Membrane-bound lipoxygenase of rat cerebral microvessels

Baba, Akemichi; Kimoto, Minoru; Tatsuno, Tohru; Inoue, Teruyoshi; Iwata, Heitaroh

doi:10.1016/s0006-291x(85)80156-x

Cited by 29 publications

(27 citation statements)

References 16 publications

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“…Miyamoto et al (1987b) have demonstrated a relative enrichment of 5-lipoxygenase activity in the thalamus and hypothalamus, and immunohistochemical evidence suggests that neurons of the hypothalamus contain a product of the 5-lipoxygenase pathway, leukotriene C4 (Lindgren et al, 1984). We and others have reported that isolated cerebral microvessels can convert arachidonic acid to 12-HETE (Hambrecht et al, 1987;Moore et al, 1988a,b) and Baba et al (1985) have detected 12-lipoxygenase activity in cerebral microvessels.…”

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confidence: 88%

Murine cerebral microvascular endothelium incorporate and metabolize 12‐hydroxyeicosatetraenoic acid

Moore

Prokuski

Figard

et al. 1988

Journal Cellular Physiology

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Cultured murine cerebromicrovascular endothelial cells were employed to study the metabolism of 12-hydroxyeicosatetraenoic acid (12-HETE) in an in vitro model of the blood-brain barrier. These endothelial cells convert 12-HETE to at least four, more polar compounds. Analysis of the least polar and predominant metabolite by gas chromatography combined with chemical ionization and electron impact mass spectrometry of reduced and nonreduced derivatives indicate that the compound is 8-hydroxyhexadecatrienoic acid (8-HHDTrE). The uptake of 12-HETE into cell phospholipids peaks at 2 hr, and is not saturable up to the highest concentration tested, 5 microM. Seventy-five to 92% of this 12-HETE is incorporated into phosphatidylcholine, while the remainder is divided between the inositol and ethanolamine phospholipids. Incorporation into neutral lipids is slower, with radioactivity gradually accumulating in triglycerides over 24 hr. Saponification of cell lipids demonstrated that not only 12-HETE, but also its major metabolite, 8-HHDTrE, is incorporated into the cell lipids. Prostacyclin and prostaglandin E2 production by the cerebral endothelial cells is inhibited by up to 56% with 1 microM and 90% with 5 microM 12-HETE. These data demonstrate that 12-HETE is actively metabolized by cerebral endothelium and suggest at least two mechanisms through which 12-HETE may alter cerebromicrovascular function: 1) incorporation into cerebral endothelial membranes and 2) inhibition of cerebral endothelial prostaglandin production. Conversion of 12-HETE to more polar compounds, particularly 8-HHDTrE, may be interpreted as either the inactivation of 12-HETE or the production of additional, biological mediators.

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mentioning

confidence: 88%

Murine cerebral microvascular endothelium incorporate and metabolize 12‐hydroxyeicosatetraenoic acid

Moore

Prokuski

Figard

et al. 1988

Journal Cellular Physiology

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“…22 The concentration of 6-keto-PGF 1␣ in medium derived from incubation of aortic rings in indomethacin-containing buffer without exogenous PGH 2 was Ͻ3% of the concentration in medium derived from incubations carried out in the presence of exogenous PGH 2 . Hence, Ն97% of the 6-keto-PGF 1␣ in the incubation medium with PGH 2 arises from exogenous PGH 2 …”

Section: Measurement Of Conversion Of Pgh 2 To Pgi 2 By Rings Of Thormentioning

confidence: 99%

“…[1][2][3] The product of this reaction is 12-HPETE, which undergoes spontaneous or peroxidase-catalyzed reduction to 12-HETE. 4 Both 12-HPETE and 12-HETE are capable of influencing vascular functions.…”

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confidence: 99%

“…6,11 Reports that lipoxygenase inhibitors attenuate the vascular actions of Ang II 9,10,12 and lower blood pressure in hypertensive rats 11,13,14 incriminate lipoxygenase-derived eicosanoids in the mechanisms of arterial hypertension. Because 12-HPETE and other hydroperoxides arising from polyunsaturated fatty acids via metabolism by lipoxygenase(s) inhibit PGI 2 , 5,15 excessive expression of lipoxygenase or lipoxygenases may promote elevation of blood pressure by weakening the activity of antihypertensive mechanisms mediated by PGI 2 . 16 If so, lipoxygenase inhibitors may lower blood pressure in such settings by fostering production of PGI 2 .…”

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confidence: 99%

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Prostaglandin I ₂ Contributes to the Vasodepressor Effect of Baicalein in Hypertensive Rats

1998

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Abstract-Lipoxygenase inhibitors reduce blood pressure in hypertensive rats. The vasodepressor effect of lipoxygenase inhibitors may be related to increased production of prostaglandin (PG) I 2 since lipoxygenase-derived fatty acid hydroperoxides inhibit PGI 2 synthase. This hypothesis was examined in rats made hypertensive by infusion of angiotensin II (200 ng/min IP) for 12 to 14 days. In hypertensive but not in normotensive rats, the lipoxygenase inhibitor baicalein (60 mg/kg SC) increased (PϽ.05) the conversion of exogenous PGH 2 to PGI 2 by aortic segments, the release of 6-keto-PGF 1␣ by aortic rings, the concentration of 6-keto-PGF 1␣ in blood, and the renal excretion of 6-keto-PGF 1␣ . Treatment with baicalein did not affect the blood pressure of normotensive rats but decreased the blood pressure of hypertensive rats from 177Ϯ8 to 133Ϯ9 mm Hg after 120 minutes (PϽ.05). Also, the lipoxygenase inhibitor cinnamyl-3,4-dihydroxy-␣-cyanocinnamate (8 mg/kg SC) was without effect on the blood pressure of normotensive rats but decreased the blood pressure of hypertensive rats from 182Ϯ4 to 139Ϯ8 mm Hg (PϽ.05). However, the blood pressure of hypertensive rats pretreated with indomethacin (5 mg/kg IV) was affected by neither baicalein nor cinnamyl-3,4-dihydroxy-␣-cyanocinnamate. Moreover, in hypertensive rats in which baicalein had decreased blood pressure to 148Ϯ6 mm Hg, the administration of rabbit serum containing antibodies against 5,6-dihydro-PGI 2 (0.3 mL IV) partially reversed the response to baicalein, increasing blood pressure to 179Ϯ7 mm Hg within 20 minutes (PϽ.05). The antibodies also were shown to block the vasodepressor effect of PGI 2 but not of PGE 2 . Collectively, these data suggest contribution of PGI 2 to the acute antihypertensive effect of baicalein in rats with angiotensin II-induced hypertension.

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“…156 -On the other hand, there were claims that in human 161 and in calf 162 vascular cells the generation of prostacyclin is only partially 161 inhibited by indomethacin, if at all. 162 In further studies, 12-HETE and other monohydroxylated derivatives of AA were isolated from human, 161 rabbit, 163 and rat 164 blood vessels. The origin of hydroxylated lipids and the preferential routes for their oxygenation within the vascular wall remain an interesting area for investigation.…”

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confidence: 99%

Mediators produced by the endothelial cell.

1988

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SUMMARY This review discusses the role of three mediators, synthesized by vascular endotheiial cells, that help to keep the surface of the normal endotheliuin nonthrombogenic. The first is prostacydin, a product of arachldonic add metabolism discovered hi 1976. This labile prostanoid, with a half-life of approximately 3 minutes, relaxes vascular smooth musde and inhibits the aggregation of blood platelets. Prostacydin and its analogues are currently being tested clinically for use hi cardiovascular diseases such as primary pulmonary hypertension. The second mediator discussed is endothelium-derived relaxing factor (EDRF), discovered in 1980, which also relaxes smooth muscle and inhibits the aggregation and adhesion of platelets. Substances that stimulate the release of EDRF include acetykhoUne, bradykinin, and adenosine 5'-diphosphate. EDRF is even more labile than prostacydin, with a half-life of about 6 seconds, and it has recently been identified as nitric oxide. Prostacydin and EDRF are released together following stimulation of endothelial receptors and synergize to inhibit platelet aggregation. 13-Hydroxy-9,11-octadecadienoic add, a third suggested mediator, is not released but acts from inside the cell to make the endothelial surface nonadhesive for circulating blood ceils. It is proposed that these three mediators form the endothelial defense mechanism against blood-borne cells and chemicals and that breakdown of this barrier results in diseases such as hypertension and atherosclerosis. (Hypertension 12: 530-548,1988) KEY WORDS • prostacyclin • endothelium-derived relaxing factor • thromboresistance • 13-hydroxy-9,ll-octadecadienoic add • endothelin • 6-keto-prostaglandin E,

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Membrane-bound lipoxygenase of rat cerebral microvessels

Cited by 29 publications

References 16 publications

Murine cerebral microvascular endothelium incorporate and metabolize 12‐hydroxyeicosatetraenoic acid

Murine cerebral microvascular endothelium incorporate and metabolize 12‐hydroxyeicosatetraenoic acid

Prostaglandin I ₂ Contributes to the Vasodepressor Effect of Baicalein in Hypertensive Rats

Mediators produced by the endothelial cell.

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Membrane-bound lipoxygenase of rat cerebral microvessels

Cited by 29 publications

References 16 publications

Murine cerebral microvascular endothelium incorporate and metabolize 12‐hydroxyeicosatetraenoic acid

Murine cerebral microvascular endothelium incorporate and metabolize 12‐hydroxyeicosatetraenoic acid

Prostaglandin I 2 Contributes to the Vasodepressor Effect of Baicalein in Hypertensive Rats

Mediators produced by the endothelial cell.

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Prostaglandin I ₂ Contributes to the Vasodepressor Effect of Baicalein in Hypertensive Rats