ArticleArteriosclerosis, thrombosis, and vascular biology2020
Acetaminophen (Paracetamol) Metabolites Induce Vasodilation and Hypotension by Activating Kv7 Potassium Channels Directly and Indirectly.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Hemodynamic Effects of Anesthetics, Sedatives, and Analgesics in the CICU: Clinical Decision Guidance.JACC. Advances · 2026Review
- Intravenous paracetamol does not have significant opioid-sparing effects when used as part of a multimodal analgesic protocol in dogs undergoing elective orthopaedic surgery.The Veterinary record · 2026Article
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Personalized Multimodal and Opioid-Sparing Analgesia for Postoperative Pain Management: Enhancing Recovery and Addressing the Post-Discharge Gap.Journal of pain research · 2026Review
- Effects of a novel acetaminophen analog on cardiorespiratory compensatory responses and survival in a male rat model of traumatic hemorrhage.Physiological reports · 2025Article
- Risk Factors for Serious Hypotension Induced by Intravenous Acetaminophen in Patients With Hematologic Malignancy.Pharmacoepidemiology and drug safety · 2025Article
- Vasorelaxant effects of 3-methoxycatechol are not via direct activation of voltage-gated potassium channels.Vascular pharmacology · 2025Article
- Anaesthetic management and peri-operative complications in dogs undergoing cardiac electrophysiology studies and radio-frequency catheter ablations.Frontiers in veterinary science · 2025Article
- Risk Factors for Intravenous Acetaminophen-Induced Hypotension in Patients with Repeated Acetaminophen Administration.Yonsei medical journal · 2024Observational
- Crucial role for sensory nerves and Na/H exchanger inhibition in dapagliflozin- and empagliflozin-induced arterial relaxation.Cardiovascular research · 2024Article
- Potential Therapeutic Targets for Hypotension in Duchenne Muscular Dystrophy.Medical hypotheses · 2024Article
- Proximity Labelling to Quantify Kv7.4 and Dynein Protein Interaction in Freshly Isolated Rat Vascular Smooth Muscle Cells.Bio-protocol · 2024Article
- Dehydroepiandrosterone Sulfate (DHEAS) Is an Endogenous Kv7 Channel Modulator That Reduces Kv7/M-Current Suppression and Inflammatory Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The Three W's of Acetaminophen In Children: Who, Why, and Which Administration Mode.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2023Article
- 7-Hydroxycoumarin Induces Vasorelaxation in Animals with Essential Hypertension: Focus on Potassium Channels and Intracellular CaMolecules (Basel, Switzerland) · 2022Article
- Acetaminophen treatment evokes anticontractile effects in rat aorta by blocking L-type calcium channels.Pharmacological reports : PR · 2022Article
- Risk Factors for Intravenous Propacetamol-Induced Blood Pressure Drop in the Neurointensive Care Unit: A Retrospective Observational Study.Neurocritical care · 2022Observational
- Acetaminophen-induced hypotension in sepsis.Journal of pharmaceutical health care and sciences · 2022Article
- Fever: Could A Cardinal Sign of COVID-19 Infection Reduce Mortality?The American journal of the medical sciences · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectiveIntravenous acetaminophen/paracetamol (APAP) is well documented to cause hypotension. Since the patients receiving intravenous APAP are usually critically ill, any severe hemodynamic changes, as with those associated with APAP, can be life-threatening. The mechanism underlying this dangerous iatrogenic effect of APAP was unknown. Approach and Results: Here, we show that intravenous APAP caused transient hypotension in rats, which was attenuated by the Kv7 channel blocker, linopirdine. APAP metabolite N-acetyl-p-benzoquinone imine caused vasodilatation of rat mesenteric arteries ex vivo. This vasodilatation was sensitive to linopirdine and also the calcitonin gene-related peptide antagonist, BIBN 4096. Further investigation revealed N-acetyl-p-benzoquinone imine stimulates calcitonin gene-related peptide release from perivascular nerves, causing a cAMP-dependent activation of Kv7 channels. We also show that N-acetyl-p-benzoquinone imine enhances Kv7.4 and Kv7.5 channels overexpressed in oocytes, suggesting that it can activate Kv7.4 and Kv7.5 channels directly, to elicit vasodilatation.
conclusionsDirect and indirect activation of Kv7 channels by the APAP metabolite N-acetyl-p-benzoquinone imine decreases arterial tone, which can lead to a drop in blood pressure. Our findings provide a molecular mechanism and potential preventive intervention for the clinical phenomenon of intravenous APAP-dependent transient hypotension.
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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 OpenQuestion graph.