Evidence mapPaperPMID 24516103Full record

Trial reportHypertension (Dallas, Tex. : 1979)2014

Substance P increases sympathetic activity during combined angiotensin-converting enzyme and dipeptidyl peptidase-4 inhibition.

Jessica K Devin, Mias Pretorius, Hui Nian, Chang Yu, Frederic T Billings, Nancy J Brown

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Hypertension (Dallas, Tex. : 1979), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01413542 (Pharmacogenetics of Ace Inhibitor-Associated Angioedema), which is not on this map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
6.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01413542 nacompletednot on this map

Pharmacogenetics of Ace Inhibitor-Associated Angioedema:Aim 1

TypeinterventionalSponsorVanderbilt UniversityRan2011 to 2014Enrolled44ConditionsHypertension, Diabetes Type 2ArmsSitagliptin (DPP4 inhibitor), Substance P,, bradykinin, enalaprilat (ACE inhibitor), Glucagon-like peptide 1
3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Trial
  6. Effect of Linagliptin on Vascular Function: A Randomized, Placebo-controlled Study.The Journal of clinical endocrinology and metabolism · 2016
    Trial
  7. Trial
  8. Article
  9. Review
  10. DPP4 as a Potential Candidate in Cardiovascular Disease.Journal of inflammation research · 2022
    Review
  11. Article
  12. DPP4 Inhibition, NPYThe Journal of pharmacology and experimental therapeutics · 2020
    Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Observational
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Jessica K DevinDivision of Diabetes, Endocrinology and Metabolism, 7465 MRB4, 2213 Garland Ave, Nashville, TN 37232. Jessica.devin@vanderbilt.edu.
Mias Pretorius
Hui Nian
Chang Yu
Frederic T Billings
Nancy J Brown
Vanderbilt University Medical Center · US

Funding

RENIN/ANGIOTENSIN SYSTEM AND FIBRINOLYSIS IN HUMANSR01HL060906 · VANDERBILT UNIVERSITY · 1998 to 2005
$2.0M
Pharmacogenetics of ACE inhibitor-associated angioedemaR01HL079184 · VANDERBILT UNIVERSITY · 2005 to 2005
$338k
NCATS NIH HHS UL1 TR000445NHLBI NIH HHS HL060906NHLBI NIH HHS K23 HL119602NHLBI NIH HHS R01 HL060906NHLBI NIH HHS R01 HL079184NHLBI NIH HHS R01HL079184NIGMS NIH HHS 5P30GM092386NIGMS NIH HHS K23 GM102676NIGMS NIH HHS K23GM102676NIGMS NIH HHS P30 GM092386
6 · The paper itself

Abstract

unlabelledDipeptidyl peptidase-4 inhibitors prevent the degradation of incretin hormones and reduce postprandial hyperglycemia in patients with type 2 diabetes mellitus. Dipeptidyl peptidase-4 degrades other peptides with a penultimate proline or alanine, including bradykinin and substance P, which are also substrates of angiotensin-converting enzyme (ACE). During ACE inhibition, substance P is inactivated primarily by dipeptidyl peptidase-4, whereas bradykinin is first inactivated by aminopeptidase P. This study tested the hypothesis that dipeptidyl peptidase-4 inhibition potentiates vasodilator and fibrinolytic responses to substance P when ACE is inhibited. Twelve healthy subjects participated in this randomized, double-blinded, placebo-controlled crossover study. On each study day, subjects received sitagliptin 200 mg by mouth or placebo. Substance P and bradykinin were infused via brachial artery before and during intra-arterial enalaprilat. Sitagliptin and enalaprilat each reduced forearm vascular resistance and increased forearm blood flow without affecting mean arterial pressure, but there was no interactive effect of the inhibitors. Enalaprilat increased bradykinin-stimulated vasodilation and tissue plasminogen activator release; sitagliptin did not affect these responses to bradykinin. The vasodilator response to substance P was unaffected by sitagliptin and enalaprilat; however, substance P increased heart rate and vascular release of norepinephrine during combined ACE and dipeptidyl peptidase-4 inhibition. In women, sitagliptin diminished tissue plasminogen activator release in response to substance P both alone and during enalaprilat. Substance P increases sympathetic activity during combined ACE and dipeptidyl peptidase-4 inhibition. CLINICAL

trial registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01413542.

Indexed as

AdultAngiotensin-Converting Enzyme InhibitorsBlood PressureBradykininCross-Over StudiesDipeptidyl Peptidase 4Double-Blind MethodEnalaprilatEnzyme InhibitorsFemaleHeart RateHumansMaleMiddle AgedNeurotransmitter AgentsNorepinephrineAngiotensin-Converting Enzyme InhibitorsBradykininDipeptidyl Peptidase 4DPP4 protein, humanEnalaprilatEnzyme InhibitorsNeurotransmitter AgentsNorepinephrinePeptidyl-Dipeptidase APyrazinesSitagliptin PhosphateSubstance PTriazolesdiabetes mellitusdipeptidyl peptidase-4hypertensionnorepinephrinerenin–angiotensin systemvasodilation

Identifiers

PMID24516103
PMCPMC3984385
OpenAlexW2124761610

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.