ArticleAmerican journal of physiology. Heart and circulatory physiology2006
Epoxyeicosatrienoic and dihydroxyeicosatrienoic acids dilate human coronary arterioles via BK(Ca) channels: implications for soluble epoxide hydrolase inhibition.
Article in American journal of physiology. Heart and circulatory physiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 169 citations in OpenAlex.
- General View of Arachidonic Acid (AA) Metabolism.Reviews of physiology, biochemistry and pharmacology · 2027Review
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- Microbiota-derived metabolites in hematopoietic regulation and disease: mechanisms, context, and therapeutic perspectives.Frontiers in microbiology · 2026Review
- Regulation of P450-derived epoxy fatty acids in cardiovascular diseases.Redox biochemistry and chemistry · 2025Article
- Effect of Season on Testicular Development and Spermatogenesis in Hu Sheep: Insights from Antioxidant Indices, Oxylipins, and Transcriptomics.Animals : an open access journal from MDPI · 2025Article
- Influence of TrimethylamineNutrients · 2022Article
- Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease.International journal of molecular sciences · 2021Review
- Cyp2c44 epoxygenase-derived epoxyeicosatrienoic acids in vascular smooth muscle cells elicit vasoconstriction of the murine ophthalmic artery.Scientific reports · 2021Article
- Regulation of cardiovascular biology by microsomal epoxide hydrolase.Toxicological research · 2021Review
- Coronary Large Conductance CaFrontiers in physiology · 2021Review
- Neurovascular Coupling in Development and Disease: Focus on Astrocytes.Frontiers in cell and developmental biology · 2021Review
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- Crossing signals: bioactive lipids in the microvasculature.American journal of physiology. Heart and circulatory physiology · 2020Review
- Missense Genetic Polymorphisms of Microsomal (Neuropsychiatric disease and treatment · 2020Article
- Circadian Variation in Vasoconstriction and Vasodilation Mediators and Baroreflex Sensitivity in Hypertensive Rats.Journal of circadian rhythms · 2019Article
- Emerging role of 12/15-Lipoxygenase (ALOX15) in human pathologies.Progress in lipid research · 2019Review
- Soluble epoxide hydrolase inhibitor promotes immunomodulation to inhibit bone resorption.Journal of periodontal research · 2018Article
- Physiological Consequences of Coronary Arteriolar Dysfunction and Its Influence on Cardiovascular Disease.Physiology (Bethesda, Md.) · 2018Review
- GPR40 is a low-affinity epoxyeicosatrienoic acid receptor in vascular cells.The Journal of biological chemistry · 2018Article
- Role of oxylipins in cardiovascular diseases.Acta pharmacologica Sinica · 2018Review
31 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Epoxyeicosatrienoic acids (EETs) are metabolized by soluble epoxide hydrolase (sEH) to form dihydroxyeicosatrienoic acids (DHETs) and are putative endothelium-derived hyperpolarizing factors (EDHFs). EDHFs modulate microvascular tone; however, the chemical identity of EDHF in the human coronary microcirculation is not known. We examined the capacity of EETs, DHETs, and sEH inhibition to affect vasomotor tone in isolated human coronary arterioles (HCAs). HCAs from right atrial appendages were prepared for videomicroscopy and immunohistochemistry. In vessels preconstricted with endothelin-1, three EET regioisomers (8,9-, 11,12-, and 14,15-EET) each induced a concentration-dependent dilation that was sensitive to blockade of large-conductance Ca2+-activated K+ (BK(Ca)) channels by iberiotoxin. EET-induced dilation was not altered by endothelial denudation. 8,9-, 11,12-, and 14,15-DHET also dilated HCA via activation of BK(Ca) channels. Dilation was less with 8,9- and 14,15-DHET but was similar with 11,12-DHET, compared with the corresponding EETs. Immunohistochemistry revealed prominent expression of cytochrome P-450 (CYP450) 2C8, 2C9, and 2J2, enzymes that may produce EETs, as well as sEH, in HCA. Inhibition of sEH by 1-cyclohexyl-3-dodecylurea (CDU) enhanced dilation caused by 14,15-EET but reduced dilation observed with 11,12-EET. DHET production from exogenous EETs was reduced in vessels pretreated with CDU compared with control, as measured by liquid chromatography electrospray-ionization mass spectrometry. In conclusion, EETs and DHETs dilate HCA by activating BK(Ca) channels, supporting a role for EETs/DHETs as EDHFs in the human heart. CYP450s and sEH may be endogenous sources of these compounds, and sEH inhibition has the potential to alter myocardial perfusion, depending on which EETs are produced endogenously.
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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.