ArticleCirculation research2004
Estrogen elicits cytochrome P450--mediated flow-induced dilation of arterioles in NO deficiency: role of PI3K-Akt phosphorylation in genomic regulation.
Article in Circulation research, 2004. 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, 53 citations in OpenAlex.
- Endothelial function and insulin sensitivity during acute non-esterified fatty acid elevation: Effects of fat composition and gender.Nutrition, metabolism, and cardiovascular diseases : NMCD · 2015Trial
- Glu298Asp polymorphism influences the beneficial effects of fish oil fatty acids on postprandial vascular function.Journal of lipid research · 2012Trial
- Epoxyeicosatrienoic acids (EETs): A novel class of second messengers of hormonal functional responses.Prostaglandins & other lipid mediators · 2025Review
- Single Nucleotide Polymorphisms in Coronary Microvascular Dysfunction.Journal of the American Heart Association · 2024Review
- Roles of Genetic Predisposition in the Sex Bias of Pulmonary Pathophysiology, as a Function of Estrogens : Sex Matters in the Prevalence of Lung Diseases.Advances in experimental medicine and biology · 2021Article
- Estrogen-related mechanisms in sex differences of hypertension and target organ damage.Biology of sex differences · 2020Review
- Sexually Dimorphic Regulation of EET Synthesis and Metabolism: Roles of Estrogen.Frontiers in pharmacology · 2018Article
- Estrogen receptor α activation enhances its cell surface localization and improves myocardial redox status in ovariectomized rats.Life sciences · 2017Article
- Roles of NADPH oxidase and mitochondria in flow-induced vasodilation of human adipose arterioles: ROS-induced ROS release in coronary artery disease.Microcirculation (New York, N.Y. : 1994) · 2017Article
- EETs Elicit Direct Increases in Pulmonary Arterial Pressure in Mice.American journal of hypertension · 2016Article
- Sexually dimorphic phenotype of arteriolar responsiveness to shear stress in soluble epoxide hydrolase-knockout mice.American journal of physiology. Heart and circulatory physiology · 2015Article
- Role of aromatase in sex-specific cerebrovascular endothelial function in mice.American journal of physiology. Heart and circulatory physiology · 2014Article
- Nongenomic effects of estrogen mediate the dose-related myocardial oxidative stress and dysfunction caused by acute ethanol in female rats.American journal of physiology. Endocrinology and metabolism · 2014Article
- CYP2C29 produces superoxide in response to shear stress.Microcirculation (New York, N.Y. : 1994) · 2012Article
- A novel vascular EET synthase: role of CYP2C7.American journal of physiology. Regulatory, integrative and comparative physiology · 2011Article
- Roles of CYP2C29 and RXR gamma in vascular EET synthesis of female mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2010Article
- Estrogen replacement restores flow-induced vasodilation in coronary arterioles of aged and ovariectomized rats.American journal of physiology. Regulatory, integrative and comparative physiology · 2009Article
- Contribution of epoxyeicosatrienoic acids to flow-induced dilation in arteries of male ERalpha knockout mice: role of aromatase.American journal of physiology. Regulatory, integrative and comparative physiology · 2007Article
- COX-2 contributes to the maintenance of flow-induced dilation in arterioles of eNOS-knockout mice.American journal of physiology. Heart and circulatory physiology · 2006Article
- 17beta-Estradiol reverses shear-stress-mediated low density lipoprotein modifications.Free radical biology & medicine · 2006Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
This study investigated the mechanisms responsible for the estrogen-dependent, cytochrome P450 (CYP)-mediated dilator responses to shear stress in arterioles of NO-deficient female rats and mice. Flow-induced dilation (FID) was assessed in isolated arterioles from N(G)-nitro-L-arginine methyl ester (L-NAME)-treated male and ovariectomized female rats before and after overnight incubation with 17beta-estradiol (17beta-E2, 10(-9) mol/L). In control conditions, prostaglandins (PGs) mediated FID, because indomethacin (INDO) abolished the responses. After incubation of the vessels with 17beta-E2, the basal tone of arterioles was significantly reduced and FID was augmented. INDO did not affect the dilation of the vessels incubated with 17beta-E2. Dilations of these vessels, however, were eliminated by PPOH and miconazole, inhibitors of CYP/epoxygenase. Simultaneous incubation of the vessels with 17beta-E2 plus ICI, 182,780, an estrogen receptor antagonist, or wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K) phosphorylation or the transcriptional inhibitor DRB, prevented the reduced arteriolar tone and the enhanced CYP-mediated FID caused by incubation of vessels with 17beta-E2. Western blot analysis indicated a significantly increased phospho-Akt level in arterioles incubated with 17beta-E2 compared with those without 17beta-E2. The enhanced phospho-Akt in response to 17beta-E2 was localized, by immunohistochemistry, to arteriolar endothelial cells. Moreover, GC-MS analysis indicated a significantly increased production of epoxyeicosatrienoic acids, vasodilator metabolites of CYP/epoxygenase, in arterioles incubated with 17beta-E2, a response that was prevented by ICI 182780 and wortmannin, respectively. Thus, estrogen, via a receptor-dependent, PI3K/Akt-mediated pathway, transcriptionally upregulates CYP activity, leading to an enhanced arteriolar response to shear stress.
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