Vasopressin

Imagine a single molecule that can keep your body hydrated, regulate your blood pressure, and even influence how you bond with others. This remarkable substance is vasopressin, a powerful hormone often called the "antidiuretic hormone" or ADH. It's a tiny peptide with a monumental role, orchestrating critical physiological processes that keep us in balance and respond to the world around us. Join us to uncover the multifaceted story of this essential molecule. Vasopressin is a key hormone synthesized in the hypothalamus that primarily regulates the body's water balance by influencing kidney function. Beyond hydration, vasopressin also plays a crucial role in maintaining blood pressure by constricting blood vessels and influences social behaviors in the brain. Its precise molecular structure, closely related to oxytocin, underpins its diverse actions and has led to important medical applications for conditions ranging from diabetes insipidus to septic shock.

Source: Wikipedia

AI Summary

Vasopressin is a key hormone synthesized in the hypothalamus that primarily regulates the body's water balance by influencing kidney function.
Beyond hydration, vasopressin also plays a crucial role in maintaining blood pressure by constricting blood vessels and influences social behaviors in the brain.
Its precise molecular structure, closely related to oxytocin, underpins its diverse actions and has led to important medical applications for conditions ranging from diabetes insipidus to septic shock.

Vasopressin: The Body's Unsung Hero

Deep within your brain, in a tiny but mighty region called the hypothalamus, a crucial hormone is constantly at work. It's known as vasopressin—also called Antidiuretic Hormone, or ADH—a name that hints at its primary, life-sustaining function. This small peptide is a master regulator, playing a vital role in processes from hydration to blood pressure control.

Vasopressin is first created in neurons in the hypothalamus as a larger 'prohormone' and then converted into its active form. From there, it travels down the nerve fibers, all the way to the posterior pituitary gland. Think of it like a message in a bottle, journeying to its release point.

When your body senses a rise in the concentration of solutes in your extracellular fluid—meaning you're becoming dehydrated—vasopressin is quickly released into your bloodstream. This triggers a cascade of effects designed to restore balance, primarily by telling your kidneys to conserve water.

Keeping the Balance: The Kidneys' Ally

Vasopressin's most famous job is regulating your body's water balance. When it reaches your kidneys, it acts like a strict supervisor, instructing them to reabsorb more solute-free water back into your circulation. This means less water is lost in your urine, making your pee more concentrated and reducing its volume.

How does it do this? Vasopressin increases the number of tiny water channels, called Aquaporin-2, on the surface of kidney cells in structures like the collecting ducts. These channels are like tiny pores that allow water to flow freely back into the bloodstream, following the natural osmotic gradient.

But it doesn't stop there. Vasopressin also boosts the reabsorption of urea and sodium in specific parts of the kidney. This intricate dance creates a higher concentration gradient within the kidney's inner medulla, which is essential for maximizing water reabsorption through those Aquaporin channels. It's a finely tuned system, critical for maintaining proper hydration.

A Silent Regulator: Blood Pressure Control

Beyond its role in hydration, vasopressin is also a potent vasoconstrictor. When released in higher concentrations, it causes the small arteries—the arterioles—to narrow. This increases the resistance to blood flow throughout your body, which in turn helps to raise arterial blood pressure. It's a backup system, kicking in when your body needs to maintain circulation.

Beyond the Body: Brain Roles

Interestingly, some vasopressin is released directly into the brain, where it plays a surprising role in social behavior. Studies, particularly in prairie voles, have shown its influence on pair-bonding and even sexual motivation. It helps coordinate the brain's reward circuits, fostering strong social connections.

Within the brain, vasopressin also acts as a kind of internal clock, released in a circadian rhythm by specific neurons, influencing sleep-wake cycles. There's even evidence suggesting it might have pain-relieving effects, which can vary based on stress levels and biological sex. It's truly a hormone with many hats!

The Molecular Blueprint

Vasopressin is a relatively small peptide, made up of just nine amino acids. Its sequence, in humans, is Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2, with a special disulfide bond between the two cysteine residues. This intricate structure gives it its unique functionality.

This hormone also has a relatively short half-life, lasting only about 16 to 24 minutes in the bloodstream. This rapid turnover allows the body to precisely and quickly adjust its levels, ensuring tight control over the processes it regulates. Another version, lysine vasopressin, functions similarly in pigs and was once used therapeutically.

Remarkably, vasopressin shares a close evolutionary kinship with another famous hormone: oxytocin. Both are nonapeptides—meaning they have nine amino acids—and their structures differ at only two positions. This structural similarity can sometimes lead to fascinating cross-reactions, where high levels of one might partially mimic the effects of the other.

Vertebrate Vasopressin Family
Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2	Argipressin (AVP, ADH)	Most mammals
Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Lys-Gly-NH2	Lypressin (LVP)	Pigs, hippos, warthogs, some marsupials
Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2	Phenypressin	Some marsupials
Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Arg-Gly-NH2	Vasotocin†	Non-mammals
Vertebrate Oxytocin Family
Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2	Oxytocin (OXT)	Most mammals, ratfish
Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Pro-Gly-NH2	Prol-Oxytocin	Some New World monkeys, northern tree shrews
Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Ile-Gly-NH2	Mesotocin	Most marsupials, all birds, reptiles, amphibians, lungfishes, coelacanths
Cys-Tyr-Ile-Gln-Ser-Cys-Pro-Ile-Gly-NH2	Seritocin	Frogs
Cys-Tyr-Ile-Ser-Asn-Cys-Pro-Ile-Gly-NH2	Isotocin	Bony fishes
Cys-Tyr-Ile-Ser-Asn-Cys-Pro-Gln-Gly-NH2	Glumitocin	Skates
Cys-Tyr-Ile-Asn/Gln-Asn-Cys-Pro-Leu/Val-Gly-NH2	Various tocins	Sharks
Invertebrate VP/OT Superfamily
Cys-Leu-Ile-Thr-Asn-Cys-Pro-Arg-Gly-NH2	Inotocin	Locust
Cys-Phe-Val-Arg-Asn-Cys-Pro-Thr-Gly-NH2	Annetocin	Earthworm
Cys-Phe-Ile-Arg-Asn-Cys-Pro-Lys-Gly-NH2	Lys-Connopressin	Geography & imperial cone snail, pond snail, sea hare, leech
Cys-Ile-Ile-Arg-Asn-Cys-Pro-Arg-Gly-NH2	Arg-Connopressin	Striped cone snail
Cys-Tyr-Phe-Arg-Asn-Cys-Pro-Ile-Gly-NH2	Cephalotocin	Octopus
Cys-Phe-Trp-Thr-Ser-Cys-Pro-Ile-Gly-NH2	Octopressin	Octopus
†Vasotocin is the evolutionary progenitor of all the vertebrate neurohypophysial hormones.

Regulation and Secretion

Vasopressin's production is meticulously controlled by your body's internal clock. The genes responsible for vasopressin are regulated by 'clock controlled genes' in a complex transcription-translation feedback loop. This ensures its levels fluctuate in sync with your circadian rhythm.

The most powerful stimulus for vasopressin secretion is an increase in plasma osmolality—meaning your blood is becoming too concentrated. However, a significant drop in blood volume, detected by arterial baroreceptors, can also trigger its release, even overriding the osmolality signals if the situation is critical. Your body prioritizes blood pressure when necessary.

While primarily released from the posterior pituitary, other neurons in the hypothalamus can release vasopressin that travels to the anterior pituitary. Here, it works with other hormones to stimulate the production of ACTH, a hormone involved in the stress response. Even the stress of surgery, particularly abdominal procedures, significantly elevates vasopressin levels.

How Vasopressin Works: The Receptors

Vasopressin exerts its effects by binding to specific receptors on cell surfaces. There are three main types, each initiating different cellular responses and found in distinct locations throughout the body, allowing vasopressin to perform its diverse roles.

Type	Second messenger system	Locations	Actions	Agonists	Antagonists
AVPR1A	Phosphatidylinositol/calcium	Liver, kidney, peripheral vasculature, brain	Vasoconstriction, glycogen breakdown, platelet aggregation, and release of factor VIII and von Willebrand factor; social recognition, circadian tau	Felypressin	
AVPR1B or AVPR3	Phosphatidylinositol/calcium	Pituitary gland, brain	Adrenocorticotropic hormone secretion in response to stress; social interpretation of olfactory cues		
AVPR2	Adenylate cyclase/cAMP	Basolateral membrane of the cells lining the collecting ducts of the kidneys (especially the cortical and outer medullary collecting ducts)	Insertion of aquaporin-2 (AQP2) channels (water channels). This allows water to be reabsorbed down an osmotic gradient, and so the urine is more concentrated. Release of von Willebrand factor and surface expression of P-selectin through exocytosis of Weibel-Palade bodies from endothelial cells	AVP, desmopressin	"-vaptan" diuretics, i.e. tolvaptan

Medical Applications

Given its vital functions, vasopressin and its synthetic analogs are valuable tools in medicine. It's directly used to manage conditions like diabetes insipidus, where the body either doesn't produce enough ADH or the kidneys don't respond to it, leading to excessive urination and thirst.

Beyond its primary role, vasopressin has crucial 'off-label' uses. It's a second-line therapy for severe vasodilatory shock, like septic shock, helping to raise dangerously low blood pressure when other medications, such as catecholamines, aren't sufficient. It also finds use in treating gastrointestinal bleeding and certain cardiac arrhythmias.

Long-acting synthetic versions, like desmopressin, are used not only for ADH deficiency but also for conditions involving bleeding disorders, such as certain types of von Willebrand disease and mild hemophilia A, by promoting the release of clotting factors. It can even help children with severe bedwetting.

When administered, vasopressin can be given intravenously, intramuscularly, or subcutaneously, with effects lasting from 30 minutes to two hours. It's rapidly processed by the liver and excreted by the kidneys, reinforcing the need for continuous monitoring in critical care settings.

When Things Go Wrong: Deficiency and Excess

If your body doesn't release enough vasopressin, or your kidneys become insensitive to it, you can develop diabetes insipidus. This leads to hypernatremia—high blood sodium—excessive urine production (polyuria), and intense thirst (polydipsia), as your body struggles to retain water.

Conversely, an excess of vasopressin can lead to the Syndrome of Inappropriate Antidiuretic Hormone secretion, or SIADH. This condition causes your body to retain too much water, diluting your blood and leading to dangerously low sodium levels (hyponatremia). SIADH can be triggered by various factors, including certain cancers, brain or lung diseases, and even some common medications like antidepressants or antibiotics.

Side Effects and Interactions

While vital, vasopressin treatment isn't without its potential downsides. Common side effects can include dizziness, chest pain, nausea, and abdominal cramps. More severe reactions, though rare, can involve myocardial infarction or hypersensitivity, so its use is carefully monitored.

Its use is also contraindicated in cases of hypersensitivity to certain animal proteins or severe kidney failure. Caution is advised for patients with asthma, seizures, heart failure, or cardiovascular disease. Furthermore, vasopressin's effects can be altered by other substances.

Alcohol: May reduce the antidiuretic effect Carbamazepine, Chloropropamide, Tricyclic Antidepressants: May enhance the antidiuretic effect Lithium, Demeclocycline, Heparin: May lower the antidiuretic effect Ganglionic Blocking Medications: May heighten vasopressor effects

A Legacy of Discovery and Ongoing Research

The groundbreaking work to elucidate and synthesize vasopressin for the first time was carried out by Vincent du Vigneaud, a monumental achievement in biochemistry that earned him a Nobel Prize. His work paved the way for understanding this complex hormone.

Research into vasopressin continues to reveal its far-reaching impact. Animal studies provide fascinating insights into its role in behaviors like monogamy, showing how the distribution of vasopressin receptors in the brain can dictate species-typical social structures. In humans, studies explore its potential in cognitive function, pain perception, and its links to conditions like autism, major depressive disorder, and bipolar disorder. It's clear that this small peptide holds many more secrets yet to be uncovered.

Article

Vasopressin

Mammalian vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travels down the axon terminating in the posterior pituitary, and is released from vesicles 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 nephrons. Second, AVP constricts arterioles, which increases peripheral vascular resistance and raises arterial blood pressure.

A third function is possible. Some AVP may be released directly into the brain from the hypothalamus, and may play an important role in social behavior, sexual motivation and pair bonding, and maternal responses to stress.

Vasopressin induces differentiation of stem cells into cardiomyocytes and promotes heart muscle homeostasis.

It has a very short half-life, between 16 and 24 minutes.

Physiology

Function

Vasopressin regulates the 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 and reduced urine volume. AVP released in high concentrations may also raise blood pressure by inducing moderate vasoconstriction.

AVP also may have a variety of neurological effects on the brain. It may influence pair-bonding in voles. The high-density distributions of vasopressin receptor AVPr1a in prairie vole 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 pigs and its synthetic version was used in human AVP deficiency, although it has been largely replaced by desmopressin.

Kidney

• Increasing the water permeability of 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 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, 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 by regulating the cell surface expression of urea transporters, which facilitates its reabsorption into the medullary interstitium as it travels down the concentration gradient created by removing water from the connecting tubule, cortical collecting duct, and outer medullary collecting duct. • Acute increase of sodium absorption across the ascending loop of Henle. This adds to the countercurrent multiplication which aids in proper water reabsorption later in the distal tubule and collecting duct.

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 and threonine 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 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 by neurons of the suprachiasmatic nucleus. • 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.

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 protein accumulates and is phosphorylated by CK1E. Per2 subsequently inhibits the transcription factors Clock and BMAL1 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 (alcohol) reduces the calcium-dependent secretion of AVP by blocking voltage-gated calcium channels in neurohypophyseal nerve terminals in rats. • Angiotensin II stimulates AVP secretion, in keeping with its general pressor and pro-volumic effects on the body. • Atrial natriuretic peptide inhibits AVP secretion, in part by inhibiting Angiotensin II-induced stimulation of AVP secretion. • Cortisol 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, (such as can occur in cirrhosis, nephrosis, and heart failure), 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 (except in cases of AVP-secreting tumours). Vasopressin is produced by magnocellular neurosecretory neurons in the paraventricular nucleus of hypothalamus (PVN) and supraoptic nucleus (SON). It then travels down the axon through the infundibulum 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, from which it travels through the hypophyseal portal system to the anterior pituitary, where it stimulates corticotropic cells 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 for evaluation of surgical techniques. Plasma vasopressin concentration is elevated by noxious stimuli, predominantly during abdominal surgery, especially at gut manipulation, traction of viscera, as well as abdominal insufflation with carbon dioxide during laparoscopic surgery.

Receptors

<table><thead><tr><th>Type</th><th>Second messenger system</th><th>Locations</th><th>Actions</th><th>Agonists</th><th>Antagonists</th></tr></thead><tbody><tr><td>AVPR1A</td><td>Phosphatidylinositol/calcium</td><td>Liver, kidney, peripheral vasculature, brain</td><td>Vasoconstriction, glycogen breakdown, platelet aggregation, and release of factor VIII and von Willebrand factor; social recognition, circadian tau</td><td>Felypressin</td><td></td></tr><tr><td>AVPR1B or AVPR3</td><td>Phosphatidylinositol/calcium</td><td>Pituitary gland, brain</td><td>Adrenocorticotropic hormone secretion in response to stress; social interpretation of olfactory cues</td><td></td><td></td></tr><tr><td>AVPR2</td><td>Adenylate cyclase/cAMP</td><td>Basolateral membrane of the cells lining the collecting ducts of the kidneys (especially the cortical and outer medullary collecting ducts)</td><td>Insertion of aquaporin-2 (AQP2) channels (water channels). This allows water to be reabsorbed down an osmotic gradient, and so the urine is more concentrated. Release of von Willebrand factor and surface expression of P-selectin through exocytosis of Weibel-Palade bodies from endothelial cells</td><td>AVP, desmopressin</td><td>"-vaptan" diuretics, i.e. tolvaptan</td></tr></tbody></table>

Structure and relation to oxytocin

Chemical structure of the arginine vasopressin (argipressin) with an arginine at the 8th amino acid position. Lysine vasopressin differs only in having a lysine in this position.

Chemical structure of oxytocin. Differs from AVP at only the 3rd and 8th position.

The vasopressins are peptides consisting of nine amino acids (nonapeptides). The amino acid sequence of arginine vasopressin (argipressin) is Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2, with the cysteine residues forming a disulfide bond and the C-terminus of the sequence converted to a primary amide. Lysine vasopressin (lypressin) has a lysine in place of the arginine as the eighth amino acid, and is found in pigs and some related animals, whereas arginine vasopressin is found in humans.

The structure of oxytocin 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:

<table><thead><tr><th>Vertebrate Vasopressin Family</th></tr></thead><tbody><tr><td>Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2</td><td>Argipressin (AVP, ADH)</td><td>Most mammals</td></tr><tr><td>Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Lys-Gly-NH2</td><td>Lypressin (LVP)</td><td>Pigs, hippos, warthogs, some marsupials</td></tr><tr><td>Cys-Phe-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2</td><td>Phenypressin</td><td>Some marsupials</td></tr><tr><td>Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Arg-Gly-NH2</td><td>Vasotocin†</td><td>Non-mammals</td></tr><tr><td>Vertebrate Oxytocin Family</td></tr><tr><td>Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2</td><td>Oxytocin (OXT)</td><td>Most mammals, ratfish</td></tr><tr><td>Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Pro-Gly-NH2</td><td>Prol-Oxytocin</td><td>Some New World monkeys, northern tree shrews</td></tr><tr><td>Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Ile-Gly-NH2</td><td>Mesotocin</td><td>Most marsupials, all birds, reptiles, amphibians, lungfishes, coelacanths</td></tr><tr><td>Cys-Tyr-Ile-Gln-Ser-Cys-Pro-Ile-Gly-NH2</td><td>Seritocin</td><td>Frogs</td></tr><tr><td>Cys-Tyr-Ile-Ser-Asn-Cys-Pro-Ile-Gly-NH2</td><td>Isotocin</td><td>Bony fishes</td></tr><tr><td>Cys-Tyr-Ile-Ser-Asn-Cys-Pro-Gln-Gly-NH2</td><td>Glumitocin</td><td>skates</td></tr><tr><td>Cys-Tyr-Ile-Asn/Gln-Asn-Cys-Pro-Leu/Val-Gly-NH2</td><td>Various tocins</td><td>Sharks</td></tr><tr><td>Invertebrate VP/OT Superfamily</td></tr><tr><td>Cys-Leu-Ile-Thr-Asn-Cys-Pro-Arg-Gly-NH2</td><td>Inotocin</td><td>Locust</td></tr><tr><td>Cys-Phe-Val-Arg-Asn-Cys-Pro-Thr-Gly-NH2</td><td>Annetocin</td><td>Earthworm</td></tr><tr><td>Cys-Phe-Ile-Arg-Asn-Cys-Pro-Lys-Gly-NH2</td><td>Lys-Connopressin</td><td>Geography & imperial cone snail, pond snail, sea hare, leech</td></tr><tr><td>Cys-Ile-Ile-Arg-Asn-Cys-Pro-Arg-Gly-NH2</td><td>Arg-Connopressin</td><td>Striped cone snail</td></tr><tr><td>Cys-Tyr-Phe-Arg-Asn-Cys-Pro-Ile-Gly-NH2</td><td>Cephalotocin</td><td>Octopus</td></tr><tr><td>Cys-Phe-Trp-Thr-Ser-Cys-Pro-Ile-Gly-NH2</td><td>Octopressin</td><td>Octopus</td></tr><tr><td>†Vasotocin is the evolutionary progenitor of all the vertebrate neurohypophysial hormones.</td></tr></tbody></table>

Medical use

Vasopressin

Vasopressin is used to manage anti-diuretic hormone deficiency. Vasopressin is used to treat diabetes insipidus 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 and ventricular fibrillation.

Vasopressin agonists are used therapeutically in various conditions, and its long-acting synthetic analogue desmopressin is used in conditions featuring low vasopressin secretion, as well as for control of bleeding (in some forms of von Willebrand disease and in mild haemophilia A) and in extreme cases of bedwetting by children. Terlipressin and related analogues are used as vasoconstrictors in certain conditions. Use of vasopressin analogues for esophageal varices commenced in 1970.

Vasopressin infusions are also used as second line therapy for septic shock patients not responding to fluid resuscitation or infusions of catecholamines (e.g., dopamine or norepinephrine) 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 or a subcutaneous injection. The duration of action 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. It is degraded by the liver and excreted through the kidneys. 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, angina, chest pain, abdominal cramps, heartburn, nausea, vomiting, trembling, fever, water intoxication, pounding sensation in the head, diarrhoea, sweating, paleness, and flatulence. The most severe adverse reactions are myocardial infarction and hypersensitivity.

Contraindications

The use of lysine vasopressin is contraindicated in the presence of hypersensitivity to beef or pork proteins, increased BUN and chronic kidney failure. It is recommended that it be cautiously used in instances of perioperative polyuria, sensitivity to the drug, asthma, seizures, heart failure, a comatose state, migraine headaches, and cardiovascular disease.

Interactions

• alcohol - may lower the antidiuretic effect • carbamazepine, chloropropamide, clofibrate, tricyclic antidepressants and fludrocortisone may raise the antidiuretic effect • lithium, demeclocycline, heparin or norepinephrine 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, a condition featuring hypernatremia (increased blood sodium concentration), polyuria (excess urine production), and polydipsia (thirst).

Excess

Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) in turn can be caused by a number of problems. Some forms of cancer can cause SIADH, particularly small cell lung carcinoma 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 inhibitors and tricyclic antidepressants), the anticonvulsant carbamazepine, oxytocin (used to induce and stimulate labor), and the chemotherapy drug vincristine. It has also been associated with fluoroquinolones (including ciprofloxacin and moxifloxacin). Finally, it can occur without a clear explanation. Hyponatremia can be treated pharmaceutically through the use of vasopressin receptor antagonists.

History

Vasopressin

Vasopressin was elucidated and synthesized for the first time by Vincent du Vigneaud.

Animal studies

Vasopressin

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

Vasopressin has shown nootropic effects on pain perception and cognitive function. Vasopressin also plays a role in autism, major depressive disorder, bipolar disorder, and schizophrenia.