Identification of epoxyeicosatrienoic acids as endothelium-derived hyperpolarizing factors.

Abstract:

:Endothelial cells release several compounds, including prostacyclin, NO, and endothelium-derived hyperpolarizing factor (EDHF), that mediate the vascular effects of vasoactive hormones. The identity of EDHF remains unknown. Since arachidonic acid causes endothelium-dependent relaxations of coronary arteries through its metabolism to epoxyeicosatrienoic acids (EETs) by cytochrome P450, we wondered if the EETs represent EDHFs. Precontracted bovine coronary arteries relaxed in an endothelium-dependent manner to methacholine. The cytochrome P450 inhibitors, SKF 525A and miconazole, significantly attenuated these relaxations. They were also inhibited by tetraethylammonium (TEA),an inhibitor of Ca2+-activated K+ channels, and by high [K+]0 (20 mmol/L). Methacholine also caused hyperpolarization of coronary smooth muscle (-27 +/- 3.9 versus -40 +/- 5.1 mV), which was completely blocked by SKF 525A and miconazole. In vessels prelabeled with [3H] arachidonic acid, methacholine stimulated the release of 6-ketoprostaglandin F1alpha, 12-HETE, and the EETs. Arachidonic acid relaxed precontracted coronary arteries, which were also blocked by TEA, charybdotoxin, another Ca2+-activated K+ channel inhibitor, and high [K+]0. 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET relaxed precontracted coronary vessels (EC50, 1 X 10(-6) mol/L). The four regioisomers were equally active. TEA, charybdotoxin, and high [K+]0 attenuated the EET relaxations. 11,12-EET hyperpolarized coronary smooth muscle cells from -37 +/- 0.2 to -59 +/- 0.3 mV. In the cell-attached mode of patch clamp, both 14,15-EET and 11,12-EET increased the open-state probability of a Ca2+-activated K+ channel in coronary smooth muscle cells. This effect was blocked by TEA and charybdotoxin. These data support the hypothesis that the EETs are EDHFs.

journal_name

Circ Res

journal_title

Circulation research

authors

Campbell WB,Gebremedhin D,Pratt PF,Harder DR

doi

10.1161/01.res.78.3.415

subject

Has Abstract

pub_date

1996-03-01 00:00:00

pages

415-23

issue

3

eissn

0009-7330

issn

1524-4571

journal_volume

78

pub_type

杂志文章
  • miR33 inhibition overcomes deleterious effects of diabetes mellitus on atherosclerosis plaque regression in mice.

    abstract:RATIONALE:Diabetes mellitus increases cardiovascular disease risk in humans and remains elevated despite cholesterol-lowering therapy with statins. Consistent with this, in mouse models, diabetes mellitus impairs atherosclerosis plaque regression after aggressive cholesterol lowering. MicroRNA 33 (miR33) is a key negat...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.115.304164

    authors: Distel E,Barrett TJ,Chung K,Girgis NM,Parathath S,Essau CC,Murphy AJ,Moore KJ,Fisher EA

    更新日期:2014-10-10 00:00:00

  • Hypoxia stimulates prostacyclin synthesis in newborn pulmonary artery endothelium by increasing cyclooxygenase-1 protein.

    abstract::In newborn lambs, pulmonary prostacyclin (PGI2) production increases acutely in response to low oxygen. We tested the hypothesis that decreased oxygenation directly stimulates PGI2 synthesis in arterial segments and cultured endothelial cells from newborn lamb intrapulmonary arteries. In segments studied at PO2 of 680...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.75.1.33

    authors: North AJ,Brannon TS,Wells LB,Campbell WB,Shaul PW

    更新日期:1994-07-01 00:00:00

  • MicroRNA-103/107 Regulate Programmed Necrosis and Myocardial Ischemia/Reperfusion Injury Through Targeting FADD.

    abstract:RATIONALE:Necrosis is one of the main forms of cardiomyocyte death in heart disease. Recent studies have demonstrated that certain types of necrosis are regulated and programmed dependent on the activation of receptor-interacting serine/threonine-protein kinase (RIPK) 1 and 3 which may be negatively regulated by Fas-as...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.117.305781

    authors: Wang JX,Zhang XJ,Li Q,Wang K,Wang Y,Jiao JQ,Feng C,Teng S,Zhou LY,Gong Y,Zhou ZX,Liu J,Wang JL,Li PF

    更新日期:2015-07-31 00:00:00

  • Spatiotemporal heterogeneity in the induction of ventricular fibrillation by rapid pacing: importance of cardiac restitution properties.

    abstract::The mechanism by which rapid pacing induces ventricular fibrillation (VF) is unclear. We performed computerized epicardial mapping studies in 10 dogs, using 19-beat pacing trains. The pacing interval (PI) of the first train was 300 ms and then was progressively shortened until VF was induced. For each PI, we construct...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.84.11.1318

    authors: Cao JM,Qu Z,Kim YH,Wu TJ,Garfinkel A,Weiss JN,Karagueuzian HS,Chen PS

    更新日期:1999-06-11 00:00:00

  • Important role of erythropoietin receptor to promote VEGF expression and angiogenesis in peripheral ischemia in mice.

    abstract::We have recently demonstrated that endogenous erythropoietin (Epo)/Epo receptor (EpoR) system plays an important protective role in hypoxia-induced pulmonary hypertension. However, it remains to be examined whether vascular EpoR system contributes to angiogenesis in response to ischemia. We examined angiogenesis in Ep...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000260179.43672.fe

    authors: Nakano M,Satoh K,Fukumoto Y,Ito Y,Kagaya Y,Ishii N,Sugamura K,Shimokawa H

    更新日期:2007-03-16 00:00:00

  • Allograft vasculopathy versus atherosclerosis.

    abstract::Over the last 4 decades, heart transplantation (HTx) has evolved as a mainstream therapy for heart failure. Approximately half of patients needing HTx have organ failure consequent to atherosclerosis. Despite advances in immunosuppressive drugs, long-term success of HTx is limited by the development of a particular ty...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.RES.0000246086.93555.f3

    authors: Rahmani M,Cruz RP,Granville DJ,McManus BM

    更新日期:2006-10-13 00:00:00

  • The art of microRNA research.

    abstract::Originally identified as moderate biological modifiers, microRNAs have recently emerged as powerful regulators of diverse cellular processes with especially important roles in disease and tissue remodeling. The rapid pace of studies on microRNA regulation and function necessitates the development of suitable technique...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.110.227496

    authors: van Rooij E

    更新日期:2011-01-21 00:00:00

  • Mechanistic insights into nitrite-induced cardioprotection using an integrated metabolomic/proteomic approach.

    abstract::Nitrite has recently emerged as an important bioactive molecule, capable of conferring cardioprotection and a variety of other benefits in the cardiovascular system and elsewhere. The mechanisms by which it accomplishes these functions remain largely unclear. To characterize the dose response and corresponding cardiac...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.108.187005

    authors: Perlman DH,Bauer SM,Ashrafian H,Bryan NS,Garcia-Saura MF,Lim CC,Fernandez BO,Infusini G,McComb ME,Costello CE,Feelisch M

    更新日期:2009-03-27 00:00:00

  • Partial purification of human renin.

    abstract::An affinity gel for the purification of renin was prepared by coupling pepstatin to aminohexylagarose gel. Partially purified human renin (Haas et al., Arch. Biochem. Biophys., 110, 534-543, 1965) was purified further by affinity chromatography on the pepstatin-aminohexyl-agarose gel, gel filtration on a Sephadex G-75...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.41.4.4

    authors: Murakami K,Inagami T,Haas E

    更新日期:1977-10-01 00:00:00

  • Cardiotrophic effects of protein kinase C epsilon: analysis by in vivo modulation of PKCepsilon translocation.

    abstract::Protein kinase C (PKC) is a key mediator of many diverse physiological and pathological responses. Although little is known about the specific in vivo roles of the various cardiac PKC isozymes, activation-induced translocation of PKC is believed to be the primary determinant of isozyme-specific functions. Recently, we...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.86.11.1173

    authors: Mochly-Rosen D,Wu G,Hahn H,Osinska H,Liron T,Lorenz JN,Yatani A,Robbins J,Dorn GW 2nd

    更新日期:2000-06-09 00:00:00

  • Role of vascular cell adhesion molecule-1 and fibronectin connecting segment-1 in monocyte rolling and adhesion on early atherosclerotic lesions.

    abstract::Atherosclerotic lesion development seems to be inflammatory in nature and involves the recruitment of monocytes to the vessel wall. In this study, we investigated the role of vascular cell adhesion molecule-1 (VCAM-1) and fibronectin (FN) connecting segment-1 containing the amino acid sequence ILDV as functional ligan...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.87.2.153

    authors: Huo Y,Hafezi-Moghadam A,Ley K

    更新日期:2000-07-21 00:00:00

  • Haplotypes of the caspase-1 gene, plasma caspase-1 levels, and cardiovascular risk.

    abstract::Caspase-1 processes the interleukin (IL)-1beta and IL-18 inactive precursors to the biologically active cytokines that are known to have proatherogenic effects. The present study investigated the genetic variability of the CASP1 gene and plasma levels of caspase-1 in relation to cardiovascular risk. In Europeans, 3 ta...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000232324.87983.4b

    authors: Blankenberg S,Godefroy T,Poirier O,Rupprecht HJ,Barbaux S,Bickel C,Nicaud V,Schnabel R,Kee F,Morrison C,Evans A,Lackner KJ,Cambien F,Münzel T,Tiret L,AtheroGene Investigators.

    更新日期:2006-07-07 00:00:00

  • Importance of endogenous angiotensin II in the cardiovascular responses to sympathetic stimulation in conscious rabbits.

    abstract::Pharmacological evidence indicates that angiotensin (Ang II) converting enzyme inhibitors attenuate cardiovascular responses to sympathetic stimulation. To investigate the physiological significance of this attenuation, the pressor and heart rate responses to bilateral carotid occlusion (BCO) were studied before and a...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.66.3.662

    authors: Isaacson JS,Reid IA

    更新日期:1990-03-01 00:00:00

  • Genetic Deficiency of Glutathione S-Transferase P Increases Myocardial Sensitivity to Ischemia-Reperfusion Injury.

    abstract:RATIONALE:Myocardial ischemia-reperfusion (I/R) results in the generation of oxygen-derived free radicals and the accumulation of lipid peroxidation-derived unsaturated aldehydes. However, the contribution of aldehydes to myocardial I/R injury has not been assessed. OBJECTIVE:We tested the hypothesis that removal of a...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.114.305518

    authors: Conklin DJ,Guo Y,Jagatheesan G,Kilfoil PJ,Haberzettl P,Hill BG,Baba SP,Guo L,Wetzelberger K,Obal D,Rokosh DG,Prough RA,Prabhu SD,Velayutham M,Zweier JL,Hoetker JD,Riggs DW,Srivastava S,Bolli R,Bhatnagar A

    更新日期:2015-08-14 00:00:00

  • Hemodynamic effects of diltiazem in hypertension.

    abstract::Cardiac hemodynamics, diameter, blood flow velocity, and volumic flow of the brachial artery were studied before and after diltiazem administration in 11 patients with sustained essential hypertension. The study was compared with the hemodynamic effects of dihydralazine. The caliber of the brachial artery was evaluate...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:

    authors: Safar ME,Simon AC,Levenson JA,Cazor JL

    更新日期:1983-02-01 00:00:00

  • Skinned fibers of human atrium and ventricle: myosin isoenzymes and contractility.

    abstract::Different myosin isoenzymes of pig and human atrium and ventricle and rat ventricle were characterized by two approaches: pyrophosphate polyacrylamide gel electrophoresis (PP-PAGE) and analysis of the myosin P light chains by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). We further investigated the rel...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.62.3.632

    authors: Morano I,Arndt H,Gärtner C,Rüegg JC

    更新日期:1988-03-01 00:00:00

  • Nitric oxide/cAMP interactions in the control of rat renal vascular resistance.

    abstract::This study aimed to characterize the interaction between nitric oxide (NO)- and cAMP-related pathways in the control of renal blood flow. Using the isolated perfused rat kidney model, we determined the effects of inhibition of NO formation by Nomega-nitro-L-arginine methyl ester (L-NAME; 1 mmol/L) and of NO administra...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.84.2.186

    authors: Sandner P,Kornfeld M,Ruan X,Arendshorst WJ,Kurtz A

    更新日期:1999-02-05 00:00:00

  • Adenosine 3',5'-cyclic-monophosphate-dependent regulation of alpha 1-adrenergic receptor number in rabbit aortic smooth muscle cells.

    abstract::The purpose of this study was to determine whether a cyclic adenosine 3',5'-monophosphate-dependent process can be involved in the regulation of vascular smooth muscle alpha 1-adrenergic receptor responsiveness. Experiments were performed in cultured rabbit aortic smooth muscle cells which were characterized previousl...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.58.2.292

    authors: Colucci WS

    更新日期:1986-02-01 00:00:00

  • Reduced myocardial reflow and increased coronary vascular resistance following prolonged myocardial ischemia in the dog.

    abstract::Studies were performed to determine whether an alteration in coronary vascular resistance and a reduction in the reflow phenomenon occurred in the blood-perfused, heparinized canine heart after various periods of myocaridal ischemia. Regional myocardial blood flow was measured with radioactive microspheres. Proximal l...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.36.6.771

    authors: Willerson JT,Watson JT,Hutton I,Templeton GH,Fixler DE

    更新日期:1975-06-01 00:00:00

  • Hypercholesterolemia suppresses inwardly rectifying K+ channels in aortic endothelium in vitro and in vivo.

    abstract::Inwardly rectifying K+ (Kir) channels are responsible for maintaining endothelial membrane potential and play a key role in endothelium-dependent vasorelaxation. In this study, we show that endothelial Kir channels are suppressed by hypercholesterolemic levels of lipoproteins in vitro and by serum hypercholesterolemia...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000218776.87842.43

    authors: Fang Y,Mohler ER 3rd,Hsieh E,Osman H,Hashemi SM,Davies PF,Rothblat GH,Wilensky RL,Levitan I

    更新日期:2006-04-28 00:00:00

  • Changes in extracellular potassium activity in response to decreased pH in rabbit atrial muscle.

    abstract::The extracellular and intracellular potassium (K+) activities of isolated superfused rabbit atrial muscle were measured using K+-sensitive liquid ion exchanger microelectrodes. When the pH of the bathing medium was decreased from 7.5 to 6.8, intracellular K+ activity fell and extracellular K+ activity rose from a mean...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.39.5.678

    authors: Skinner RB Jr,Kunze DL

    更新日期:1976-11-01 00:00:00

  • Left ventricular myocardial edema. Lymph flow, interstitial fibrosis, and cardiac function.

    abstract::We hypothesized that both acute and chronic accumulation of myocardial interstitial edema (extravascular fluid [EVF]) would compromise cardiac function. We also postulated that excess fluid within the myocardial interstitial space would potentiate interstitial fibrosis, thus further compromising function. Dogs were di...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.6.1713

    authors: Laine GA,Allen SJ

    更新日期:1991-06-01 00:00:00

  • Bone marrow monocyte lineage cells adhere on injured endothelium in a monocyte chemoattractant protein-1-dependent manner and accelerate reendothelialization as endothelial progenitor cells.

    abstract::Peripheral blood (PB)-derived CD14+ monocytes were shown to transdifferentiate into endothelial cell (EC) lineage cells and contribute to neovascularization. We investigated whether bone marrow (BM)- or PB-derived CD34-/CD14+ cells are involved in reendothelialization after carotid balloon injury. Although neither hem...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000099245.08637.CE

    authors: Fujiyama S,Amano K,Uehira K,Yoshida M,Nishiwaki Y,Nozawa Y,Jin D,Takai S,Miyazaki M,Egashira K,Imada T,Iwasaka T,Matsubara H

    更新日期:2003-11-14 00:00:00

  • Voltage- and use-dependent effects of lidocaine on sodium current in rat single ventricular cells.

    abstract::We compared the blocking effects of the local anesthetics, lidocaine and benzocaine, on the sodium current, using single rat ventricular cells to obtain further information about the voltage dependence and kinetics of local anesthetic interaction with cardiac sodium channels. We used a hybrid voltage clamp system whic...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.52.5.557

    authors: Sanchez-Chapula J,Tsuda Y,Josephson IR

    更新日期:1983-05-01 00:00:00

  • Diabetes-induced alterations in atrial natriuretic peptide gene expression in Wistar-Kyoto and spontaneously hypertensive rats.

    abstract::We investigated the effects of streptozotocin-induced diabetes on atrial natriuretic peptide (ANP) synthesis, hemodynamic parameters, blood volume, and histopathology, as well as the reversibility of such effects with insulin therapy in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). The biatrial A...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.67.4.803

    authors: Matsubara H,Mori Y,Yamamoto J,Inada M

    更新日期:1990-10-01 00:00:00

  • Increased Epicardial Adipose Tissue Volume Correlates With Cardiac Sympathetic Denervation in Patients With Heart Failure.

    abstract:RATIONALE:It has been reported that epicardial adipose tissue (EAT) may affect myocardial autonomic function. OBJECTIVE:The aim of this study was to explore the relationship between EAT and cardiac sympathetic nerve activity in patients with heart failure. METHODS AND RESULTS:In 110 patients with systolic heart failu...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.115.307765

    authors: Parisi V,Rengo G,Perrone-Filardi P,Pagano G,Femminella GD,Paolillo S,Petraglia L,Gambino G,Caruso A,Grimaldi MG,Baldascino F,Nolano M,Elia A,Cannavo A,De Bellis A,Coscioni E,Pellegrino T,Cuocolo A,Ferrara N,Leosco D

    更新日期:2016-04-15 00:00:00

  • Branching patterns in the porcine coronary arterial tree. Estimation of flow heterogeneity.

    abstract::The aim of this study is to quantify the porcine coronary arterial branching pattern and to use this quantification for the interpretation of flow heterogeneity. Two casts of the coronary arterial tree were made at diastolic arrest and maximal dilation. The relation between length and diameter of arterial segments was...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.71.5.1200

    authors: VanBavel E,Spaan JA

    更新日期:1992-11-01 00:00:00

  • The long noncoding RNA CHRF regulates cardiac hypertrophy by targeting miR-489.

    abstract:RATIONALE:Sustained cardiac hypertrophy is often accompanied by maladaptive cardiac remodeling leading to decreased compliance and increased risk for heart failure. Maladaptive hypertrophy is considered to be a therapeutic target for heart failure. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have various biolo...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.114.302476

    authors: Wang K,Liu F,Zhou LY,Long B,Yuan SM,Wang Y,Liu CY,Sun T,Zhang XJ,Li PF

    更新日期:2014-04-25 00:00:00

  • The dystrophin glycoprotein complex: signaling strength and integrity for the sarcolemma.

    abstract::The dystrophin glycoprotein complex (DGC) is a specialization of cardiac and skeletal muscle membrane. This large multicomponent complex has both mechanical stabilizing and signaling roles in mediating interactions between the cytoskeleton, membrane, and extracellular matrix. Dystrophin, the protein product of the Duc...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.RES.0000126574.61061.25

    authors: Lapidos KA,Kakkar R,McNally EM

    更新日期:2004-04-30 00:00:00

  • S100A8 and S100A9 mediate endotoxin-induced cardiomyocyte dysfunction via the receptor for advanced glycation end products.

    abstract::Cardiovascular dysfunction as a result of sepsis is the leading cause of death in the critically ill. Cardiomyocytes respond to infectious pathogens with a Toll-like receptor-initiated proinflammatory response in conjunction with a decrease in contractility, although the downstream events linking Toll-like receptor ac...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.107.167544

    authors: Boyd JH,Kan B,Roberts H,Wang Y,Walley KR

    更新日期:2008-05-23 00:00:00