ArticleAmerican journal of physiology. Heart and circulatory physiology2011
Increases in plasma trans-EETs and blood pressure reduction in spontaneously hypertensive rats.
Article in American journal of physiology. Heart and circulatory physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Hemodialysis and erythrocyte epoxy fatty acids.Physiological reports · 2020Trial
- Cytochrome P450-derived Epoxyeicosatrienoic Acid, the Regulation of Cardiovascular-related Diseases, and the Implication for Pulmonary Hypertension.Cardiovascular drugs and therapy · 2025Review
- Regulation of P450-derived epoxy fatty acids in cardiovascular diseases.Redox biochemistry and chemistry · 2025Article
- Frequency of Gene Polymorphisms in Admixed Venezuelan Women with Recurrent Pregnancy Loss: Microsomal Epoxy Hydroxylase (rs1051740) and Enos (rs1799983).Current issues in molecular biology · 2024Article
- The involvement of soluble epoxide hydrolase in the development of cardiovascular diseases through epoxyeicosatrienoic acids.Frontiers in pharmacology · 2024Review
- Hemodialysis and Plasma Oxylipin Biotransformation in Peripheral Tissue.Metabolites · 2022Article
- Monolayer autoxidation of arachidonic acid to epoxyeicosatrienoic acids as a model of their potential formation in cell membranes.Journal of lipid research · 2022Article
- Early Renal Vasodilator and Hypotensive Action of Epoxyeicosatrienoic Acid Analog (EET-A) and 20-HETE Receptor Blocker (AAA) in Spontaneously Hypertensive Rats.Frontiers in physiology · 2021Article
- Changes in erythrocyte membrane epoxyeicosatrienoic, dihydroxyeicosatrienoic, and hydroxyeicosatetraenoic acids during pregnancy.Life sciences · 2021Article
- Association between CYP2C19 gene polymorphisms and lipid metabolism in Chinese patients with ischemic stroke.The Journal of international medical research · 2020Article
- Effects of hemodialysis on plasma oxylipins.Physiological reports · 2020Article
- Maximal exercise and erythrocyte epoxy fatty acids: a lipidomics study.Physiological reports · 2019Article
- Maximal exercise and plasma cytochrome P450 and lipoxygenase mediators: a lipidomics study.Physiological reports · 2019Article
- Increased arterial pressure in mice with overexpression of the ADHD candidate gene calcyon in forebrain.PloS one · 2019Article
- GPR40 is a low-affinity epoxyeicosatrienoic acid receptor in vascular cells.The Journal of biological chemistry · 2018Article
- Liraglutide protects cardiac function in diabetic rats through the PPARα pathway.Bioscience reports · 2018Article
- Enzymatic and free radical formation of cis- and trans- epoxyeicosatrienoic acids in vitro and in vivo.Free radical biology & medicine · 2017Article
- 11,12-Epoxyecosatrienoic acids mitigate endothelial dysfunction associated with estrogen loss and aging: Role of membrane depolarization.Journal of molecular and cellular cardiology · 2016Article
- Omeprazole increases the efficacy of a soluble epoxide hydrolase inhibitor in a PGE₂ induced pain model.Toxicology and applied pharmacology · 2015Article
- Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Epoxyeicosatrienoic acids (EETs) are vasodilator, natriuretic, and antiinflammatory lipid mediators. Both cis- and trans-EETs are stored in phospholipids and in red blood cells (RBCs) in the circulation; the maximal velocity (V(max)) of trans-EET hydrolysis by soluble epoxide hydrolase (sEH) is threefold that of cis-EETs. Because RBCs of the spontaneously hypertensive rat (SHR) exhibit increased sEH activity, a deficiency of trans-EETs in the SHR was hypothesized to increase blood pressure (BP). This prediction was fulfilled, since sEH inhibition with cis-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid (AUCB; 2 mg·kg(-1)·day(-1) for 7 days) in the SHR reduced mean BP from 176 ± 8 to 153 ± 5 mmHg (P < 0.05), whereas BP in the control Wistar-Kyoto rat (WKY) was unaffected. Plasma levels of EETs in the SHR were lower than in the age-matched control WKY (16.4 ± 1.6 vs. 26.1 ± 1.8 ng/ml; P < 0.05). The decrease in BP in the SHR treated with AUCB was associated with an increase in plasma EETs, which was mostly accounted for by increasing trans-EET from 4.1 ± 0.2 to 7.9 ± 1.5 ng/ml (P < 0.05). Consistent with the effect of increased plasma trans-EETs and reduced BP in the SHR, the 14,15-trans-EET was more potent (ED(50) 10(-10) M; maximum dilation 59 ± 15 μm) than the cis-isomer (ED(50) 10(-9) M; maximum dilation 30 ± 11 μm) in relaxing rat preconstricted arcuate arteries. The 11,12-EET cis- and trans-isomers were equipotent dilators as were the 8,9-EET isomers. In summary, inhibition of sEH resulted in a twofold increase in plasma trans-EETs and reduced mean BP in the SHR. The greater vasodilator potency of trans- vs. cis-EETs may contribute to the antihypertensive effects of sEH inhibitors.
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