Evidence Snapshot
What this grade covers
Applies to direct, controlled human Angiotensin I infusion evidence only (PMID 10826400, N=10; PMID 9683924). This is real, not absent, evidence — both are genuine controlled human intravenous infusion studies, not case reports or animal work — but it is narrow (two studies, both mechanistic/dose-response physiology in small numbers of healthy or sodium-restricted volunteers, no RCT of Angiotensin I as a therapeutic intervention, no disease-outcome trial of any kind) and its own central finding is that Angiotensin I's measured pressor/aldosterone effects are mediated entirely through ACE-dependent conversion to Angiotensin II, not through any independent Angiotensin-I-receptor-mediated action of its own. This grade explicitly does NOT borrow strength from Angiotensin II's evidence base (native or Giapreza-related), from Angiotensin-(1-7)'s evidence base, or from the much larger general ACE-inhibitor clinical-trial literature, none of which is direct Angiotensin I evidence. 'D+' rather than a flat 'D' or 'C-' reflects that the existing evidence, while narrow, is genuinely well-controlled human physiology data (not merely preclinical or anecdotal) and directly answers the mechanistic question of interest (is there an independent Ang I effect) rather than leaving it unaddressed.
Regulatory Context
Angiotensin I has no FDA-approved or other major-regulator-approved therapeutic status identified in this review; it is studied and understood exclusively as an endogenous intermediate of the renin-angiotensin-aldosterone system.
Research Takeaway
Angiotensin I is the inactive decapeptide precursor cleaved from angiotensinogen by renin, and is itself the direct substrate that angiotensin-converting enzyme (ACE) cleaves to form the active octapeptide Angiotensin II.
See all 5 evidence claims →Quick Summary
Angiotensin I is the inactive precursor peptide that angiotensin-converting enzyme (ACE) converts into the active hormone Angiotensin II. Its strongest direct human evidence comes from a small number of controlled infusion studies showing that its physiological effects depend entirely on this conversion — no independent receptor-mediated action of Angiotensin I itself has been demonstrated in the human evidence reviewed, and it has no approved therapeutic product of its own.
Mechanism & Research Overview
Angiotensin I is the inactive precursor peptide that angiotensin-converting enzyme (ACE) converts into the active hormone Angiotensin II. Its strongest direct human evidence comes from a small number of controlled infusion studies showing that its physiological effects depend entirely on this conversion — no independent receptor-mediated action of Angiotensin I itself has been demonstrated in the human evidence reviewed, and it has no approved therapeutic product of its own.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
Angiotensin I is the inactive decapeptide precursor cleaved from angiotensinogen by renin, and is itself the direct substrate that angiotensin-converting enzyme (ACE) cleaves to form the active octapeptide Angiotensin II.
Sources: Effect of ACE inhibition on pressor, renal vascular, and adrenal responses to infusion of angiotensin I in normal subjects eating a low-salt diet; Dissociation between the renal effects of angiotensin I and II in sodium-restricted normal subjects
Supported
In controlled human intravenous infusion studies, Angiotensin I raises blood pressure and plasma aldosterone in a dose-dependent manner, but ACE inhibition abolishes this effect at low and moderate Angiotensin I doses, and only a high dose still produces a measurable response by generating enough residual Angiotensin II to do so.
Supported
No study identified in this review demonstrates an independent, ACE-conversion-independent pharmacological effect of Angiotensin I in humans; its measured physiological effects are explained by its conversion to Angiotensin II, not by direct action of Angiotensin I itself on a receptor of its own.
Does not establish
Evidence boundary: This is a boundary statement about the existing evidence, not an absolute claim that no Angiotensin I receptor-mediated activity could ever be found; it reflects what the direct human evidence in this manifest actually shows.
Sources: Effect of ACE inhibition on pressor, renal vascular, and adrenal responses to infusion of angiotensin I in normal subjects eating a low-salt diet; Dissociation between the renal effects of angiotensin I and II in sodium-restricted normal subjects
Supported
Angiotensin I's direct human evidence base is substantially narrower than Angiotensin II's; general ACE-inhibitor clinical-outcome trials and general RAAS-physiology reviews are not direct Angiotensin I evidence and must not be used to imply a larger or more clinically established Angiotensin I evidence base than the two direct-infusion studies in this manifest actually support.
Supported
Angiotensin I has no FDA-approved or other major-regulator-approved therapeutic product of its own identified in this review; it functions exclusively as an endogenous intermediate in the renin-angiotensin-aldosterone system.
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
Any future content must not imply Angiotensin I has an established, clinically meaningful, ACE-independent action; the direct evidence shows the opposite.Safety Consideration
Only two controlled human infusion studies exist in this manifest, both small, both physiology-only, no disease-outcome or therapeutic trial.Safety Consideration
The much larger ACE-inhibitor clinical-trial and general RAAS-review literature must not be cited as if it were direct Angiotensin I evidence in any future implementation.
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.
- Effect of ACE inhibition on pressor, renal vascular, and adrenal responses to infusion of angiotensin I in normal subjects eating a low-salt diet (2000):
- Dissociation between the renal effects of angiotensin I and II in sodium-restricted normal subjects (1998):
Study Tables by Evidence Type
Human Studies & Clinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Effect of ACE inhibition on pressor, renal vascular, and adrenal responses to infusion of angiotensin I in normal subjects eating a low-salt diet | 2000 | 10 normotensive healthy men, low-salt diet, studied before and during ACE inhibition with enalapril; Angiotensin I infused at 3, 10, and 30 ng/kg/min | ACE inhibition abolished the pressor/aldosterone response to low/mid-dose Angiotensin I; only the highest dose (30 ng/kg/min) still raised plasma Angiotensin II and produced a pressor/aldosterone response, tracking the residual Angiotensin II formed — i.e., Angiotensin I's measured effects are mediated entirely through ACE-dependent conversion to Angiotensin II. | ||
| Dissociation between the renal effects of angiotensin I and II in sodium-restricted normal subjects | 1998 | Sodium-restricted normal human subjects; Angiotensin I and Angiotensin II separately infused and directly compared | Angiotensin I and Angiotensin II produce dissociable renal effects under sodium restriction — direct evidence that Angiotensin I's renal actions are not a simple proxy for Angiotensin II's. |
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
No Regulatory Documents & Official Trial Registries Listed Yet
This section will be updated as sources are added.
Review Articles / Secondary Sources
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Angiotensin-converting enzyme inhibitors. Relationship between pharmacodynamics and pharmacokinetics | General ACE-inhibitor pharmacodynamics/pharmacokinetics review; discovery/context tier only. |
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
Disclaimer
Educational information only. This page summarizes published physiology research about Angiotensin I 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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