Evidence map›Paper›PMID 42334380›Full record

ArticleCardiovascular research2026

Carbon dioxide is a triple vasodilator.

Dragos A Duse, Nathalie H Schröder, Sotirios Akritidis, Julia Kälsch, Dorothe Möllmann, Martin Schlattjan, Julia Hoppe, Evanthia Mergia, Martin Lainka, Kurt W Schmid and 9 more

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In one paragraph

Article in Cardiovascular research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

19 authors.

Dragos A DuseInstitute for Molecular Medicine III, University Hospital Düsseldorf, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany.ORCID 0000-0003-0127-1016
Nathalie H SchröderInstitute for Molecular Medicine III, University Hospital Düsseldorf, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Sotirios AkritidisDivision of Vascular and Endovascular Surgery, Department of General, Visceral, Vascular and Transplantation Surgery, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.
Julia KälschDepartment of Gastroenterology and Hepatology, University Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.
Dorothe MöllmannInstitute of Pathology, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.
Martin SchlattjanInstitute of Pathology, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.
Julia HoppeInstitute for Molecular Medicine III, University Hospital Düsseldorf, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Evanthia MergiaInstitute of Pharmacology and Toxicology, Ruhr-University Bochum, Universitätsstrasse 150, 44780 Bochum, Germany.
Martin LainkaDivision of Vascular and Endovascular Surgery, Department of General, Visceral, Vascular and Transplantation Surgery, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.
Kurt W SchmidInstitute of Pathology, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.
Sylvia HartmannInstitute of Pathology, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.
Christoph M SchaeferInstitute of Pathology, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.
Finn WichmannInstitute of Pathology, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.
Amin PolzinDepartment of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich Heine University, Moorenstraße 5, 40225 Düsseldorf, Germany.
Ralf ErkensDepartment of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich Heine University, Moorenstraße 5, 40225 Düsseldorf, Germany.
Christian JungDepartment of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich Heine University, Moorenstraße 5, 40225 Düsseldorf, Germany.ORCID 0000-0001-8325-250X
Malte KelmDepartment of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich Heine University, Moorenstraße 5, 40225 Düsseldorf, Germany.ORCID 0000-0003-0060-1052
Bodo LevkauInstitute for Molecular Medicine III, University Hospital Düsseldorf, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, Germany.ORCID 0000-0002-0005-125X
Hideo A BabaInstitute of Pathology, University of Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany.ORCID 0000-0002-1750-5318

Funding

DFG SFB TRR259
6 · The paper itself

Abstract

aimsCarbon dioxide (CO2) can regulate blood flow and is applied therapeutically in intensive care units to treat brain injury, as well as in balneotherapy for peripheral arterial disease (PAD) and diabetic angiopathy; however, its mode of action remains unclear. METHODS AND

resultsThe vasoactive CO2 effects were tested in arteries of healthy C57BL/6J mice, hypertensive apolipoprotein E-deficient mice, and soluble guanylyl cyclase (sGC) knockout mice in a small vessel myograph with and without pharmacologically intervening in endothelium- and/or vascular smooth muscle-mediated vasodilation. CO2-based near-infrared spectroscopy (NIRS-CO2) was developed to assess vasoreactivity of the skin microcirculation to CO2 in healthy individuals, PAD and coronary artery disease (CAD) patients, and was compared with flow-mediated dilation (FMD). We identified CO2 as a triple vasodilator mimicking the actions of endothelium-derived relaxing factor (nitric oxide, NO), endothelium-derived hyperpolarization factor, and direct myogenic vasodilators. CO2 engaged endothelial NO/sGC, endothelial small-/intermediate-conductance calcium-activated potassium channels (SKCa/IKCa), and myogenic voltage-gated (KV) and IKCa potassium channels, respectively, acting as a triple vasodilator. CO2-evoked vasodilator responses were blunted and delayed in diseased human and murine arteries. In the human cohort, the NIRS-CO2-derived time-to-intersection of the HbO2 and HHb curves, capturing the delay phenotype, showed a strong association with PAD/CAD status and, in exploratory analyses, also distinguished young individuals with cardiovascular risk factors, supporting NIRS-CO2 as a physiological readout that integrates endothelial and myogenic components of microvascular reactivity. Duration and extent of CO2 vasodilation were coupled to tissue metabolism through vascular carbonic anhydrases (CAs), providing a mechanism for vasculometabolic coupling and one for clinically approved CA inhibitors.

conclusionNIRS-CO2 provides a feasible readout of CO2-evoked microvascular responsiveness and shows disease-associated alterations in our PAD/CAD cohort. Larger studies will validate generalizability across vasculopathies and clarify the relative contributions of NO-sGC vs. K+ channel-linked mechanisms for future therapeutic translation.

Indexed as

ArteriesCarbon DioxidePeripheral Arterial DiseaseSkinVasodilationVasodilator AgentsAnimalsBiological FactorsDisease Models, AnimalEndothelium, VascularFemaleHumansIntermediate-Conductance Calcium-Activated Potassium ChannelsMaleMice, Inbred C57BLMice, Knockout, ApoEBiological FactorsCarbon Dioxideendothelium-dependent hyperpolarization factorIntermediate-Conductance Calcium-Activated Potassium ChannelsNitric OxideSmall-Conductance Calcium-Activated Potassium ChannelsSoluble Guanylyl CyclaseVasodilator AgentsCarbon dioxideCarbonic anhydraseEndothelium-derived hyperpolarizationNear-infrared spectroscopyNitric oxidePeripheral artery diseasePotassium channels

Identifiers

PMID42334380
PMCPMC13473971

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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 OpenQuestion graph.