-A and UT-B. The UT-A proteins are important for renal urea handling and are produced by alternative spl ...
s,
which facilitates its reabsorption into the
medullary interstitium as it travels down the concentration gradient created by removing water from the
connecting tubule
The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct participates in electrolyte and fluid balance through rea ...
,
cortical collecting duct
The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct participates in electrolyte and fluid balance through reabsor ...
, and
outer medullary collecting duct.
# Acute increase of
sodium
Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...
absorption across the ascending
loop of Henle
In the kidney, the loop of Henle () (or Henle's loop, Henle loop, nephron loop or its Latin counterpart ''ansa nephroni'') is the portion of a nephron that leads from the proximal convoluted tubule to the distal convoluted tubule. Named after it ...
. This adds to the
countercurrent multiplication
Countercurrent may refer to:
*Countercurrent pool
*Countercurrent exchange
*Countercurrent chromatography
*Equatorial Counter Current
*''Counter-Currents'', an alt-right online publication
*''Countercurrents.org'', an Indian news website
*two polit ...
which aids in proper water reabsorption later in the
distal tubule
The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule.
Physiology
It is partly responsible for the regulation of potassium, sodium, calcium, and pH.
On its Apical membrane, apica ...
and
collecting duct
The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct participates in electrolyte and fluid balance through rea ...
.
The hormone vasopressin also stimulates the activity of
NKCC2. Vasopressin stimulates sodium chloride reabsorption in the thick ascending limb of the nephron by activating signaling pathways. Vasopressin increases the traffic of NKCC2 to the membrane and phosphorylates some
serine
Serine
(symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − ...
and
threonine
Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form when dissolved in water), a carboxyl group (which is in the deprotonated −COO− ...
sites on the cytoplasmic N-terminal of the NKCC2 located in the membrane, increasing its activity. Increased NKCC2 activity aids in water reabsorption in the collecting duct through
aquaporin 2
Aquaporin-2 (AQP-2) is found in the apical cell membranes of the kidney's collecting duct principal cells and in intracellular vesicles located throughout the cell. It is encoded by the gene.
Regulation
It is the only aquaporin regulated b ...
channels by creating a hypo-osmotic filtrate.
Central nervous system
Vasopressin released within the brain may have several actions:
* Vasopressin is released into the brain in a
circadian rhythm
A circadian rhythm (), or circadian cycle, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism (i.e., Endogeny (biology), endogenous) and responds to the env ...
by neurons of the
suprachiasmatic nucleus
The suprachiasmatic nucleus or nuclei (SCN) is a small region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for regulating sleep cycles in animals. Reception of light inputs from photosensitive r ...
.
* Vasopressin released from posterior pituitary is associated with nausea.
* Recent evidence suggests that vasopressin may have analgesic effects. The analgesia effects of vasopressin were found to be dependent on both stress and sex.
Regulation
Gene regulation
Vasopressin is regulated by
''AVP'' gene expression which is managed by major clock controlled genes. In this circadian circuit known as the
transcription-translation feedback loop (TTFL),
Per2
PER2 is a protein in mammals encoded by the ''PER2'' gene. ''PER2'' is noted for its major role in circadian rhythms.
Discovery
The ''per ''gene'' ''was first discovered using forward genetics in '' Drosophilla melanogaster'' in 1971. Mammali ...
protein accumulates and is phosphorylated by
CK1E. Per2 subsequently inhibits the transcription factors
Clock
A clock or chronometer is a device that measures and displays time. The clock is one of the oldest Invention, human inventions, meeting the need to measure intervals of time shorter than the natural units such as the day, the lunar month, a ...
and
BMAL1
Basic helix-loop-helix ARNT-like protein 1 or aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL), or brain and muscle ARNT-like 1 is a protein that in humans is encoded by the ''BMAL1'' gene on chromosome 11, region p15.3. It's ...
in order to reduce Per2 protein levels in the cell. At the same time, Per2 also inhibits the transcription factors for the ''AVP'' gene in order to regulate its expression, the expression of vasopressin, and other ''AVP'' gene products.
Many factors influence the secretion of vasopressin:
*
Ethanol
Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...
(alcohol) reduces the calcium-dependent secretion of AVP by blocking voltage-gated calcium channels in neurohypophyseal nerve terminals in rats.
*
Angiotensin
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adr ...
II stimulates AVP secretion, in keeping with its general pressor and pro-volumic effects on the body.
*
Atrial natriuretic peptide
Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the ''NPPA'' gene. Natriuretic peptides (ANP, BNP, and CNP) are a family of ho ...
inhibits AVP secretion, in part by inhibiting Angiotensin II-induced stimulation of AVP secretion.
*
Cortisol
Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone.
Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...
inhibits secretion of antidiuretic hormone.
Production and secretion
The physiological stimulus for secretion of vasopressin is increased osmolality of the plasma, monitored by the hypothalamus. A decreased arterial
blood volume
Blood volume (volemia) is the volume of blood ( blood cells and plasma) in the circulatory system of any individual.
Humans
A typical adult has a blood volume of approximately 5 liters, with females and males having approximately the same blood p ...
, (such as can occur in
cirrhosis
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
,
nephrosis
Nephrosis is any of various forms of kidney disease (nephropathy). In an old and broad sense of the term, it is any nephropathy, but in current usage the term is usually restricted to a narrower sense of nephropathy without inflammation
I ...
, and
heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood.
Although symptoms vary based on which side of the heart is affected, HF ...
), stimulates secretion, even in the face of decreased osmolality of the plasma: it supersedes osmolality, but
with a milder effect. In other words, the unloading of
arterial baroreceptors when the arterial blood volume is low stimulates vasopressin secretion despite the presence of hypoosmolality (hyponatremia).
The AVP that is measured in peripheral blood is almost all derived from secretion from the
posterior pituitary gland
The posterior pituitary (or neurohypophysis) is the posterior lobe of the pituitary gland which is part of the endocrine system. Unlike the anterior pituitary, the posterior pituitary is not glandular, but largely a collection of axonal project ...
(except in cases of AVP-secreting tumours). Vasopressin is produced by
magnocellular neurosecretory neurons in the
paraventricular nucleus of hypothalamus
The paraventricular nucleus (PVN) is a nucleus in the hypothalamus, located next to the third ventricle. Many of its neurons project to the posterior pituitary where they secrete oxytocin, and a smaller amount of vasopressin. Other secretion ...
(PVN) and
supraoptic nucleus
The supraoptic nucleus (SON) is a nucleus of magnocellular neurosecretory cells in the hypothalamus of the mammalian brain. The nucleus is situated at the base of the brain, adjacent to the optic chiasm. In humans, the SON contains about 3,000 ...
(SON). It then travels down the axon through the
infundibulum An infundibulum (Latin for ''funnel''; plural, ''infundibula'') is a funnel-shaped cavity or organ.
Anatomy
* Brain: the pituitary stalk, also known as the ''infundibulum'' and ''infundibular stalk'', is the connection between the hypothalamus an ...
within neurosecretory granules that are found within Herring bodies, localized swellings of the axons and nerve terminals. These carry the peptide directly to the posterior pituitary gland, where it is stored until released into the blood.
There are other sources of AVP, beyond the hypothalamic magnocellular neurons. For example, AVP is also synthesized by
parvocellular neurosecretory neurons of the PVN, transported and released at the
median eminence
The median eminence is generally defined as the portion of the ventral hypothalamus from which the portal vessels arise. The median eminence is a small swelling on the tuber cinereum, posterior to and on top of the pituitary stalk; it lies in th ...
, from which it travels through the
hypophyseal portal system
The hypophyseal portal system is a system of blood vessels in the microcirculation at the base of the brain, connecting the hypothalamus with the anterior pituitary. Its main function is to quickly transport and exchange hormones between the hyp ...
to the anterior pituitary, where it stimulates
corticotropic cell
Corticotropic cells, (corticotropes or corticotrophs) are basophilic cells in the anterior pituitary that produce pro-opiomelanocortin (POMC) which undergoes cleavage to adrenocorticotropin (ACTH), β-lipotropin (β-LPH), and melanocyte-stimulat ...
s synergistically with CRH to produce ACTH (by itself it is a weak secretagogue).
Vasopressin during surgery and anaesthesia
Vasopressin concentration is used to measure
surgical stress
Surgical stress is the systemic response to surgical injury and is characterized by activation of the sympathetic nervous system, endocrine responses as well as immunological and haematological changes. Measurement of surgical stress is used in a ...
for evaluation of surgical techniques. Plasma vasopressin concentration is elevated by
noxious stimuli
A noxious stimulus is a stimulus strong enough to threaten the body's integrity (i.e. cause damage to tissue). Noxious stimulation induces peripheral afferents responsible for transducing pain (including A-delta and C- nerve fibers, as well a ...
, predominantly during abdominal surgery, especially at gut manipulation, traction of viscera, as well as abdominal insufflation with carbon dioxide during laparoscopic surgery.
Receptors
Types of AVP receptors and their actions:
Structure and relation to oxytocin
The vasopressins are
peptide
Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...
s consisting of nine
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
s (nonapeptides). The amino acid sequence of arginine vasopressin (argipressin) is
Cys-
Tyr-
Phe-
Gln-
Asn-
Cys-
Pro
Pro is an abbreviation meaning "professional".
Pro, PRO or variants thereof might also refer to:
People
* Miguel Pro (1891–1927), Mexican priest
* Pro Hart (1928–2006), Australian painter
* Mlungisi Mdluli (born 1980), South African ret ...
-
Arg-
Gly-NH
2, with the cysteine residues forming a
disulfide bond
In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups.
In inor ...
and the ''C''-terminus of the sequence converted to a
primary amide. Lysine vasopressin (lypressin) has a
lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...
in place of the arginine as the eighth amino acid, and is found in
pig
The pig (''Sus domesticus''), also called swine (: swine) or hog, is an omnivorous, domesticated, even-toed, hoofed mammal. It is named the domestic pig when distinguishing it from other members of the genus '' Sus''. Some authorities cons ...
s and some related animals, whereas arginine vasopressin is found in humans.
The structure of
oxytocin
Oxytocin is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. Present in animals since early stages of evolution, in humans it plays roles in behavior that include Human bonding, ...
is very similar to that of the vasopressins: It is also a nonapeptide with a disulfide bridge and its amino acid sequence differs at only two positions. The two genes are located on the same chromosome separated by a relatively small distance of less than 15,000 bases in most species. The
magnocellular neurons that secrete vasopressin are adjacent to magnocellular neurons that secrete oxytocin, and are similar in many respects. The similarity of the two peptides can cause some cross-reactions: oxytocin has a slight antidiuretic function, and high levels of AVP can cause uterine contractions.
Comparison of vasopressin and oxytocin neuropeptide families:
Medical use
Vasopressin is used to manage anti-diuretic hormone deficiency. Vasopressin is used to treat
diabetes insipidus
Diabetes insipidus (DI) is a condition characterized by large amounts of dilute urine and increased thirst. The amount of urine produced can be nearly 20 liters per day. Reduction of fluid has little effect on the concentration of the urine. ...
related to low levels of antidiuretic hormone. It is available as Pressyn.
Vasopressin has off-label uses and is used in the treatment of vasodilatory shock, gastrointestinal bleeding,
ventricular tachycardia
Ventricular tachycardia (V-tach or VT) is a cardiovascular disorder in which fast heart rate occurs in the ventricles of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple ...
and ventricular fibrillation.
Vasopressin agonists are used therapeutically in various conditions, and its long-acting synthetic analogue
desmopressin
Desmopressin, sold under the trade name DDAVP among others, is a medication used to treat diabetes insipidus, bedwetting, hemophilia A, von Willebrand disease, and high blood urea levels. In hemophilia A and von Willebrand disease, it should ...
is used in conditions featuring low vasopressin secretion, as well as for control of bleeding (in some forms of
von Willebrand disease
Von Willebrand disease (VWD) is the most common heredity, hereditary coagulopathy, blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of ...
and in mild
haemophilia A
Haemophilia A (or hemophilia A) is a blood clotting disorder caused by a genetic deficiency in clotting factor VIII, thereby resulting in significant susceptibility to bleeding, both internally and externally. This condition occurs almost exclu ...
) and in extreme cases of bedwetting by children.
Terlipressin
Terlipressin, sold under the brand name Terlivaz among others, is an analogue of vasopressin used as a vasoactive drug in the management of low blood pressure. It has been found to be effective when norepinephrine does not help. Terlipressin ...
and related analogues are used as
vasoconstrictor
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 vasodilation, the widening of blood vesse ...
s in certain conditions. Use of vasopressin analogues for
esophageal varices
Esophageal varices are extremely Vasodilation, dilated sub-mucosal veins in the lower third of the esophagus. They are most often a consequence of portal hypertension, commonly due to cirrhosis. People with esophageal varices have a strong tendenc ...
commenced in 1970.
Vasopressin infusions are also used as second line therapy for
septic shock
Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International C ...
patients not responding to fluid resuscitation or infusions of
catecholamine
A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine.
Cate ...
s (e.g.,
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...
or
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...
) to increase the blood pressure while sparing the use of catecholamines. These argipressins have much shorter elimination half-life (around 20 minutes) comparing to synthetic non-arginine vasopresines with much longer elimination half-life of many hours. Further, argipressins act on V1a, V1b, and V2 receptors which consequently lead to higher eGFR and lower vascular resistance in the lungs. A number of injectable arginine vasopressins are currently in clinical use in the United States and in Europe.
Pharmacokinetics
Vasopressin is administered through an
intravenous device,
intramuscular injection
Intramuscular injection, often abbreviated IM, is the medical injection, injection of a substance into a muscle. In medicine, it is one of several methods for parenteral, parenteral administration of medications. Intramuscular injection may be ...
or a
subcutaneous injection
Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion.
A subcutaneous injection is administered as a bolus (medicine), bolus into the subcutis, the layer of skin directly below the dermis and ...
. The
duration of action
Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (fo ...
depends on the mode of administration and ranges from thirty minutes to two hours. It has a
half life of ten to twenty minutes. It is widely distributed throughout the body and remains in the
extracellular fluid
In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 50–60% (range 45 to 75%) of total body weight; women and the obese typically ha ...
. It is degraded by the
liver
The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
and excreted through the
kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
s.
Arginin vasopressins for use in septic shock are intended for intravenous use only.
Side effects
The most common side effects during treatment with vasopressin are
dizziness
Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness.
Dizziness is a ...
,
angina
Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease.
Angina is typically the result of parti ...
, chest pain, abdominal cramps,
heartburn
Heartburn is a burning sensation felt behind the breastbone. It is a symptom that is commonly linked to acid reflux and is often triggered by food, particularly fatty, sugary, spicy, chocolate, citrus, onion-based and tomato-based products. Ly ...
,
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat.
Over 30 d ...
,
vomiting
Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...
, trembling,
fever
Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
,
water intoxication
Water intoxication, also known as water poisoning, hyperhydration, overhydration, or water toxemia, is a potentially fatal disturbance in brain functions that can result when the normal balance of electrolytes in the body is pushed outside safe ...
, pounding sensation in the head,
diarrhoea
Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
, sweating, paleness, and
flatulence
Flatulence is the expulsion of gas from the Gastrointestinal tract, intestines via the anus, commonly referred to as farting. "Flatus" is the medical word for gas generated in the stomach or bowels. A proportion of intestinal gas may be swal ...
. The most severe adverse reactions are
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
and
hypersensitivity
Hypersensitivity (also called hypersensitivity reaction or intolerance) is an abnormal physiological condition in which there is an undesirable and adverse immune response to an antigen. It is an abnormality in the immune system that causes Imm ...
.
Contraindications
The use of lysine vasopressin is contraindicated in the presence of hypersensitivity to beef or pork proteins, increased
BUN
A bun is a type of bread that is round and small enough that it can generally be eaten hand-held. Whether a bun is considered sweetened or unsweetened differs between countries: it is considered sweetened in the United Kingdom, a savory bread in ...
and chronic
kidney failure
Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...
. It is recommended that it be cautiously used in instances of perioperative
polyuria
Polyuria () is excessive or an abnormally large production or Frequent urination, passage of urine (greater than 2.5 L or 3 L over 24 hours in adults). Increased production and passage of urine may also be termed as diuresis. Polyuria often appe ...
, sensitivity to the drug, asthma, seizures, heart failure, a comatose state, migraine headaches, and cardiovascular disease.
Interactions
*
alcohol
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
- may lower the antidiuretic effect
*
carbamazepine
Carbamazepine, sold under the brand name Tegretol among others, is an anticonvulsant medication used in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medications and as ...
,
chloropropamide,
clofibrate,
tricyclic antidepressants
Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains ...
and
fludrocortisone
Fludrocortisone, sold under the brand name Florinef among others, is a corticosteroid used to treat congenital adrenal hyperplasia, postural hypotension, and adrenal insufficiency. In adrenal insufficiency, it is generally taken together wit ...
may raise the antidiuretic effect
*
lithium
Lithium (from , , ) is a chemical element; it has chemical symbol, symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard temperature and pressure, standard conditions, it is the least dense metal and the ...
,
demeclocycline,
heparin
Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Heparin is a blood anticoagulant that increases the activity of antithrombin. It is used in the treatment of myocardial infarction, ...
or
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...
may lower the antidiuretic effect
* vasopressor effect may be higher with the concurrent use of
ganglionic blocking medications
Deficiency
Decreased AVP release (neurogenic — i.e. due to alcohol intoxication or tumour) or decreased renal sensitivity to AVP (nephrogenic, i.e. by mutation of V2 receptor or AQP) leads to
diabetes insipidus
Diabetes insipidus (DI) is a condition characterized by large amounts of dilute urine and increased thirst. The amount of urine produced can be nearly 20 liters per day. Reduction of fluid has little effect on the concentration of the urine. ...
, a condition featuring
hypernatremia
Hypernatremia, also spelled hypernatraemia, is a high concentration of sodium in the blood. Early symptoms may include a strong feeling of thirst, weakness, nausea, and loss of appetite. Severe symptoms include confusion, muscle twitching, and ...
(increased blood
sodium
Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...
concentration),
polyuria
Polyuria () is excessive or an abnormally large production or Frequent urination, passage of urine (greater than 2.5 L or 3 L over 24 hours in adults). Increased production and passage of urine may also be termed as diuresis. Polyuria often appe ...
(excess urine production), and
polydipsia
Polydipsia is excessive thirst or excess drinking.Porth, C. M. (1990). ''Pathophysiology: Concepts of altered health states''. Philadelphia: J.B. Lippincott Company. The word derives , which is derived . Polydipsia is a nonspecific symptom in v ...
(thirst).
Excess
Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) in turn can be caused by a number of problems. Some forms of
cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
can cause SIADH, particularly
small cell lung carcinoma
Small-cell carcinoma, also known as oat cell carcinoma, is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tr ...
but also a number of other tumors. A variety of diseases affecting the brain or the lung (infections, bleeding) can be the driver behind SIADH. A number of drugs have been associated with SIADH, such as certain antidepressants (
serotonin reuptake inhibitor
A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) by blocking the drug action, action of the serotonin transporter (SERT). This in turn lea ...
s and
tricyclic antidepressant
Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains ...
s), the anticonvulsant
carbamazepine
Carbamazepine, sold under the brand name Tegretol among others, is an anticonvulsant medication used in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medications and as ...
,
oxytocin
Oxytocin is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. Present in animals since early stages of evolution, in humans it plays roles in behavior that include Human bonding, ...
(used to induce and stimulate labor), and the chemotherapy drug
vincristine
Vincristine, also known as leurocristine and sold under the brand name Oncovin among others, is a chemotherapy medication used to treat a number of types of cancer. This includes acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin lym ...
. It has also been associated with
fluoroquinolones
Quinolone antibiotics constitute a large group of broad-spectrum antibiotic, broad-spectrum bacteriocidals that share a bicyclic molecule, bicyclic core structure related to the substance 4-Quinolone, 4-quinolone. They are used in human and ve ...
(including
ciprofloxacin
Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra-abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin ...
and
moxifloxacin
Moxifloxacin is an antibiotic, used to treat bacterial infections, including pneumonia, conjunctivitis, endocarditis, tuberculosis, and sinusitis. It can be given by mouth, by injection into a vein, and as an eye drop.
Common side effec ...
).
Finally, it can occur without a clear explanation.
Hyponatremia can be treated pharmaceutically through the use of
vasopressin receptor antagonists.
History
Vasopressin was elucidated and synthesized for the first time by
Vincent du Vigneaud
Vincent du Vigneaud (May 18, 1901 – December 11, 1978) was an American biochemist. He was recipient of the 1955 Nobel Prize in Chemistry "for his work on biochemically important sulphur compounds, especially for the first synthesis of a polypep ...
.
Animal studies
Evidence for an effect of AVP on monogamy vs polygamy comes from experimental studies in several species, which indicate that the precise distribution of vasopressin and vasopressin receptors in the brain is associated with species-typical patterns of social behavior. In particular, there are consistent differences between monogamous species and polygamous species in the distribution of AVP receptors, and sometimes in the distribution of vasopressin-containing axons, even when closely related species are compared.
Human studies
Vasopressin has shown
nootropic
Nootropics ( or ) (colloquially brain supplements, smart drugs, cognitive enhancers, memory enhancers, or brain boosters) are chemical substances which purportedly improve cognitive functions, such as attention, memory, wakefulness, and self ...
effects on pain perception and cognitive function.
Vasopressin also plays a role in
autism
Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing d ...
,
major depressive disorder
Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive depression (mood), low mood, low self-esteem, and anhedonia, loss of interest or pleasure in normally ...
,
bipolar disorder
Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...
, and
schizophrenia
Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
.
See also
*
Syndrome of inappropriate antidiuretic hormone secretion
Syndrome of inappropriate antidiuretic hormone secretion (SIADH), also known as the syndrome of inappropriate antidiuresis (SIAD), is characterized by a physiologically inappropriate release of Vasopressin, antidiuretic hormone (ADH) either from ...
(SIADH)
*
Oxytocin
Oxytocin is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. Present in animals since early stages of evolution, in humans it plays roles in behavior that include Human bonding, ...
*
Vasopressin receptor
The actions of vasopressin are mediated by stimulation of tissue-specific G protein-coupled receptors (GPCRs) called vasopressin receptors that are classified into the V1 (V1A), V2, and V3 (V1B) receptor subtypes. These three subtypes differ ...
*
Vasopressin receptor antagonists
*
Copeptin
*
Anterior pituitary
The anterior pituitary (also called the adenohypophysis or pars anterior) is a major Organ (anatomy), organ of the endocrine system. The anterior pituitary is the glandular, Anatomical terms of location#Usage in human anatomy, anterior lobe that t ...
*
Hypothalamus
The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
*
Atrial natriuretic peptide
Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the ''NPPA'' gene. Natriuretic peptides (ANP, BNP, and CNP) are a family of ho ...
: When the atrium stretches, blood pressure is considered to be increased and sodium is excreted to lower blood pressure.
*
Renin-angiotensin system: When the blood flow through the juxtaglomerular apparatus decreases, blood pressure is considered low, and the adrenal cortex secretes aldosterone to increase sodium reabsorption in the collecting duct, thereby increasing blood pressure.
*
Bainbridge reflex: In response to stretching of the right atrium wall, heart rate increases, lowering venous blood pressure.
*
Baroreflex
The baroreflex or baroreceptor reflex is one of the body's homeostatic mechanisms that helps to maintain blood pressure at nearly constant levels. The baroreflex provides a rapid negative feedback loop in which an elevated blood pressure cause ...
: When the stretch receptors in the aortic arch and carotid sinus increase, the blood pressure is considered to be elevated and the heart rate decreases to lower blood pressure.
References
Further reading
*
{{Oxytocin and vasopressin receptor modulators
Neuropeptides
Posterior pituitary hormones
Neuroendocrinology
Renal physiology
Vasopressin receptor agonists
Orgasm
Antidiuretics
Nonapeptides
Stress hormones