Endothelium-derived hyperpolarizing factor in coronary microcirculation: responses to arachidonic acid

Oltman, Christine L.; Kane, Neal L.; Fudge, Jonathon L.; Weintraub, Neal L.; Dellsperger, Kevin C.

doi:10.1152/ajpheart.2001.281.4.h1553

Cited by 16 publications

(15 citation statements)

References 21 publications

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“…25 However, arachidonic acid-mediated microvascular dilatation in canine coronary arteries includes stimulation of NO production. 20 Our findings suggest that simvastatin may increase NO production or release by increasing the formation of certain long-chain polyunsaturated fatty acids and their eicosanoid metabolites.…”

Section: Jula Et Al Effects Of Diet and Simvastatin On Fatty Acid Commentioning

confidence: 64%

“…19 Recent findings also suggest that endothelium-derived hyperpolarizing factor, an important mediator of vasodilatation especially in small arteries, may be a product of the non-cyclo-oxygenase-mediated metabolism of arachidonic acid. 20 Further, as discussed, some PUFAs are precursors for eicosanoids, with important effects on vascular tone and hemostasis. Depending on the tissue, an increased availability of arachidonic acid could result in increased formation of prostacyclin (endothelium) and thromboxane (platelets) in a reaction chain initiated by cyclo-oxygenase enzymes.…”

Section: Jula Et Al Effects Of Diet and Simvastatin On Fatty Acid Commentioning

confidence: 99%

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Effects of Diet and Simvastatin on Fatty Acid Composition in Hypercholesterolemic Men

Jula

Marniemi

Rönnemaa

et al. 2005

ATVB

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Objective-To explore the separate and combined effects of simvastatin and a low-saturated diet rich in ␣-linolenic acid on serum fatty acids. Methods and Results-120 hypercholesterolemic men were randomly allocated to a habitual diet or dietary treatment group and to receive, in random order, simvastatin 20 mg/d or placebo, each for 12 weeks, in a double-blind manner. Dietary treatment decreased proportions from total fatty acids of palmitic acid (C16:0) by 3.3% (PϽ0.05), stearic acid (C18:0) by 3.7% (PϽ0.05) and increased proportions of oleic acid (C18:1n-9) by 4.2% (PϽ0.01), and ␣-linolenic acid (C18:3n-3) by 29.8% (PϽ0.001). Simvastatin decreased proportions from total fatty acids of palmitic acid by 2.0% (PϽ0.01), linoleic acid (C18:2n-6) by 5.3% (PϽ0.001), and ␣-linolenic acid by 6.8% (PϽ0.05), and increased proportions of ␥-linolenic acid (C18:3n-6) by 11.1% (PϽ0.001), dihomo-␥-linolenic acid (C20:3n-6) by 4.2% (PϽ0.01), arachidonic acid (C20:4n-6) by 14.2% (PϽ0.001), and the sum of long-chain polyunsaturated fatty acids (C20-22) by 9.0% (PϽ0.001). Simvastatin increased ratios of stearic to palmitic, ␥-linolenic to linoleic, and arachidonic to dihomo-␥-linolenic acid by 7.6%, 17.0%, and 10.0% (PϽ0.001 for all), respectively, suggesting increased fatty acid elongase and ⌬6-and ⌬5-desaturase enzyme activities. Conclusions-Increased

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Section: Jula Et Al Effects Of Diet and Simvastatin On Fatty Acid Commentioning

confidence: 64%

Section: Jula Et Al Effects Of Diet and Simvastatin On Fatty Acid Commentioning

confidence: 99%

Effects of Diet and Simvastatin on Fatty Acid Composition in Hypercholesterolemic Men

Jula

Marniemi

Rönnemaa

et al. 2005

ATVB

View full text Add to dashboard Cite

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“…However, in the majority of vascular beds [11,54,62,103,107], catalase does not inhibit EDHF responses.…”

Section: Carbon Monoxidementioning

confidence: 93%

Endothelium-derived hyperpolarising factors and associated pathways: a synopsis

Edwards

Félétou

Weston

2010

Pflugers Arch - Eur J Physiol

323

332

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The term endothelium-derived hyperpolarising factor (EDHF) was introduced in 1987 to describe the hypothetical factor responsible for myocyte hyperpolarisations not associated with nitric oxide (EDRF) or prostacyclin. Two broad categories of EDHF response exist. The classical EDHF pathway is blocked by apamin plus TRAM-34 but not by apamin plus iberiotoxin and is associated with endothelial cell hyperpolarisation. This follows an increase in intracellular [Ca(2+)] and the opening of endothelial SK(Ca) and IK(Ca) channels preferentially located in caveolae and in endothelial cell projections through the internal elastic lamina, respectively. In some vessels, endothelial hyperpolarisations are transmitted to myocytes through myoendothelial gap junctions without involving any EDHF. In others, the K(+) that effluxes through SK(Ca) activates myocytic and endothelial Ba(2+)-sensitive K(IR) channels leading to myocyte hyperpolarisation. K(+) effluxing through IK(Ca) activates ouabain-sensitive Na(+)/K(+)-ATPases generating further myocyte hyperpolarisation. For the classical pathway, the hyperpolarising "factor" involved is the K(+) that effluxes through endothelial K(Ca) channels. During vessel contraction, K(+) efflux through activated myocyte BK(Ca) channels generates intravascular K(+) clouds. These compromise activation of Na(+)/K(+)-ATPases and K(IR) channels by endothelium-derived K(+) and increase the importance of gap junctional electrical coupling in myocyte hyperpolarisations. The second category of EDHF pathway does not require endothelial hyperpolarisation. It involves the endothelial release of factors that include NO, HNO, H(2)O(2) and vasoactive peptides as well as prostacyclin and epoxyeicosatrienoic acids. These hyperpolarise myocytes by opening various populations of myocyte potassium channels, but predominantly BK(Ca) and/or K(ATP), which are sensitive to blockade by iberiotoxin or glibenclamide, respectively.

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“…A standard in vitro pressurized arteriole preparation was used to study coronary microvessels (15,16). Ventricular microvessels 75-175 m intraluminal…”

Section: Methodsmentioning

confidence: 99%

“…Responses have been determined to be dependent on vessel size, animal species, and regional circulation. Our group reported that in the dog, arachidonic acid (AA)-induced dilatory responses in the coronary microcirculation are mediated through redundant pathways (15). However, Hein and colleagues (7) demonstrated that in the porcine coronary microcirculation, dilation may be mediated through COX.…”

mentioning

confidence: 99%

Reactive oxygen species mediate arachidonic acid-induced dilation in porcine coronary microvessels

Oltman

Kane²,

Miller³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Reactive oxygen species mediate arachidonic acid: induced dilation in porcine coronary microvessels. Am J Physiol Heart Circ Physiol 285: H2309-H2315, 2003. First published July 17, 2003 10.1152/ajpheart.00456.2003.-Reactive oxygen species (ROS) have been proposed to mediate vasodilation in the microcirculation. We investigated the role of ROS in arachidonic acid (AA)-induced coronary microvascular dilation. Porcine epicardial coronary arterioles (110 Ϯ 4 m diameter) were mounted onto pipettes in oxygenated Krebs buffer. Vessels were incubated with vehicle or 1 mM Tiron (a nonselective ROS scavenger), 250 U/ml polyethylene-glycolated (PEG)-superoxide dismutase (SOD; an O 2 Ϫ scavenger), 250 U/ml PEG-catalase (a H2O2 scavenger), or the cyclooxygenase (COX) inhibitors indomethacin (10 M) or diclofenac (10 M) for 30 min. After endothelin constriction (30-60% of resting diameter), cumulative concentrations of AA (10 Ϫ10 -10 Ϫ5 M) were added and internal diameters measured by video microscopy. AA (10 Ϫ7 M) produced 37 Ϯ 6% dilation, which was eliminated by the administration of indomethacin (4 Ϯ 7%, P Ͻ 0.05) or diclofenac (Ϫ8 Ϯ 8%, P Ͻ 0.05), as well as by Tiron (Ϫ4 Ϯ 5%, P Ͻ 0.05), PEG-SOD (Ϫ10 Ϯ 6%, P Ͻ 0.05), or PEG-catalase (1 Ϯ 4%, P Ͻ 0.05). Incubation of small coronary arteries with [ 3 H]AA resulted in the formation of prostaglandins, which was blocked by indomethacin. In separate studies in microvessels, AA induced concentration-dependent increases in fluorescence of the oxidant-sensitive probe dichlorodihydrofluorescein diacetate, which was inhibited by pretreatment with indomethacin or by SOD ϩ catalase. We conclude that in porcine coronary microvessels, COX-derived ROS contribute to AA-induced vasodilation.cyclooxygenase; coronary microcirculation THE VASCULAR ENDOTHELIUM generates a number of vasoactive agents that are important in the regulation of coronary blood flow. These putative agents may be produced through several enzyme pathways, including nitric oxide synthase (NOS), cyclooxygenase (COX), lipoxygenase (LOX), and the cytochrome P-450 monooxygenase (CYP-450) systems. Responses have been determined to be dependent on vessel size, animal species, and regional circulation. Our group reported that in the dog, arachidonic acid (AA)-induced dilatory responses in the coronary microcirculation are mediated through redundant pathways (15). However, Hein and colleagues (7) demonstrated that in the porcine coronary microcirculation, dilation may be mediated through COX.Several groups have proposed that reactive oxygen species (ROS) are mediators of microvascular dilation (1,12,18). Putative ROS mediators include superoxide anions, hydrogen peroxide, and hydroxyl radicals. Metabolism of AA by COX, LOX, or CYP-P450 may be associated with the production of oxygen-derived free radicals (5, 8). In the microcirculation of the brain, ROS derived through metabolism of AA have been suggested to mediate vasodilatory responses to bradykinin (3).Mediators of AA-induced relaxation in the coronary microcirculation rem...

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Endothelium-derived hyperpolarizing factor in coronary microcirculation: responses to arachidonic acid

Cited by 16 publications

References 21 publications

Effects of Diet and Simvastatin on Fatty Acid Composition in Hypercholesterolemic Men

Effects of Diet and Simvastatin on Fatty Acid Composition in Hypercholesterolemic Men

Endothelium-derived hyperpolarising factors and associated pathways: a synopsis

Reactive oxygen species mediate arachidonic acid-induced dilation in porcine coronary microvessels

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