14,15-Epoxyeicosa-5(
            <i>Z</i>
            )-enoic Acid

Gauthier, Kathryn M.; Deeter, Christina; Krishna, U. Murali; Reddy, Y. Krishna; Bondlela, Muralidhar; Falck, John R.; Campbell, William B.

doi:10.1161/01.res.0000018162.87285.f8

Cited by 180 publications

(132 citation statements)

References 53 publications

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“…Among the four regioisomers of EETs, 14,15-EEZE-mSI appears to be more selective for 14,15-EET and 5,6-EET (Gauthier et al, 2003), whereas 14,15-EEZE inhibits relaxation to all four regioisomers (Gauthier et al, 2002).The substantial inhibition of the LDF response to whisker stimulation with 14,15-EEZE-mSI is consistent with results showing that 14,15-EET is a major regioisomer synthesized in astrocytes (Alkayed et al, 1996;Amruthesh et al, 1993) and is either metabolized by epoxide hydrolase or incorporated into the phospholipid membrane (Shivachar et al, 1995). Because of its broad spectrum potency, 14,15-EEZE, rather than 14,15-EEZE-mSI, was chosen for testing interactions with adenosine and mGluR pathways.…”

Section: Epoxyeicosatrienoic Acidsmentioning

confidence: 94%

“…Because preformed, stored EETs can be released from the phospholipid membrane (Shivachar et al, 1995), the EET antagonists 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) and 14,15-epoxyeicosa-5(Z)-enoic methylsulfonylimide (14,15-EEZE-mSI) were also used to confirm the role of EETs in this study (Gauthier et al, 2002(Gauthier et al, , 2003 and to test the interaction between EETs and adenosine pathways.…”

Section: Introductionmentioning

confidence: 99%

“…Likewise, 14,15-EEZE (30 mmol/L) reduced the response to 55720% of the baseline response, with no further change after the second hour of superfusion ( Figure 5E; n = 6). Because 14,15-EEZE can antagonize the action of all four regioisomers (Gauthier et al, 2002), this antagonist was used in further experiments.…”

mentioning

confidence: 99%

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Interaction of Mechanisms Involving Epoxyeicosatrienoic Acids, Adenosine Receptors, and Metabotropic Glutamate Receptors in Neurovascular Coupling in Rat Whisker Barrel Cortex

Shi

Liu

Gebremedhin

et al. 2007

J Cereb Blood Flow Metab

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Adenosine, astrocyte metabotropic glutamate receptors (mGluRs), and epoxyeicosatrienoic acids (EETs) have been implicated in neurovascular coupling. Although A 2A and A 2B receptors mediate cerebral vasodilation to adenosine, the role of each receptor in the cerebral blood flow (CBF) response to neural activation remains to be fully elucidated. In addition, adenosine can amplify astrocyte calcium, which may increase arachidonic acid metabolites such as EETs. The interaction of these pathways was investigated by determining if combined treatment with antagonists exerted an additive inhibitory effect on the CBF response. During whisker stimulation of anesthetized rats, the increase in cortical CBF was reduced by approximately half after individual administration of A 2B , mGluR and EET antagonists and EET synthesis inhibitors. Combining treatment of either a mGluR antagonist, an EET antagonist, or an EET synthesis inhibitor with an A 2B receptor antagonist did not produce an additional decrement in the CBF response. Likewise, the CBF response also remained reduced by B50% when an EET antagonist was combined with an mGluR antagonist or an mGluR antagonist plus an A 2B receptor antagonist. In contrast, A 2A and A 3 receptor antagonists had no effect on the CBF response to whisker stimulation. We conclude that (1) adenosine A 2B receptors, rather than A 2A or A 3 receptors, play a significant role in coupling cortical CBF to neuronal activity, and (2) the adenosine A 2B receptor, mGluR, and EETs signaling pathways are not functionally additive, consistent with the possibility of astrocytic mGluR and adenosine A 2B receptor linkage to the synthesis and release of vasodilatory EETs.

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Section: Epoxyeicosatrienoic Acidsmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Interaction of Mechanisms Involving Epoxyeicosatrienoic Acids, Adenosine Receptors, and Metabotropic Glutamate Receptors in Neurovascular Coupling in Rat Whisker Barrel Cortex

Shi

Liu

Gebremedhin

et al. 2007

J Cereb Blood Flow Metab

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“…The endothelium functions as a major vascular control mechanism by releasing vasodilator substances such as nitric oxide (NO), prostacyclin (PGI 2 ) and endothelium-derived hyperpolarizing factors (EDHFs) [1][2][3]. A decrease in endothelium-derived vasodilators impairs vascular relaxation and thereby contributes to the increased vascular resistance and blood pressure in hypertension.…”

Section: Introductionmentioning

confidence: 99%

The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

Hynynen

Khalil²

2006

PRC

107

105

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The discovery of endothelin two decades ago has now evolved into an intricate vascular endothelin (ET) system. Several ET isoforms, receptors, signaling pathways, agonists, antagonists, and clinical applications have been identified and documented in first-rate patents. The role of ET as one of the most potent endothelium-derived vasoconstricting factors is now complemented by a newly discovered role in vascular relaxation. ET synthesis is initiated by the transcription of ET genes in endothelial cells and the generation of the gene products preproET and big ET, which are further cleaved by specific ET converting enzymes into ET-1, -2, -3 and -4 isoforms. ET isoforms bind with different affinities to ET A and ET B2 receptors in vascular smooth muscle, and stimulate [Ca 2+ ] i , protein kinase C, mitogen-activated protein kinase and other signaling mechanisms of smooth muscle contraction, growth and proliferation. ET also binds to endothelial ET B1 receptors, which mediate the release of vasodilator substances such as nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor. Endothelial ET B1 receptors may also function in ET re-uptake and clearance. Although the effects of ET on vascular function and growth are well-recognized, the role of ET and its receptors in the regulation of blood pressure and in the pathogenesis of hypertension is not clearly established. Salt-dependent hypertension in experimental animals and some forms of moderate to severe hypertension in human may show elevated levels of plasma or vascular ET; however, other forms of hypertension show normal ET levels. The currently available ET receptor antagonists reduce blood pressure in some forms of experimental hypertension. Careful examination of recent patents may identify more effective and specific modulators of the vascular ET system for clinical use in human hypertension.

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“…Although the chemical identity of EDHF remains controversial, a large body of evidence now implicates epoxyeicosatrienoic acids (EETs), a class of AA metabolites distinct from prostaglandins [18][19][20][21][22]. In addition to serving as a compensatory dilator mechanism when NO bio-availability is reduced, EETs may represent an endogenous protective mechanism from atherosclerosis that could be targeted clinically.…”

Section: Introductionmentioning

confidence: 99%

Emerging role of epoxyeicosatrienoic acids in coronary vascular function

Larsen

Gutterman

Hatoum

2006

Eur J Clin Investigation

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The importance of endothelium-derived nitric oxide in coronary vascular regulation is well-established and the loss of this vasodilator compound is associated with endothelial dysfunction, tissue hypoperfusion and atherosclerosis. Numerous studies indicate that the endothelium produces another class of compounds, the epoxyeicosatrienoic acids (EETs), which may partially compensate for the loss of nitric oxide in cardiovascular disease. The EETs are endogenous lipids which are derived through the metabolism of arachidonic acid by cytochrome P450 epoxygenase enzymes. Also, EETs hyperpolarize vascular smooth muscle and induce dilation of coronary arteries and arterioles, and therefore may be endogenous mediators of coronary vasomotor tone and myocardial perfusion. In addition, EETs have been shown to inhibit vascular smooth muscle migration, decrease inflammation, inhibit platelet aggregation and decrease adhesion molecule expression, therefore representing an endogenous protective mechanism against atherosclerosis. Endogenous EETs are degraded to less active dihydroxyeicosatrienoic acids by soluble epoxide hydrolase. Pharmacological inhibition of soluble epoxide hydrolase has received considerable attention as a potential approach to enhance EET-mediated vascular protection, and several compounds have appeared promising in recent animal studies. The present review discusses the emerging role of EETs in coronary vascular function, as well as recent advancements in the development of pharmacological agents to enhance EET bioavailability.

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14,15-Epoxyeicosa-5( Z )-enoic Acid

Cited by 180 publications

References 53 publications

Interaction of Mechanisms Involving Epoxyeicosatrienoic Acids, Adenosine Receptors, and Metabotropic Glutamate Receptors in Neurovascular Coupling in Rat Whisker Barrel Cortex

Interaction of Mechanisms Involving Epoxyeicosatrienoic Acids, Adenosine Receptors, and Metabotropic Glutamate Receptors in Neurovascular Coupling in Rat Whisker Barrel Cortex

The Vascular Endothelin System in Hypertension - Recent Patents and Discoveries

Emerging role of epoxyeicosatrienoic acids in coronary vascular function

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