Vasopressin: Difference between revisions
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'''Arginine vasopressin''' ('''AVP'''), also known as '''antidiuretic hormone''' ('''ADH''') or '''argipressin''', is a | '''Arginine vasopressin''' ('''AVP'''), also known as '''vasopressin''', '''antidiuretic hormone''' ('''ADH''') or '''argipressin''', is a mammalian [[hormone]] that is mainly released when the body is low on [[water]]; it causes the [[kidney]]s to conserve water by concentrating the [[urine]] and reducing urine volume. It also causes vasoconstriction.<ref>{{MeSH|Vasopressins}}</ref> | ||
A very similar substance, '''lysine vasopressin''' ('''LVP''') or '''lypressin''', has the same function in [[pig]]s and is often used in human therapy. | A very similar substance, '''lysine vasopressin''' ('''LVP''') or '''lypressin''', has the same function in [[pig]]s and is often used in human therapy. | ||
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Many factors influence the secretion of vasopressin: | Many factors influence the secretion of vasopressin: | ||
* [[Ethanol]] and [[caffeine]] ''reduce'' vasopressin secretion. The resulting decrease in water reabsorption by the kidneys leads to a higher [[urine]] output. [[Coffee]] is an example of a food product that suppresses the body's release of antidiuretic hormones, due to its level of caffeine. This intake of caffeine causes the body to lose more water and may lead to [[dehydration]] if consumed excessively. | * [[Ethanol]] and [[caffeine]] ''reduce'' vasopressin secretion. The resulting decrease in water reabsorption by the kidneys leads to a higher [[urine]] output. [[Coffee]] is an example of a food product that suppresses the body's release of antidiuretic hormones, due to its level of caffeine. This intake of caffeine causes the body to lose more water and may lead to [[dehydration]] if consumed excessively. | ||
* [[Angiotensin]] II ''stimulates'' the secretion of vasopressin.<ref>Vander | * [[Angiotensin]] II ''stimulates'' the secretion of vasopressin.<ref>Vander AJ ''Renal Physiology'' McGraw-Hill, 1991</ref> | ||
===Sources=== | ===Sources=== | ||
| Line 102: | Line 57: | ||
In several species, that the distribution of vasopressin and vasopressin receptors in the brain is associated with species-typical patterns of social behavior. In particular, there are differences between monogamous species and promiscuous species in the distribution of vasopressin receptors, and sometimes in the distribution of vasopressin-containing axons, even when closely-related species are compared. Moreover, studies involving either injecting vasopressin agonists into the brain, or blocking the actions of vasopressin, support the hypothesis that vasopressin is involved in aggression towards other males. There is also evidence that differences in the vasopressin receptor gene between individual members of a species might be predictive of differences in social behavior. | In several species, that the distribution of vasopressin and vasopressin receptors in the brain is associated with species-typical patterns of social behavior. In particular, there are differences between monogamous species and promiscuous species in the distribution of vasopressin receptors, and sometimes in the distribution of vasopressin-containing axons, even when closely-related species are compared. Moreover, studies involving either injecting vasopressin agonists into the brain, or blocking the actions of vasopressin, support the hypothesis that vasopressin is involved in aggression towards other males. There is also evidence that differences in the vasopressin receptor gene between individual members of a species might be predictive of differences in social behavior. | ||
===Summary Table=== | ===Summary Table=== | ||
{{main|vasopressin receptor}} | |||
This table summarizes some of the actions of AVP at its three [[cell surface receptor]]s which are differently expressed in different tissues and exerting different actions. | |||
{| class="wikitable" | {| class="wikitable" | ||
| | |+ Summary of vasopressin receptors | ||
! Type!! [[Second messenger system]]!! Locations!! Actions | |||
|- | |- | ||
| [[Arginine vasopressin receptor 1A|AVPR1A]] || [[phosphatidylinositol]]/[[calcium]] || [[liver]], [[kidney]], peripheral vasculature, [[brain || [[vasoconstriction]], [[gluconeogenesis]], [[platelet]] aggregation, and release of [[factor VIII]] and [[von Willebrand factor]]; social recognition<ref>Bielsky IF | | [[Arginine vasopressin receptor 1A|AVPR1A]] || [[phosphatidylinositol]]/[[calcium]] || [[liver]], [[kidney]], peripheral vasculature, [[brain]] || [[vasoconstriction]], [[gluconeogenesis]], [[platelet]] aggregation, and release of [[factor VIII]] and [[von Willebrand factor]]; social recognition<ref>Bielsky IF ''et al.'' (2004) Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice ''Neuropsychopharmacology'' 29:483-93 PMID 14647484</ref>, circadian tau<ref>Wersinger SR ''et al.'' (2007) Vasopressin 1a receptor knockout mice have a subtle olfactory deficit but normal aggression ''Genes Brain Behav''PMID 17083331</ref> | ||
|- | |- | ||
| [[Arginine vasopressin receptor 1B|AVPR1B]] || [[phosphatidylinositol]]/[[calcium]] || [[pituitary gland]], [[brain]] || [[adrenocorticotropic hormone]] secretion in response to stress<ref>Lolait SJ | | [[Arginine vasopressin receptor 1B|AVPR1B]] || [[phosphatidylinositol]]/[[calcium]] || [[pituitary gland]], [[brain]] || [[adrenocorticotropic hormone]] secretion in response to stress<ref>Lolait SJ ''et al.'' (2007) The hypothalamic-pituitary-adrenal axis response to stress in mice lacking functional vasopressin V1b receptors ''Endocrinology'' 148:849-56 PMID 17122081</ref>; social interpretation to olfactory cues<ref>Wersinger SR''et al.'' (2004) Social motivation is reduced in vasopressin 1b receptor null mice despite normal performance in an olfactory discrimination task ''Horm Behav'' 46:638-45 PMID 15555506</ref> | ||
|- | |- | ||
| [[Arginine vasopressin receptor 2|AVPR2]] || [[adenylate cyclase]]/[[cAMP]] || apical membrane of the cells lining the [[collecting duct]]s 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. | | [[Arginine vasopressin receptor 2|AVPR2]] || [[adenylate cyclase]]/[[cAMP]] || apical membrane of the cells lining the [[collecting duct]]s 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. | ||
|} | |} | ||
==Structure and relation to oxytocin== | ==Structure and relation to oxytocin== | ||
| Line 174: | Line 131: | ||
==Pharmacology== | ==Pharmacology== | ||
===Vasopressin analogues=== | ===Vasopressin analogues=== | ||
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 extreme cases of bedwetting by children. | |||
[[Hepatorenal syndrome]] maybe be treated with [[terlipressin]] and related analogues which are splanchnic [[vasocontrictor]]s .<ref>Sanyal AJ ''et al.'' (2008) A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome ''Gastroenterology'' 134:1360-8 PMID 18471513</ref><ref>Martín-Llahí M ''et al.'' (2008) Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study ''Gastroenterology'' 134:1352-9 PMID 18471512</ref> | |||
[[Esophageal varices]] may be treated with vasopressin analogues.<ref>Baum S ''et al.'' (1970) The control of gastrointestinal hemorrhage by selective mesenteric infusion of pitressin ''Gastroenterology'' 58:926</ref> | |||
PMID 14711909.</ref> | |||
In [[septic shock]], vasopressin infusion has been used as a second line of management in patients not responding to high dose of inotropes (e.g., [[dopamine]] or [[epinephrine]]). | |||
In [[asystole|asystolic]] [[cardiac arrest]], vasopressin may be more effective than epinephrine according to a randomized controlled trial<ref>Wenzel V ''et al.'' (2004) European Resuscitation Council Vasopressor during Cardiopulmonary Resuscitation Study Group. A comparison of AVP and epinephrine for out-of-hospital cardiopulmonary resuscitation ''N Engl J Med'' 350:105-13 PMID 14711909.</ref> and a [[cohort study]]. <ref>Grmec S, Mally S (2006) Vasopressin improves outcome in out-of-hospital cardiopulmonary resuscitation of ventricular fibrillation and pulseless ventricular tachycardia: an observational cohort study ''Crit Care'' 10:R13 PMID 16420660</ref> Vasopressin may be combined with a [[corticosteroid]].<ref>{{Cite journal | |||
| doi = 10.1001/archinternmed.2008.509 | |||
| volume = 169 | |||
| pages = 15-24 | |||
| last = Mentzelopoulos | |||
| first = SD | |||
| coauthors = ''et al.'' | title = Vasopressin, Epinephrine, and Corticosteroids for In-Hospital Cardiac Arrest | |||
| journal = Arch Intern Med | |||
| accessdate = 2009-01-13 | |||
| date = 2009-01-12 | |||
}}</ref> | |||
===Vasopressin receptor inhibition=== | ===Vasopressin receptor inhibition=== | ||
In hyponatremia, [[demeclocycline]], a tetracycline antibiotic, is sometimes used to block the action of vasopressin in the kidney when there is inappropriately high secretion of vasopressin (SIADH, see above) and fluid restriction has not corrected the hyponatremia. | In [[hyponatremia]], [[demeclocycline]], a tetracycline antibiotic, is sometimes used to block the action of vasopressin in the kidney when there is inappropriately high secretion of vasopressin (SIADH, see above) and fluid restriction has not corrected the hyponatremia. | ||
In [[heart failure]], tolvaptan, a vasopressin antagonist, may be beneficial according to a [[randomized controlled trial]].<ref>Gheorghiade M et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials | In [[heart failure]], tolvaptan, a vasopressin antagonist, may be beneficial according to a [[randomized controlled trial]].<ref>Gheorghiade M ''et al.'' (2007) Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials ''JAMA'' 297:1332-43 PMID 17384438</ref><ref>Konstam MA ''et al.'' (2007) Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. ''JAMA'' 297:1319-31 PMID 17384437</ref> Tolvaptan is a selective [[cell surface receptor]]s V2 antagonist in the distal nephron which causes loss of free water.<ref>Goldsmith SR, Gheorghiade M (2005) Vasopressin antagonism in heart failure ''J Am Coll Cardiol'' 46:1785-91 PMID 16286160</ref> Other [[vasopressin]] antagonists ([[conivaptan]], [[tolvaptan]], [[relcovaptan]], [[lixivaptan]]) act mainly on V1a [[cell surface receptor]]s. | ||
[[Tolvaptan]] can be used for [[hyponatremia]].<ref>(2009) [http://www.medicalletter.org/restricted/articles/w1326c.html Tolvaptan (Samsca) for Hyponatremia] The Medical Letter</ref> | |||
==References== | ==References== | ||
<div class="references-small"><references /></div> | <div class="references-small"><references /></div> | ||
[[Category:Suggestion Bot Tag]] | |||
Latest revision as of 12:01, 4 November 2024
Arginine vasopressin (antidiuretic hormone) -human
| |
| Identifiers | |
| Symbol(s) | AVP VP, ADH |
| Entrez | 551 |
| OMIM | 192340 |
| RefSeq | NM_000490 |
| UniProt | P01185 |
| Other data | |
| Locus | Chr. 20 p13 |
Arginine vasopressin (AVP), also known as vasopressin, antidiuretic hormone (ADH) or argipressin, is a mammalian hormone that is mainly released when the body is low on water; it causes the kidneys to conserve water by concentrating the urine and reducing urine volume. It also causes vasoconstriction.[1]
A very similar substance, lysine vasopressin (LVP) or lypressin, has the same function in pigs and is often used in human therapy.
Vasopressin is a peptide hormone liberated from a preprohormone precursor, the bulk of which is synthesized by the magnocellular neurons of the paraventricular and supraoptic nuclei of the hypothalamus, and transported to the posterior part of the pituitary gland from where it is secreted into the blood stream. Some of it is also released directly into the brain from the dendrites of the magnocellular neurons as well as from other brain neurons (see below).
Physiology
Control
Vasopressin is secreted from the posterior pituitary gland in response to reductions in plasma volume and in response to increases in the plasma osmolality:
- Secretion in response to reduced plasma volume is activated by pressure receptors in the veins, atria, and carotids.
- Secretion in response to increases in plasma osmotic pressure is mediated by osmoreceptors in the hypothalamus.
The neurons that make vasopressin, in the supraoptic nucleus and paraventricular nucleus, are themselves osmoreceptors, but they also receive synaptic input from other osmoreceptors located in regions adjacent to the anterior wall of the third ventricle. These regions include the organum vasculosum of the lamina terminalis and the subfornical organ.
Many factors influence the secretion of vasopressin:
- Ethanol and caffeine reduce vasopressin secretion. The resulting decrease in water reabsorption by the kidneys leads to a higher urine output. Coffee is an example of a food product that suppresses the body's release of antidiuretic hormones, due to its level of caffeine. This intake of caffeine causes the body to lose more water and may lead to dehydration if consumed excessively.
- Angiotensin II stimulates the secretion of vasopressin.[2]
Sources
The vasopressin that is measured in peripheral blood is almost all derived from secretion from the posterior pituitary gland (except in cases of vasopressin-secreting tumours). However there are two other sources of vasopressin with important local effects:
- Vasopressin is secreted from parvocellular neurons of the paraventricular nucleus at the median eminence into the short portal vessels of the pituitary stalk. These vessels carry the peptide to the anterior pituitary gland, where it is an important releasing factor for ACTH, acting in conjunction with CRH.
- Vasopressin is also released into the brain by several different populations of neurons (see below).
Central actions
Vasopressin released within the brain has many actions:
- It has been implicated in memory formation, including delayed reflexes, image, short- and long-term memory, though the mechanism remains unknown, and these findings are controversial. However, the synthetic vasopressin analogue desmopressin has come to interest as a likely nootropic.
- Vasopressin is released into the brain in a circadian rhythm by neurons of the suprachiasmatic nucleus of the hypothalamus.
- Vasopressin released from centrally-projecting hypothalamic neurons is involved in aggression, blood pressure regulation and temperature regulation.
In recent years there has been particular interest in the role of vasopressin in social behavior. It is thought that vasopressin, released into the brain during sexual activity, initiates and sustains patterns of activity that support the pair-bond between the sexual partners; in particular, vasopressin seems to induce the male to become aggressive towards other males.
In several species, that the distribution of vasopressin and vasopressin receptors in the brain is associated with species-typical patterns of social behavior. In particular, there are differences between monogamous species and promiscuous species in the distribution of vasopressin receptors, and sometimes in the distribution of vasopressin-containing axons, even when closely-related species are compared. Moreover, studies involving either injecting vasopressin agonists into the brain, or blocking the actions of vasopressin, support the hypothesis that vasopressin is involved in aggression towards other males. There is also evidence that differences in the vasopressin receptor gene between individual members of a species might be predictive of differences in social behavior.
Summary Table
This table summarizes some of the actions of AVP at its three cell surface receptors which are differently expressed in different tissues and exerting different actions.
| Type | Second messenger system | Locations | Actions |
|---|---|---|---|
| AVPR1A | phosphatidylinositol/calcium | liver, kidney, peripheral vasculature, brain | vasoconstriction, gluconeogenesis, platelet aggregation, and release of factor VIII and von Willebrand factor; social recognition[3], circadian tau[4] |
| AVPR1B | phosphatidylinositol/calcium | pituitary gland, brain | adrenocorticotropic hormone secretion in response to stress[5]; social interpretation to olfactory cues[6] |
| AVPR2 | adenylate cyclase/cAMP | apical 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. |
Structure and relation to oxytocin
The vasopressins are peptides consisting of nine amino acids (nonapeptides). (NB: the value in the table above of 164 amino acids is that obtained before the hormone is activated by cleavage). The amino acid sequence of AVP is Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly, with the cysteine residues form a sulfur bridge. Lysine vasopressin has a lysine in place of the arginine.
The structure of oxytocin is very similar to that of the vasopressins: it is also a nonapeptide with a sulfur bridge and its amino acid sequence differs at only two positions (see table below). These two neuropeptides are encoded by genes that arose through duplication approximately 400 million years ago. The two genes are located on the same chromosome separated by a relatively small distance of less than 15,000 bases in various species. The magnocellular neurons that make AVP are adjacent to magnocellular neurons that make 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.
Here is a table showing the superfamily of vasopressin and oxytocin neuropeptides:
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-Phe-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-Ile-Gly-NH2 Mesotocin Most marsupials, all birds, reptiles, amphibians, lungfishes Cys-Tyr-Ile-Ser-Asn-Cys-Pro-Ile-Gly-NH2 Isotocin Bony fishes 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 Diuretic Hormone 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. Only vasotocin found in hagfish & lampreys (Agnatha appeared 500 million years ago)
Role in disease
Decreased AVP release or decreased renal sensitivity to AVP leads to diabetes insipidus, a condition featuring hypernatremia (increased blood sodium content), polyuria (excess urine production), and polydipsia (thirst).
High levels of AVP secretion (syndrome of inappropriate antidiuretic hormone, SIADH) and resultant hyponatremia (low blood sodium levels) occurs in brain diseases and conditions of the lungs. In the perioperative period, the effects of surgical stress and some commonly used medications (e.g., opiates, syntocinon, anti-emetics) lead to a similar state of excess AVP secretion. This may cause mild hyponatraemia for several days.
Pharmacology
Vasopressin analogues
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 extreme cases of bedwetting by children.
Hepatorenal syndrome maybe be treated with terlipressin and related analogues which are splanchnic vasocontrictors .[7][8]
Esophageal varices may be treated with vasopressin analogues.[9]
In septic shock, vasopressin infusion has been used as a second line of management in patients not responding to high dose of inotropes (e.g., dopamine or epinephrine).
In asystolic cardiac arrest, vasopressin may be more effective than epinephrine according to a randomized controlled trial[10] and a cohort study. [11] Vasopressin may be combined with a corticosteroid.[12]
Vasopressin receptor inhibition
In hyponatremia, demeclocycline, a tetracycline antibiotic, is sometimes used to block the action of vasopressin in the kidney when there is inappropriately high secretion of vasopressin (SIADH, see above) and fluid restriction has not corrected the hyponatremia.
In heart failure, tolvaptan, a vasopressin antagonist, may be beneficial according to a randomized controlled trial.[13][14] Tolvaptan is a selective cell surface receptors V2 antagonist in the distal nephron which causes loss of free water.[15] Other vasopressin antagonists (conivaptan, tolvaptan, relcovaptan, lixivaptan) act mainly on V1a cell surface receptors.
Tolvaptan can be used for hyponatremia.[16]
References
- ↑ Anonymous (2024), Vasopressins (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Vander AJ Renal Physiology McGraw-Hill, 1991
- ↑ Bielsky IF et al. (2004) Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice Neuropsychopharmacology 29:483-93 PMID 14647484
- ↑ Wersinger SR et al. (2007) Vasopressin 1a receptor knockout mice have a subtle olfactory deficit but normal aggression Genes Brain BehavPMID 17083331
- ↑ Lolait SJ et al. (2007) The hypothalamic-pituitary-adrenal axis response to stress in mice lacking functional vasopressin V1b receptors Endocrinology 148:849-56 PMID 17122081
- ↑ Wersinger SRet al. (2004) Social motivation is reduced in vasopressin 1b receptor null mice despite normal performance in an olfactory discrimination task Horm Behav 46:638-45 PMID 15555506
- ↑ Sanyal AJ et al. (2008) A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome Gastroenterology 134:1360-8 PMID 18471513
- ↑ Martín-Llahí M et al. (2008) Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study Gastroenterology 134:1352-9 PMID 18471512
- ↑ Baum S et al. (1970) The control of gastrointestinal hemorrhage by selective mesenteric infusion of pitressin Gastroenterology 58:926
- ↑ Wenzel V et al. (2004) European Resuscitation Council Vasopressor during Cardiopulmonary Resuscitation Study Group. A comparison of AVP and epinephrine for out-of-hospital cardiopulmonary resuscitation N Engl J Med 350:105-13 PMID 14711909.
- ↑ Grmec S, Mally S (2006) Vasopressin improves outcome in out-of-hospital cardiopulmonary resuscitation of ventricular fibrillation and pulseless ventricular tachycardia: an observational cohort study Crit Care 10:R13 PMID 16420660
- ↑ Mentzelopoulos, SD; et al. (2009-01-12). "Vasopressin, Epinephrine, and Corticosteroids for In-Hospital Cardiac Arrest". Arch Intern Med 169: 15-24. DOI:10.1001/archinternmed.2008.509. Retrieved on 2009-01-13. Research Blogging.
- ↑ Gheorghiade M et al. (2007) Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials JAMA 297:1332-43 PMID 17384438
- ↑ Konstam MA et al. (2007) Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA 297:1319-31 PMID 17384437
- ↑ Goldsmith SR, Gheorghiade M (2005) Vasopressin antagonism in heart failure J Am Coll Cardiol 46:1785-91 PMID 16286160
- ↑ (2009) Tolvaptan (Samsca) for Hyponatremia The Medical Letter