Compounds with a graded row

Ordered by rung, strongest first. The rung rates the study design; the chip beside it says what the study measured. Both are needed.

1. Adrenomedullin

   human RCT Direct outcome Not approved for this condition

   Who was studied

   men aged 39-58 with uncomplicated essential hypertension, baseline 147/96 mmHg, n=8; two-hour infusions in a placebo-controlled crossover

   Blood pressure was measured in hypertensive men during intravenous adrenomedullin: the high dose (5.8 pmol/kg/min for 2 hours) lowered systolic by 24.6 mmHg and diastolic by 21.9 mmHg against vehicle, with a rise in heart rate and cardiac output. This is an acute infusion study of an endogenous peptide, not a treatment course; no trial of repeated or oral administration for hypertension is on file.

   Source PubMed 1 primary source read for this row

2. Apelin

   human RCT Direct outcome Not approved for this condition

   Who was studied

   chronic heart failure patients NYHA II-III (n=18), patients undergoing diagnostic coronary angiography (n=6) and healthy volunteers (n=26); hypertension status of participants is not reported and no hypertensive cohort was enrolled

   Mean arterial pressure was measured in humans during systemic infusion of (Pyr1)apelin-13 in a randomised, double-blind, placebo-controlled study and fell in both heart failure patients and healthy controls, with peripheral and coronary vasodilatation and a rise in cardiac output. The trial was designed around heart failure: no hypertensive population was studied, and the infusions were acute, lasting minutes.

   Source PubMed 1 primary source read for this row

3. Atrial Natriuretic Peptide (ANP)

   human RCT Direct outcome Not approved for this condition

   Who was studied

   patients with essential hypertension, n=6, single intravenous injection; normotensive volunteers studied for comparison

   Arterial pressure was measured in humans after a 100 microgram intravenous injection of alpha-human atrial natriuretic peptide in a double-blind, placebo-controlled study: pressure fell within 2 minutes and had returned to placebo levels by 10 minutes, while urinary sodium excretion rose sixfold over 30 minutes. The blood pressure effect in the hypertensive patients was less sustained than the renal effect, and no trial of ANP given for the ongoing treatment of hypertension is on file.

   Source PubMed 1 primary source read for this row

4. C-Type Natriuretic Peptide (CNP)

   human RCT Direct outcome Not approved for this condition

   Who was studied

   healthy normotensive volunteers, mean age 33, n=6; two one-hour infusions at 2 and 4 pmol/kg per minute

   Arterial pressure was measured in humans and did not move. Infusion raised plasma CNP from 1.17 to 41.52 pmol/L, four to ten times the levels seen in disease, with no effect on arterial pressure, cardiac output, cardiac volumes, renal haemodynamics, sodium excretion, plasma or urinary cGMP, renin or aldosterone. The authors conclude the result does not support CNP acting as a circulating hormone in humans. The population was normotensive, so this measures whether CNP lowers pressure at all rather than whether it treats hypertension, and no trial in a hypertensive population is on file. The animal record agrees rather than contradicting it: in hypertensive transgenic rats carrying an extra mouse renin gene (PubMed 8986453), atrial and brain natriuretic peptide each lowered blood pressure in one strain or the other and CNP lowered it in neither, alone or with a neutral endopeptidase inhibitor. Rung set from the study's own design wording, "random-order".

   Source PubMed 2 primary sources read for this row

5. Endothelin-1

   human RCT Direct outcome Not approved for this condition

   Who was studied

   ten healthy male volunteers, studied on two occasions; systemic infusions of endothelin-1 at 0.75, 1.5 and 3 pmol/kg per minute for 30 minutes each against saline

   Vascular resistance was measured in humans and rose. Systemic vascular resistance went from 1156 to 1738 dyn.s.cm-5 and total pulmonary vascular resistance from 142 to 329, with dose-related falls in heart rate, stroke volume and cardiac output. This row records a compound that RAISES vascular resistance, the opposite of what a hypertension treatment does. It is on file because the measurement is a direct one in humans and because the finding is the reason endothelin receptor antagonists, not endothelin-1, are the drugs in this indication. No study has administered endothelin-1 to lower blood pressure. Rung set from the study's own design wording, "randomised, double-blind, placebo-controlled".

   Source PubMed 1 primary source read for this row

6. Soy Peptides

   human RCT Direct outcome Not approved for this condition

   Who was studied

   adults with untreated systolic 130-159 mmHg and/or diastolic 80-99 mmHg (prehypertension to stage 1 hypertension), n=100, 8 weeks

   Office blood pressure was measured in humans: 4.5 g of black soy peptides daily for 8 weeks was followed by a systolic fall of -9.69 +/- 12.37 mmHg against -2.91 +/- 13.29 mmHg on placebo, alongside changes in malondialdehyde, superoxide dismutase and nitric oxide. The enrolled population was hypertensive rather than normotensive. No regulator has approved soy peptides for hypertension.

   Source PubMed 1 primary source read for this row

7. Angiotensin I

   human observational Direct outcome Not approved for this condition

   Who was studied

   healthy men of ACE genotype DD (n=8) and II (n=8); incremental intravenous infusion of angiotensin I titrated to a 25 mmHg rise in diastolic and in systolic pressure

   Blood pressure was measured in humans and rose, which is the intended effect of the infusion rather than a side effect. The infusion is titrated upwards until diastolic pressure has risen by 25 mmHg, and the dose needed is the result being reported: a geometric mean of 2.53 micrograms per minute in II subjects and 2.67 in DD, a ratio of 0.95 with a confidence interval from 0.44 to 2.02, despite serum converting-enzyme activity differing nearly fourfold between the genotypes. A second infusion study in ten normotensive men (PubMed 10826400) found the pressor and aldosterone responses fell in proportion to the reduction in angiotensin II formation under ACE inhibition, while the renal response was inhibited substantially less than expected — read by its authors as angiotensin I being converted to angiotensin II inside the kidney rather than only in the lung. Angiotensin I raises blood pressure, so it is the opposite of a hypertension treatment, and this row exists to record that fact with a measurement behind it. It is a research probe of converting-enzyme activity, nothing in the record proposes it as a therapy, and neither study followed a clinical outcome beyond the session. Rung set by review: sixteen healthy men in two groups compared by ACE genotype — a comparison nobody can randomise.

   Source PubMed 2 primary sources read for this row

8. Angiotensin (1-7)

   human case series Surrogate marker Not approved for this condition

   Who was studied

   patients with essential hypertension (n=8) and normotensive controls (n=8); intra-arterial infusion into the brachial artery, 5 minutes per dose, not randomised and not placebo-controlled

   What was measured was forearm blood flow by venous occlusion plethysmography, which rose dose-dependently by about 32% in the hypertensive patients and about 29% in the controls; systemic blood pressure was not the outcome, and a local vasodilator response in one limb is not a blood pressure result. No study on file measured office, ambulatory or home blood pressure in people given angiotensin-(1-7).

   Source PubMed 1 primary source read for this row

9. Neurotensin

   animal in vivo Direct outcome Not approved for this condition

   Who was studied

   anaesthetised normotensive rats; intrathecal administration, 0.5 micromolar to 3 millimolar, acute recording only

   Mean arterial pressure was measured directly in anaesthetised rats and fell dose-dependently, to about -25 mmHg at 3 mM, with bradycardia and reduced sympathetic nerve activity. The animals were normotensive and the peptide was placed into the intrathecal space rather than given systemically, so this is spinal cardiovascular physiology; no study measured blood pressure in a hypertensive animal model or in any human given neurotensin.

   Source PubMed 1 primary source read for this row

10. Wheat Peptides

    animal in vivo Direct outcome Not approved for this condition

    Who was studied

    spontaneously hypertensive rats; group sizes, dose and dosing duration are not stated in the abstract and the full text is paywalled

    Systolic, diastolic and mean arterial pressure were measured in living spontaneously hypertensive rats and fell after wheat oligopeptides; the same paper reports 77% ACE inhibition at 2.5 mg/mL in a test tube, which is a separate in vitro result. No study measuring blood pressure in humans given wheat-derived peptides was located: the registered trial NCT02197910 posted no results and no publication was found, so the human blood-pressure claim remains a named gap and this row is rat evidence only.

    Source PubMed 1 primary source read for this row

Recorded absences

3 compounds are listed here without a rung. Each row exists to mark a distinction a reader would otherwise draw wrongly, and each says what is missing rather than leaving the compound off the page.

1. CRH (Corticotropin-Releasing Hormone)

   No rung — nothing on file to grade Not approved for this condition

   A CRH test transiently raises cortisol and can raise blood pressure. It is never given to lower it and no trial has tried.

2. Hexarelin

   No rung — nothing on file to grade Not approved for this condition

   No trial has used this compound against this condition. The only blood-pressure-adjacent finding retrieved is in vitro inhibition of angiotensin-converting enzyme by hexarelin in an assay, with no blood pressure measured in any hypertensive population.

3. Vasopressin

   No rung — nothing on file to grade Not approved for this condition

   Vasopressin raises blood pressure; it is given as a pressor in vasodilatory shock. No trial has administered it to lower blood pressure, and none is expected to.