Evidence map›Paper›PMID 19841473›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2010

Endogenous nitric oxide contributes to bradykinin-stimulated glucose uptake but attenuates vascular tissue-type plasminogen activator release.

Mias Pretorius, Nancy J Brown

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00685945 (Renin-Angiotensin Aldosterone System and Fibrinolysis), which is not on this map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 32% 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.

NCT00685945 nacompletednot on this map

Renin-Angiotensin Aldosterone System and Fibrinolysis(RAAS) Interaction in Humans- Specific Aim 3

TypeinterventionalSponsorVanderbilt UniversityRan2007 to 2009Enrolled24ConditionsObesityArmsControl (bradykinin), L-NMMA + bradykinin, Isosorbide + L-NMMA + bradykinin, Sildenafil + L-NMMA + bradykinin
3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. The Vasculature in Prediabetes.Circulation research · 2018
    Review
  6. Article
  7. Article
  8. Vascular Nitric Oxide: Formation and Function.Journal of blood medicine · 2010
    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

2 authors at 1 institution in 1 country.

Mias PretoriusDepartment of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. mias.pretorius@vanderbilt.edu
Nancy J Brown
Vanderbilt University · US

Funding

VANDERBILT UNIVERSITY CTSA FOR PEDIATRIC RESEARCHUL1RR024975 · NCRR · VANDERBILT UNIVERSITY · PI BERNARD, GORDON RAPHAEL · 2007 to 2011
$45.7M
RENIN/ANGIOTENSIN SYSTEM AND FIBRINOLYSIS IN HUMANSR01HL060906 · NHLBI · VANDERBILT UNIVERSITY · PI BROWN, NANCY J. · 1998 to 2014
$5.4M
GENES AND FIBRINOLYTIC CAPACITY OF HUMAN ENDOTHELIUMR01HL065193 · NHLBI · VANDERBILT UNIVERSITY · PI IKIZLER, TALAT ALP, PRETORIUS, MIAS · 2000 to 2012
$4.0M
Bradykinin Receptor Antagonism During Cardiopulmonary BypassR01HL085740 · NHLBI · VANDERBILT UNIVERSITY · PI PRETORIUS, MIAS · 2006 to 2010
$2.0M
NCRR NIH HHS 1UL1-RR024975NCRR NIH HHS UL1 RR024975NHLBI NIH HHS HL060906NHLBI NIH HHS HL065193NHLBI NIH HHS HL085740NHLBI NIH HHS R01 HL060906NHLBI NIH HHS R01 HL065193NHLBI NIH HHS R01 HL085740
6 · The paper itself

Abstract

Bradykinin causes vasodilation, stimulates tissue-type plasminogen activator (t-PA) release and, in rodents, increases muscle glucose uptake. Although bradykinin causes vasodilation partly by activating nitric-oxide synthase (NOS), the role of nitric oxide in regulating bradykinin-stimulated t-PA release is uncertain. This study examined the effect of high-dose NOS inhibition on bradykinin-stimulated t-PA release and glucose uptake in humans. We studied 24 healthy (12 women and 12 men), overweight and obese (body mass index >25 kg/m(2)), normotensive, nondiabetic subjects with normal cholesterol. We measured the effect of intra-arterial N(omega)-monomethyl-L-arginine (L-NMMA, 12 micromol/min) on forearm blood flow (FBF), net t-PA release, and glucose uptake at baseline and in response to intra-arterial bradykinin (50-200 ng/min) in subjects pretreated with the cyclooxygenase inhibitor aspirin. Measurements were repeated after isosorbide dinitrate (ISDN; 5 mg) or sildenafil (50 mg). L-NMMA decreased baseline FBF (P < 0.001), increased baseline forearm vascular resistance (P < 0.001), and increased the t-PA arterial-venous gradient (P = 0.04) without affecting baseline net t-PA release or glucose uptake. During L-NMMA, ISDN tended to decrease baseline net t-PA release (P = 0.06). L-NMMA blunted bradykinin-stimulated vasodilation (P < 0.001 for FBF and FVR). Bradykinin increased net glucose extraction (from -80 +/- 23 to -320 +/- 97 microg/min/100 ml at 200 ng/min bradykinin, P = 0.02), and L-NMMA (-143 +/- 50 microg/min/100 ml at 200 ng/min, P = 0.045) attenuated this effect. In contrast, L-NMMA enhanced bradykinin-stimulated t-PA release (39.9 +/- 7.0 ng/min/100 ml versus 30.0 +/- 4.2 ng/min/100 ml at 200 ng/min, P = 0.04 for L-NMMA). In gender-stratified analyses, L-NMMA significantly increased bradykinin-stimulated t-PA release in women (F = 6.7, P = 0.02) but not in men. Endogenous NO contributes to bradykinin-stimulated vasodilation and glucose uptake but attenuates the fibrinolytic response to exogenous bradykinin.

Indexed as

AdultAspirinBradykininDose-Response Relationship, DrugEndothelium, VascularEnzyme InhibitorsFemaleForearmGlucoseHumansMaleNitric OxideNitric Oxide DonorsNitric Oxide SynthaseObesityomega-N-MethylarginineAspirinBradykininEnzyme InhibitorsGlucoseNitric OxideNitric Oxide DonorsNitric Oxide Synthaseomega-N-MethylarginineTissue Plasminogen Activator

Identifiers

PMID19841473
PMCPMC2802470
OpenAlexW2126011998

What Socratic holds

Textmetadata
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.