A third function is possible. Some AVP may be released directly into thebrain from the hypothalamus, and may play an important role insocial behavior,sexual motivation andpair bonding, and maternal responses to stress.[10]
Vasopressin induces differentiation of stem cells intocardiomyocytes and promotes heart muscle homeostasis.[11]
It has a very short half-life, between 16 and 24 minutes.[9]
Vasopressin regulates thetonicity of body fluids. It is released from the posterior pituitary in response tohypertonicity 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 concentratedurine and reduced urine volume. AVP released in high concentrations may also raise blood pressure by inducing moderatevasoconstriction.[12]
AVP also may have a variety of neurological effects on the brain. It may influence pair-bonding involes. The high-density distributions of vasopressin receptor AVPr1a inprairie 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) orlypressin, has the same function inpigs and its synthetic version was used in human AVP deficiency, although it has been largely replaced bydesmopressin.[14]
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 theapical 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 byV2 receptors. Vasopressin also increases the concentration of calcium in the collecting duct cells, by episodic release from intracellular stores. Vasopressin, acting throughcAMP, also increases transcription of the aquaporin-2 gene, thus increasing the total number of aquaporin-2 molecules in collecting duct cells.[16]
The hormone vasopressin also stimulates the activity ofNKCC2. 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 someserine andthreonine 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 throughaquaporin 2 channels by creating a hypo-osmotic filtrate.[19][20]
Vasopressin released from posterior pituitary is associated with nausea.[22]
Recent evidence suggests that vasopressin may have analgesic effects. The analgesia effects of vasopressin were found to be dependent on both stress and sex.[23]
Vasopressin is regulated byAVP gene expression which is managed by major clock controlled genes. In this circadian circuit known as thetranscription-translation feedback loop (TTFL),Per2 protein accumulates and is phosphorylated byCK1E. Per2 subsequently inhibits the transcription factorsClock andBMAL1 in order to reduce Per2 protein levels in the cell.[24] At the same time, Per2 also inhibits the transcription factors for theAVP gene in order to regulate its expression, the expression of vasopressin, and otherAVP gene products.[25]
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.[26]
Angiotensin II stimulates AVP secretion, in keeping with its general pressor and pro-volumic effects on the body.[27]
Atrial natriuretic peptide inhibits AVP secretion, in part by inhibiting Angiotensin II-induced stimulation of AVP secretion.[27]
Cortisol inhibits secretion of antidiuretic hormone.[28]
The physiological stimulus for secretion of vasopressin is increased osmolality of the plasma, monitored by the hypothalamus. A decreased arterialblood volume, (such as can occur incirrhosis,nephrosis, andheart failure), stimulates secretion, even in the face of decreased osmolality of the plasma: it supersedes osmolality, butwith a milder effect. In other words, the unloading ofarterial baroreceptors when the arterial blood volume is low stimulates vasopressin secretion despite the presence of hypoosmolality (hyponatremia).[29]
The AVP that is measured in peripheral blood is almost all derived from secretion from theposterior pituitary gland (except in cases of AVP-secreting tumours). Vasopressin is produced bymagnocellular neurosecretory neurons in theparaventricular nucleus of hypothalamus (PVN) andsupraoptic nucleus (SON). It then travels down the axon through theinfundibulum 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 byparvocellular neurosecretory neurons of the PVN, transported and released at themedian eminence, from which it travels through thehypophyseal portal system to the anterior pituitary, where it stimulatescorticotropic cells synergistically with CRH to produce ACTH (by itself it is a weak secretagogue).[30]
Vasopressin concentration is used to measuresurgical stress for evaluation of surgical techniques. Plasma vasopressin concentration is elevated bynoxious stimuli,[31][32] predominantly during abdominal surgery,[33][34][35] especially at gut manipulation, traction of viscera,[36][37][38] as well as abdominal insufflation with carbon dioxide during laparoscopic surgery.[39][40]
Chemical structure of the arginine vasopressin (argipressin) with anarginine at the 8thamino acid position. Lysine vasopressin differs only in having alysine in this position.Chemical structure ofoxytocin. Differs from AVP at only the 3rd and 8th position.
The vasopressins arepeptides consisting of nineamino acids (nonapeptides). The amino acid sequence of arginine vasopressin (argipressin) isCys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2, with the cysteine residues forming adisulfide bond and theC-terminus of the sequence converted to aprimary amide.[48] Lysine vasopressin (lypressin) has alysine in place of the arginine as the eighth amino acid, and is found inpigs and some related animals, whereas arginine vasopressin is found in humans.[49]
The structure ofoxytocin 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. Themagnocellular 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.[50][51]
Comparison of vasopressin and oxytocin neuropeptide families:
Vasopressin is used to manage anti-diuretic hormone deficiency. Vasopressin is used to treatdiabetes insipidus related to low levels of antidiuretic hormone. It is available as Pressyn.[53]
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 analoguedesmopressin is used in conditions featuring low vasopressin secretion, as well as for control of bleeding (in some forms ofvon Willebrand disease and in mildhaemophilia A) and in extreme cases of bedwetting by children.Terlipressin and related analogues are used asvasoconstrictors in certain conditions. Use of vasopressin analogues foresophageal varices commenced in 1970.[54]
Vasopressin infusions are also used as second line therapy forseptic shock patients not responding to fluid resuscitation or infusions ofcatecholamines (e.g.,dopamine ornorepinephrine) 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, increasedBUN and chronickidney failure. It is recommended that it be cautiously used in instances of perioperativepolyuria, sensitivity to the drug, asthma, seizures, heart failure, a comatose state, migraine headaches, and cardiovascular disease.[53]
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 todiabetes insipidus, a condition featuringhypernatremia (increased bloodsodium concentration),polyuria (excess urine production), andpolydipsia (thirst).
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.[56]
Atrial natriuretic peptide: 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: 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.
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