A 20-Hydroxyeicosatetraenoic Acid Agonist, N-[20-Hydroxyeicosa-5(z),14(z)-Dienoyl]glycine, Opposes the Fall in Blood Pressure and Vascular Reactivity in Endotoxin-Treated Rats

Tunçtan, Bahar; Korkmaz, Belma; Buharalioğlu, C. Kemal; Fırat, Seyhan; Anjaiah, Siddam; Falck, John R.; Roman, Richard J.; Malik, Kafait U.

doi:10.1097/shk.0b013e31816471c6

Cited by 32 publications

(38 citation statements)

References 22 publications

(38 reference statements)

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“…Mice lacking the eNOS gene displayed increased vascular 20-HETE synthesis (Huang et al, 2005). Inhibition of 20-HETE synthesis attenuated the rise in blood pressure in N -nitro-L-arginine methyl estertreated rats (Hercule et al, 2003) and induced the NO/endothelium-dependent relaxation to acetylcholine (Kerkhof et al, 1999), whereas administration of a 20-HETE agonist prevented the fall in blood pressure after endotoxin shock (Tunctan et al, 2008). In all, these studies implicate NO in the regulation of 20-HETE synthesis.…”

Section: -Hete-mediated Ikk-dependent Endothelial Dysfunction 63mentioning

confidence: 79%

20-Hydroxy-5,8,11,14-eicosatetraenoic Acid Mediates Endothelial Dysfunction via IκB Kinase-Dependent Endothelial Nitric-Oxide Synthase Uncoupling

Cheng¹,

Wu²,

Gotlinger³

et al. 2009

J Pharmacol Exp Ther

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Endothelial dysfunction and activation occur in the vasculature and are believed to contribute to the pathogenesis of cardiovascular diseases. We have shown that 8,11,, a cytochrome P450 4A-derived eicosanoid that promotes vasoconstriction in the microcirculation, uncouples endothelial nitric-oxide synthase (eNOS) and reduces nitric oxide (NO) levels via the dissociation of the 90-kDa heat shock protein (HSP90) from eNOS. It also causes endothelial activation by stimulating nuclear factor-B (NF-B) and increasing levels of proinflammatory cytokines. In this study, we examined signaling mechanisms that may link 20-HETE-induced endothelial dysfunction and activation. Under conditions in which 20-HETE inhibited NO production, it also stimulated inhibitor of NF-B (IB) phosphorylation. Both effects were prevented by inhibition of tyrosine kinases and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK). It is noteworthy that inhibitor of IB kinase (IKK) activity negated the 20-HETE-mediated inhibition of NO production. Immunoprecipitation experiments revealed that treatment of ionophore-stimulated cells with 20-HETE brings about a decrease in HSP90-eNOS association and an increase in HSP90-IKK␤ association, suggesting that the activation by 20-HETE of NF-B is linked to its action on eNOS. Furthermore, addition of inhibitors of tyrosine kinase MAPK and IKK restored the 20-HETE-mediated impairment of acetylcholine-induced relaxation in rat renal interlobar arteries. The results indicate that 20-HETE mediates eNOS uncoupling and endothelial dysfunction via the activation of tyrosine kinase, MAPK, and IKK, and these effects are linked to 20-HETE-mediated endothelial activation.The integrity of the vascular endothelium is vital to the regulation of the cardiovascular system. The endothelium serves as a protective barrier between tissues and circulating blood and functions to maintain vascular homeostasis by releasing bioactive factors in response to hemodynamic changes and blood-borne signals. An uncontrolled endothelial cell response is involved in many disease processes, including hypertension, atherosclerosis, and diabetes. These diseases are related to endothelial injury, dysfunction and activation. Nitric oxide (NO), generated from L-arginine by endothelial nitric-oxide synthase (eNOS), is a key endothelial-derived factor, the bioavailability of which is essential to the integrity and function of the endothelium. Endothelial dysfunction occurs as a result of a loss of NO bioavailability that is due to either reduced formation or accelerated degradation of NO, and it is often associated with endothelial activation. NO actively mediates many functions of the endothelium. In addition to its Article, publication date, and citation information can be found at http://jpet.aspetjournals.org. doi:10.1124/jpet.109.159863.ABBREVIATIONS: NO, nitric oxide; eNOS, endothelial nitric-oxide synthase; SMC, smooth muscle cell; 20-HETE, 20-hydroxyeicosatetraenoic acid; HSP90, 90-kDa heat shock prot...

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Section: -Hete-mediated Ikk-dependent Endothelial Dysfunction 63mentioning

confidence: 79%

20-Hydroxy-5,8,11,14-eicosatetraenoic Acid Mediates Endothelial Dysfunction via IκB Kinase-Dependent Endothelial Nitric-Oxide Synthase Uncoupling

Cheng¹,

Wu²,

Gotlinger³

et al. 2009

J Pharmacol Exp Ther

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“…H. Wang et al, 2001), (iii) vascular-selective transduction of CYP4A2 cDNA increases vascular 20-HETE synthesis and produces hypertension in SD rats (Inoue, Sodhi, et al, 2009; J. S. Wang et al, 2006), and (iv) administration of a 20-HETE analog prevents the fall in blood pressure in LPS-induced endotoxic shock in rats (Tunctan et al, 2008). Androgen-induced hypertension in male and female SD rats is 20-HETE-dependent (Nakagawa et al, 2003; Singh et al, 2007; Singh & Schwartzman, 2008).…”

Section: -Hete and Vascular Functionmentioning

confidence: 99%

20-HETE in the regulation of vascular and cardiac function

Ročić

Schwartzman

2018

Pharmacology & Therapeutics

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20-HETE, the ω-hydroxylation product of arachidonic acid catalyzed by enzymes of the cytochrome P450 (CYP) 4A and 4F gene families, is a bioactive lipid mediator with potent effects on the vasculature including stimulation of smooth muscle cell contractility, migration and proliferation as well as activation of endothelial cell dysfunction and inflammation. Clinical studies have shown elevated levels of plasma and urinary 20-HETE in human diseases and conditions such as hypertension, obesity and metabolic syndrome, myocardial infarction, stroke, and chronic kidney diseases. Studies of polymorphic associations also suggest an important role for 20-HETE in hypertension, stroke and myocardial infarction. Animal models of increased 20-HETE production are hypertensive and are more susceptible to cardiovascular injury. The current review summarizes recent findings that focus on the role of 20-HETE in the regulation of vascular and cardiac function and its contribution to the pathology of vascular and cardiac diseases.

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“…This has been the subject of several recent and definitive reviews (11, 26, 117–121). The role of 20-HETE in ischemic and hemorrhagic stroke (122–125), acute renal failure (126, 127), toxemia of pregnancy (128), hepatorenal syndrome (129), vascular restenosis (23), angiogenesis (24), cardiac hypertrophy (130) and ischemia reperfusion (IR) injury (131), as well as shock (132, 133) is less well known and has received little attention in the literature. This review will focus on the emerging pathogenic role of 20-HETE as an important mediator in vascular dysfunction, inflammation in a variety of diseases.…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms in differentiated thyroid cancer

2016

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Cytochrome P450s enzymes catalyze the metabolism of arachidonic acid to epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid and hydroxyeicosatetraeonic acid (HETEs). 20-HETE is a vasoconstrictor that depolarizes vascular smooth muscle cells by blocking K+ channels. EETs serve as endothelial derived hyperpolarizing factors. Inhibition of the formation of 20-HETE impairs the myogenic response and autoregulation of renal and cerebral blood flow. Changes in the formation of EETs and 20-HETE have been reported in hypertension and drugs that target these pathways alter blood pressure in animal models. Sequence variants in CYP4A11 and CYP4F2 that produce 20-HETE, UDP-glucuronosyl transferase involved in the biotransformation of 20-HETE and soluble epoxide hydrolase that inactivates EETs are associated with hypertension in human studies. 20-HETE contributes to the regulation of vascular hypertrophy, restenosis, angiogenesis and inflammation. It also promotes endothelial dysfunction and contributes to cerebral vasospasm and ischemia-reperfusion injury in the brain, kidney and heart. This review will focus on the role of 20-HETE in vascular dysfunction, inflammation, ischemic and hemorrhagic stroke and cardiac and renal ischemia reperfusion injury.

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A 20-Hydroxyeicosatetraenoic Acid Agonist, N-[20-Hydroxyeicosa-5(z),14(z)-Dienoyl]glycine, Opposes the Fall in Blood Pressure and Vascular Reactivity in Endotoxin-Treated Rats

Cited by 32 publications

References 22 publications

20-Hydroxy-5,8,11,14-eicosatetraenoic Acid Mediates Endothelial Dysfunction via IκB Kinase-Dependent Endothelial Nitric-Oxide Synthase Uncoupling

20-Hydroxy-5,8,11,14-eicosatetraenoic Acid Mediates Endothelial Dysfunction via IκB Kinase-Dependent Endothelial Nitric-Oxide Synthase Uncoupling

20-HETE in the regulation of vascular and cardiac function

Molecular mechanisms in differentiated thyroid cancer

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