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Arginine Vasopressin (AVP)

Evidence: B/C — Meaningful Human Evidence

Renal / Fluid-Balance Signaling

2 min read

Key facts

  • Research areaRenal / Fluid-Balance Signaling
  • Study records43 human

Evidence Snapshot

Evidence: B/C — Meaningful Human Evidence

What this grade covers

B applies to direct human pharmacologic/hemodynamic evidence for exact-sequence AVP: a large, real multicenter RCT (VASST, PMID 18305265, N=778) directly comparing AVP infusion to norepinephrine in septic shock, a smaller RCT in advanced vasodilatory shock (PMID 12732600, N=48), a controlled human chronic-infusion osmoregulation/fluid-balance physiology study (PMID 8222513), and an FDA-approved exact-sequence synthetic AVP product (Vasostrict) with its own labeled indication, dosing, and safety data for vasodilatory shock. C applies specifically to any generalized therapeutic-superiority or mortality-benefit claim: VASST's own primary 28-day mortality endpoint was statistically null, and the positive 90-day 'less severe shock' subgroup finding is hypothesis-generating, not confirmatory. This grade does not extend to Copeptin diagnostic evidence (a distinct Batch 16 Current subject) and does not extend AVP's grade to Desmopressin, Terlipressin, or Lypressin, all of which are separately graded analogue-programme subjects.

Regulatory Context

Native AVP is an endogenous hormone, not itself an FDA-approved drug. A synthetic, exact-sequence AVP product (Vasostrict, vasopressin injection) is FDA-approved specifically for vasodilatory shock refractory to fluids/catecholamines; this is a product-specific approval and does not mean every AVP-labeled or compounded preparation is FDA approved.

Research Takeaway

Arginine Vasopressin (AVP) is the mature 9-amino-acid neurohypophyseal hormone, distinct from its prepro-AVP precursor, neurophysin II, and Copeptin, all three of which are co-secreted cleavage products of the same precursor rather than AVP itself.

Evidence boundary: Co-secretion and shared ancestry do not make precursor fragments interchangeable with mature AVP for identity or efficacy purposes.

See all 7 evidence claims →

Quick Summary

Renal / Fluid-Balance Signaling

Arginine Vasopressin (AVP) is the body's principal antidiuretic/osmoregulatory hormone and, as the synthetic exact-sequence product Vasostrict, an FDA-approved vasopressor for refractory vasodilatory shock. Direct human evidence includes a large randomized trial (VASST) and controlled physiology studies, but VASST's own primary mortality endpoint was negative — AVP raises blood pressure in this setting without proven survival benefit over standard care.

Mechanism & Research Overview

Arginine Vasopressin (AVP) is the body's principal antidiuretic/osmoregulatory hormone and, as the synthetic exact-sequence product Vasostrict, an FDA-approved vasopressor for refractory vasodilatory shock. Direct human evidence includes a large randomized trial (VASST) and controlled physiology studies, but VASST's own primary mortality endpoint was negative — AVP raises blood pressure in this setting without proven survival benefit over standard care.

Mechanism pathway

Relationship-support labels describe the type and directness of the research available, not proof of safety or effectiveness. Indirectly supported, inferred and uncertain relationships are not equivalent to directly supported ones.

V1A receptor (vascular)

  1. CompoundArginine Vasopressin (AVP)
  2. Directly supported (Directly supported relationship)
    Biological targetV1A receptor (vascular)Receptor
  3. Directly supported (Directly supported relationship)
    Signal / mechanism stepV1A receptor activationAVP directly activates AVPR1A on vascular smooth muscle, demonstrated by hemodynamic/pressor effect in randomized human trials and the Vasostrict FDA-approved indication.
  4. Supported indirectly (Indirectly supported relationship)
    Signal / mechanism stepGq/11 -> PLC -> IP3/DAG -> intracellular Ca2+Textbook downstream Gq/11-coupled cascade for V1A engagement; not itself the focus of the cited hemodynamic-outcome trials.
  5. Leads to
    PathwayNot yet assigned
  6. Contributes to
    • Biological processSystemic vascular resistance / blood pressure increase (V1A-mediated vasoconstriction)

Relationship support in this pathway

  • Directly supported
  • Supported indirectly

Thin grey links (“Leads to”, “Contributes to”) show structure only and carry no support rating.

Relationship details

  1. Arginine Vasopressin (AVP) → V1A receptor (vascular) — Directly supportedExact-sequence AVP directly activates the V1A (AVPR1A) receptor on vascular smooth muscle, producing measurable vasoconstriction and blood-pressure increase in randomized human trials of vasodilatory/septic shock.
  2. V1A receptor activation — Directly supportedSources: avp-vasst-2008-pmid18305265, avp-dunser-2003-pmid12732600
  3. Gq/11 -> PLC -> IP3/DAG -> intracellular Ca2+ — Supported indirectly
  4. Systemic vascular resistance / blood pressure increase (V1A-mediated vasoconstriction) — contributes to the pathway (structural link, no support rating)Sources: avp-dunser-2003-pmid12732600

A specific pathway family has not yet been assigned for this relationship.

A biological process is not the same as a proven health or treatment outcome.

Relevant tissue/system context: Vascular smooth muscle (systemic vasculature)

V2 receptor (renal)

  1. CompoundArginine Vasopressin (AVP)
  2. Directly supported (Directly supported relationship)
    Biological targetV2 receptor (renal)Receptor
  3. Directly supported (Directly supported relationship)
    Signal / mechanism stepV2 receptor activationChronic low-dose AVP infusion measurably alters renal water handling in healthy human volunteers, consistent with direct V2 engagement.
  4. Supported indirectly (Indirectly supported relationship)
    Signal / mechanism stepGs -> adenylyl cyclase -> cAMP -> PKA -> AQP2 traffickingTextbook downstream Gs-coupled cascade for V2 engagement, driving aquaporin-2 trafficking in the renal collecting duct.
  5. Leads to
    PathwayNot yet assigned
  6. Contributes to
    • Biological processRenal free-water reabsorption (antidiuresis)

Relationship support in this pathway

  • Directly supported
  • Supported indirectly

Thin grey links (“Leads to”, “Contributes to”) show structure only and carry no support rating.

Relationship details

  1. Arginine Vasopressin (AVP) → V2 receptor (renal) — Directly supportedExact-sequence AVP directly activates the V2 (AVPR2) receptor in the renal collecting duct, driving antidiuretic water reabsorption, demonstrated by chronic low-dose AVP infusion altering renal water handling in healthy human volunteers.
  2. V2 receptor activation — Directly supportedSources: avp-sutters-1993-pmid8222513
  3. Gs -> adenylyl cyclase -> cAMP -> PKA -> AQP2 trafficking — Supported indirectly
  4. Renal free-water reabsorption (antidiuresis) — contributes to the pathway (structural link, no support rating)Sources: avp-sutters-1993-pmid8222513

A specific pathway family has not yet been assigned for this relationship.

A biological process is not the same as a proven health or treatment outcome.

Relevant tissue/system context: Renal collecting duct

Open in the Mechanism & Pathway Explorer→

Evidence Claims

Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.

identity

Supported

Arginine Vasopressin (AVP) is the mature 9-amino-acid neurohypophyseal hormone, distinct from its prepro-AVP precursor, neurophysin II, and Copeptin, all three of which are co-secreted cleavage products of the same precursor rather than AVP itself.

Does not establish

Evidence boundary: Co-secretion and shared ancestry do not make precursor fragments interchangeable with mature AVP for identity or efficacy purposes.

human_evidence

Supported

Exact-sequence AVP, infused intravenously, raises blood pressure and produces measurable hemodynamic effects in catecholamine-refractory vasodilatory/septic shock, evaluated in randomized controlled human trials.

Sources: Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock; Arginine Vasopressin in Advanced Vasodilatory Shock: A Prospective, Randomized, Controlled Study

Efficacy

Supported

VASST did not show a statistically significant reduction in 28-day mortality for AVP versus norepinephrine in septic shock; a subgroup signal in less-severe shock was not the trial's primary, confirmed result.

Does not establish

Evidence boundary: A single subgroup finding must not be presented as an established mortality benefit.

Sources: Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock

human_evidence

Supported

Exogenous low-dose AVP infusion measurably alters renal water handling and blunts the renin response to sodium restriction in healthy human volunteers, consistent with AVP's endogenous antidiuretic/osmoregulatory role.

Sources: Effect of chronic low-dose arginine vasopressin infusion on body fluid homoeostasis during adaptation from a high- to a low-sodium diet in normal man

Regulatory Status

Supported

Vasostrict (vasopressin injection) is an FDA-approved, synthetic, exact-sequence AVP product indicated to increase blood pressure in adults with vasodilatory shock; this approval is product-specific and does not constitute approval of AVP for any other use.

Sources: FDA Label / DailyMed Record for Vasostrict (Vasopressin Injection)

Safety

Supported

Administered AVP carries dose-related ischemic and cardiac risk (coronary/mesenteric/skin/digital ischemia, decreased cardiac output, bradycardia, tachyarrhythmia, hyponatremia), per its own FDA label and its clinical-trial adverse-event profile.

Sources: FDA Label / DailyMed Record for Vasostrict (Vasopressin Injection); Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock

Evidence Boundary

Supported

No controlled AVP evidence in this manifest establishes AVP as superior to standard vasopressors for mortality outcomes in unselected septic/vasodilatory shock; VASST's primary endpoint was negative.

Sources: Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock

Safety & Evidence Limitations

Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.

  • Higher-Priority Safety Consideration

    Coronary, mesenteric, skin, and digital ischemia; decreased cardiac output; bradycardia; tachyarrhythmia — all documented in Vasostrict's label and consistent with VASST/PMID 12732600 trial safety reporting.

  • Safety Consideration

    Reported adverse effect in AVP clinical trial and label safety data; distinct mechanism from — but analogous in category to — Desmopressin's larger, better-characterized hyponatremia signal (see Desmopressin page; not a cross-subject grade transfer).

  • Safety Consideration

    The largest AVP-vs-norepinephrine RCT did not show a mortality benefit; positive subgroup findings are hypothesis-generating only.

  • Safety Consideration

    Vasostrict's approval is scoped to vasodilatory shock refractory to fluids/catecholamines, not a general blood-pressure agent.

Research Areas Being Studied

Research areas discussed on this page reflect the Renal / Fluid-Balance Signaling category and the sources cited below.

Findings Reported in Studies

Educational summary only — reported in cited studies, not a claim of proven benefit.

Show findings from 3 human studies
  • Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock (2008):
  • Arginine Vasopressin in Advanced Vasodilatory Shock: A Prospective, Randomized, Controlled Study (2003):
  • Effect of chronic low-dose arginine vasopressin infusion on body fluid homoeostasis during adaptation from a high- to a low-sodium diet in normal man (1993):

Study Tables by Evidence Type

4 study records

Human Studies & Clinical Data(3)

Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock

2008

PMID 18305265

Population / Model
778 adults with septic shock (multicenter, double-blind RCT — VASST)
Dose / Duration / Finding

Low-dose arginine vasopressin (0.01-0.03 U/min) added to open-label vasopressors was not statistically superior to norepinephrine (5-15 mcg/min) for the primary 28-day mortality endpoint (35.4% AVP vs. 39.3% norepinephrine; RR 0.90, 95% CI 0.75-1.08, P=0.26).

Safety note

A prespecified 'less severe septic shock' subgroup showed lower 90-day mortality with AVP (35.8% vs 46.1%, P=0.04) — a hypothesis-generating subgroup signal, not the trial's primary, confirmed result.

PubMed

Arginine Vasopressin in Advanced Vasodilatory Shock: A Prospective, Randomized, Controlled Study

2003

PMID 12732600

Population / Model
N=48, advanced vasodilatory shock
Dose / Duration / Finding

Arginine vasopressin infusion produced measurable hemodynamic effects in advanced vasodilatory shock in a controlled human trial.

PubMed

Effect of chronic low-dose arginine vasopressin infusion on body fluid homoeostasis during adaptation from a high- to a low-sodium diet in normal man

1993

PMID 8222513

Population / Model
Healthy human volunteers
Dose / Duration / Finding

Constant low-dose AVP infusion (6 fmol/min/kg) blunted the natural diuresis and blunted the rise in plasma renin activity that otherwise accompanies dietary sodium restriction.

PubMed

Animal / Cell / Preclinical Data

No Animal / Cell / Preclinical Data Listed Yet

This section will be updated as sources are added.

Regulatory Documents & Official Trial Registries(1)

FDA Label / DailyMed Record for Vasostrict (Vasopressin Injection)

Population / Model
Dose / Duration / Finding

Vasostrict (vasopressin injection) is a sterile aqueous solution of synthetic arginine vasopressin, exact 9-residue AVP sequence (Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2, cyclo 1-6), FDA-approved to increase blood pressure in adults with vasodilatory shock (e.g., post-cardiotomy or sepsis) who remain hypotensive despite fluids and catecholamines. Labeled dosing 0.01-0.07 units/min titration.

Show full finding

Safety note

Labeled adverse-event profile includes bradycardia, tachyarrhythmia, hyponatremia, and coronary/mesenteric/skin/digital ischemia.

No source link available

Anecdotal Reported Patterns — Not Medical Advice

Anecdotal Reported Patterns — Not Medical Advice

Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.

Lab Markers to Discuss With a Clinician

Educational topics only — not self-monitoring instructions.

FAQ

Yes. 'Vasopressin,' 'Antidiuretic Hormone (ADH),' and 'Arginine Vasopressin (AVP)' all refer to the same mature 9-amino-acid hormone in humans; these are interchangeable functional/generic names, not different molecules.

Disclaimer

Educational information only. This page summarizes published research and official regulatory information about Arginine Vasopressin and does not provide medical advice, an individualized treatment recommendation, or dosing instructions.

Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.

Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.

Content status: Published. Last updated .

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