ArticleToxicology and applied pharmacology2012
Elevated blood pressure in cytochrome P4501A1 knockout mice is associated with reduced vasodilation to omega-3 polyunsaturated fatty acids.
Article in Toxicology and applied pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 52 citations in OpenAlex.
- Comparison of the effects of long-chain omega-3 fatty acid supplementation on plasma levels of free and esterified oxylipins.Prostaglandins & other lipid mediators · 2014Trial
- Increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acid levels in human plasma after a single dose of long-chain omega-3 PUFA.Prostaglandins & other lipid mediators · 2014Trial
- Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway.Journal of lipid research · 2014Trial
- Modulation of blood oxylipin levels by long-chain omega-3 fatty acid supplementation in hyper- and normolipidemic men.Prostaglandins, leukotrienes, and essential fatty acidsTrial
- The Expression of GenesBiomedicines · 2024Article
- Oxylipins as Biomarkers for Aromatase Inhibitor-Induced Arthralgia (AIA) in Breast Cancer Patients.Metabolites · 2023Article
- Review
- Structure-based virtual screening of CYP1A1 inhibitors: towards rapid tier-one assessment of potential developmental toxicants.Archives of toxicology · 2021Article
- Possible Role of CYP450 Generated Omega-3/Omega-6 PUFA Metabolites in the Modulation of Blood Pressure and Vascular Function in Obese Children.Nutrients · 2018Article
- Mechanisms of BK Channel Activation by Docosahexaenoic Acid in Rat Coronary Arterial Smooth Muscle Cells.Frontiers in pharmacology · 2018Article
- Omega-3 Polyunsaturated Fatty Acids Protect Against Cigarette Smoke-Induced Oxidative Stress and Vascular Dysfunction.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Genetic dissection of endothelial transcriptional activity of zebrafish aryl hydrocarbon receptors (AHRs).PloS one · 2017Article
- The gene-expression profile of renal medulla in ISIAH rats with inherited stress-induced arterial hypertension.BMC genetics · 2016Article
- Overview of Antagonists Used for Determining the Mechanisms of Action Employed by Potential Vasodilators with Their Suggested Signaling Pathways.Molecules (Basel, Switzerland) · 2016Review
- Comparative transcriptional profiling of renal cortex in rats with inherited stress-induced arterial hypertension and normotensive Wistar Albino Glaxo rats.BMC genetics · 2016Article
- Chronic Nicotine Exposure Abolishes Maternal Systemic and Renal Adaptations to Pregnancy in Rats.PloS one · 2016Article
- Regulation of Human Cytochrome P4501A1 (hCYP1A1): A Plausible Target for Chemoprevention?BioMed research international · 2016Review
- Role of CYP eicosanoids in the regulation of pharyngeal pumping and food uptake in Caenorhabditis elegans.Journal of lipid research · 2015Article
- Role of CYP1A1 in modulating the vascular and blood pressure benefits of omega-3 polyunsaturated fatty acids.The Journal of pharmacology and experimental therapeutics · 2014Article
- ω-3 polyunsaturated fatty acids-derived lipid metabolites on angiogenesis, inflammation and cancer.Prostaglandins & other lipid mediators · 2014Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In vitro cytochrome P4501A1 (CYP1A1) metabolizes omega-3 polyunsaturated fatty acids (n-3 PUFAs); eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), primarily to 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP), respectively. These metabolites have been shown to mediate vasodilation via increases in nitric oxide (NO) and activation of potassium channels. We hypothesized that genetic deletion of CYP1A1 would reduce vasodilatory responses to n-3 PUFAs, but not the metabolites, and increase blood pressure (BP) due to decreases in NO. We assessed BP by radiotelemetry in CYP1A1 wildtype (WT) and knockout (KO) mice±NO synthase (NOS) inhibitor. We also assessed vasodilation to acetylcholine (ACh), EPA, DHA, 17,18-EEQ and 19,20-EDP in aorta and mesenteric arterioles. Further, we assessed vasodilation to an NO donor and to DHA±inhibitors of potassium channels. CYP1A1 KO mice were hypertensive, compared to WT, (mean BP in mmHg, WT 103±1, KO 116±1, n=5/genotype, p<0.05), and exhibited a reduced heart rate (beats per minute, WT 575±5; KO 530±7; p<0.05). However, BP responses to NOS inhibition and vasorelaxation responses to ACh and an NO donor were normal in CYP1A1 KO mice, suggesting that NO bioavailability was not reduced. In contrast, CYP1A1 KO mice exhibited significantly attenuated vasorelaxation responses to EPA and DHA in both the aorta and mesenteric arterioles, but normal vasorelaxation responses to the CYP1A1 metabolites, 17,18-EEQ and 19,20-EDP, and normal responses to potassium channel inhibition. Taken together these data suggest that CYP1A1 metabolizes n-3 PUFAs to vasodilators in vivo and the loss of these vasodilators may lead to increases in BP.
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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.