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.[10]
Vasopressin induces differentiation of stem cells into
cardiomyocytes and promotes heart muscle homeostasis.[11]
It has a very short half-life, between 16 and 24 minutes.[9]
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.[12]
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.[13]
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.[14]
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 of collecting tubule and collecting duct epithelial cells.[15] 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.[16]
Vasopressin released from posterior pituitary is associated with nausea.[20]
Recent evidence suggests that vasopressin may have analgesic effects. The analgesia effects of vasopressin were found to be dependent on both stress and sex.[21]
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.[22] 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.[23]
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.[24]
Angiotensin II stimulates AVP secretion, in keeping with its general pressor and pro-volumic effects on the body.[25]
Atrial natriuretic peptide inhibits AVP secretion, in part by inhibiting Angiotensin II-induced stimulation of AVP secretion.[25]
Cortisol inhibits secretion of antidiuretic hormone.[26]
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, vasopressin secretion is also stimulated in the presence of hypoosmolality (hyponatremia) when the arterial blood volume is low by the unloading of
baroreceptors.[27]
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).[28]
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,[29][30] predominantly during abdominal surgery,[31][32][33] especially at gut manipulation, traction of viscera,[34][35][36] as well as abdominal insufflation with carbon dioxide during laparoscopic surgery.[37][38]
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.[46] 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.[47]
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.[48][49]
Comparison of vasopressin and oxytocin neuropeptide families:
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.[51]
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.[52]
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.
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.[51]
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).
Vasopressin was elucidated and synthesized for the first time by
Vincent du Vigneaud.
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.[54]
^Chapman IM, Professor of Medicine, Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital.
"Central Diabetes Insipidus". MSD. Merck & Co. Inc.
^Wang XM, Dayanithi G, Lemos JR, Nordmann JJ, Treistman SN (November 1991). "Calcium currents and peptide release from neurohypophysial terminals are inhibited by ethanol". The Journal of Pharmacology and Experimental Therapeutics. 259 (2): 705–11.
PMID1941619.
^
abMatsukawa T, Miyamoto T (March 2011). "Angiotensin II-stimulated secretion of arginine vasopressin is inhibited by atrial natriuretic peptide in humans". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 300 (3): R624–9.
doi:
10.1152/ajpregu.00324.2010.
PMID21123762.
^Collège des enseignants d'endocrinologie, diabète et maladie (2012-01-30). Endocrinologie, diabétologie et maladies métaboliques. Elsevier Masson.
ISBN978-2-294-72233-2.
^Garrahy A, Thompston CJ (2019). "General Principles, Diabetes, Metabolism, Obesity, Gastrointestinal Hormones, Aging, Endocrine Toxicology". Encyclopedia of Endocrine Diseases. 1 (2): 969–974.
^Day TA, Sibbald JR (June 1990). "Noxious somatic stimuli excite neurosecretory vasopressin cells via A1 cell group". The American Journal of Physiology. 258 (6 Pt 2): R1516-20.
doi:
10.1152/ajpregu.1990.258.6.R1516.
PMID2360697.
^Höglund OV, Hagman R, Olsson K, Olsson U, Lagerstedt AS (October 2014). "Intraoperative changes in blood pressure, heart rate, plasma vasopressin, and urinary noradrenalin during elective ovariohysterectomy in dogs: repeatability at removal of the 1st and 2nd ovary". Veterinary Surgery. 43 (7): 852–9.
doi:
10.1111/j.1532-950X.2014.12264.x.
PMID25130060.
^Goldmann A, Hoehne C, Fritz GA, Unger J, Ahlers O, Nachtigall I, et al. (September 2008). "Combined vs. Isoflurane/Fentanyl anesthesia for major abdominal surgery: Effects on hormones and hemodynamics". Medical Science Monitor. 14 (9): CR445-52.
PMID18758414.
^Joo KW, Jeon US, Kim GH, Park J, Oh YK, Kim YS, et al. (October 2004). "Antidiuretic action of oxytocin is associated with increased urinary excretion of aquaporin-2". Nephrology, Dialysis, Transplantation. 19 (10): 2480–6.
doi:
10.1093/ndt/gfh413.
PMID15280526.
^Acher R, Chauvet J (July 1995). "The neurohypophysial endocrine regulatory cascade: precursors, mediators, receptors, and effectors". Frontiers in Neuroendocrinology. 16 (3): 237–89.
doi:
10.1006/frne.1995.1009.
PMID7556852.
S2CID12739464.
^Baum S, Nusbaum M (March 1971). "The control of gastrointestinal hemorrhage by selective mesenteric arterial infusion of vasopressin". Radiology. 98 (3): 497–505.
doi:
10.1148/98.3.497.
PMID5101576.
^
abVerbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH (November 2007). "Hyponatremia treatment guidelines 2007: expert panel recommendations". The American Journal of Medicine. 120 (11 Suppl 1): S1–21.
CiteSeerX10.1.1.499.7585.
doi:
10.1016/j.amjmed.2007.09.001.
PMID17981159.
^Iovino M, Messana T, De Pergola G, Iovino E, Dicuonzo F, Guastamacchia E, et al. (2018). "The Role of Neurohypophyseal Hormones Vasopressin and Oxytocin in Neuropsychiatric Disorders". Endocrine, Metabolic & Immune Disorders Drug Targets. 18 (4): 341–347.
doi:
10.2174/1871530318666180220104900.
PMID29468985.
S2CID3465601.