Modulation of arteriolar blood flow by inhibitors of arachidonic acid oxidation after thermal injury: possible role for a novel class of vasodilator metabolites.

Proctor, Kenneth G.; Shatkin, Samuel; Kaminski, P. M.; Falck, John R.; Capdevila, Jorge H.

doi:10.1161/01.cir.77.5.1185

Cited by 16 publications

(4 citation statements)

References 27 publications

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“…Stereoisomers exist for each of the HETEs identified in the brain (Kim et al, 1991), and they can have distinctly different biological activity (Fitzpatrick and Murphy, 1989;Fretland and Djuric, 1989;McGiff and Carroll, 1989;Proctor et al, 1989). For instance, the l%(S)-HETE IN BRAIN MICROVESSELS (R) and ( S ) isomers of 12-HETE have disparate effects on Na+,K+-ATPase activity (Schwartzman et al, 1987;Masferrer et al, 1990), vascular tone (Proctor et al, 1988), neutrophil chemotaxis (Cunningham and Woollard, 1987), and platelet aggregation (Croset and Lagarde, 1983). Cerebral microvessels convert arachidonic acid to 12-HETE (Baba et al, 1985;Hambrecht et al, 1987;Moore et al, 1988aMoore et al, , 1989, but no data are available on the stereoisomer that is produced.…”

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confidence: 99%

Brain Micro vessel 12‐Hydroxyeicosatetraenoic Acid Is the (S) Enantiomer and Is Lipoxygenase Derived

Moore¹,

Giordano²,

Kim³

et al. 1991

Journal of Neurochemistry

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12-Hydroxyeicosatetraenoic acid (12-HETE) production from arachidonic acid by cerebral microvessels isolated from perfused adult murine brain was reduced by the lipoxygenase inhibitors baicalein, esculetin, gossypol, nordihydroguaiaretic acid, and quercetin. Except for quercetin and gossypol, the IC50 did not exceed 10 microM. Each inhibitor, except baicalein, also decreased microvessel prostaglandin production when present in concentrations above their IC50 value for 12-HETE. In contrast, inhibitors of the cytochrome P450 monooxygenase system, clotrimazole, metyrapone, and proadifen (SKF-525A), had little effect on microvessel 12-HETE production. Chiral phase HPLC analysis revealed that only the (S) enantiomer of 12-HETE was formed. The major microvessel metabolite of eicosapentaenoic acid co-eluted with 12-hydroxyeicosapentaenoic acid (12-HEPE) on reverse-phase HPLC and the (S) enantiomer of 12-HEPE on chiral phase HPLC. Furthermore, like 12-HETE, 12-HEPE production was blocked by lipoxygenase inhibitors. These studies demonstrate that brain microvessels produce only the (S) enantiomeric 12-hydroxy derivatives of both arachidonic acid and eicosapentaenoic acid by the action of a lipoxygenase that can be selectively inhibited by baicalein. Since arachidonic acid and eicosapentaenoic acid are available to cerebral blood vessels in certain pathological settings, these 12-hydroxy acid lipoxygenase products may mediate some of the cerebrovascular dysfunction that occurs following stroke, brain trauma, or seizures.

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confidence: 99%

Brain Micro vessel 12‐Hydroxyeicosatetraenoic Acid Is the (S) Enantiomer and Is Lipoxygenase Derived

Moore¹,

Giordano²,

Kim³

et al. 1991

Journal of Neurochemistry

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“…Since methysergide inhibited the hind limb vasodilator response to serotonin and CATM, but not to nitroglycerin or verapamil, the present data suggest that methysergide acted in a selective manner to antagonize serotonergic,-like receptors. Although prostaglandins (7,8) and 2-adrenoceptors (9) have been implicated as mediators ofthe increase in local blood flow, neither ICI 1 1855 1 nor meclofenamate altered the hind limb vasodilator response to burn, suggesting that neither #2-adrenoceptors nor cyclooxygenase products appear to mediate this effect. Similarly, atropine, BW 1433U83, diphenhydramine, and ranitidine had no effect on the scald-induced increase in femoral blood flow, suggesting that this response is not mediated by muscarinic, adenosineAl, histaminergic,, or histaminergic2-receptors.…”

Section: Discussionmentioning

confidence: 98%

“…A smaller BSA burn in rats causes only an increase in blood flow to the injured site, a response influenced by surface temperature and injury size (5). Mediation ofthis regional vasodilator response by potassium, prostaglandins, lactate, and activation of f3-adrenoceptors (3,(6)(7)(8)(9) has been suggested. Others consider heat-induced vasodilation a prime component of this response (5).…”

Section: Introductionmentioning

confidence: 99%

Analysis of regional hemodynamic regulation in response to scald injury.

Taheri¹,

Lippton²,

Force³

et al. 1994

J. Clin. Invest.

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Ultrasonic probes were placed around dog femoral arteries to record blood flow. Hind paw scalding with boiling water (5 s) caused a marked increase in ipsilateral femoral blood flow that persisted for the 2-h observation period. Contralateral femoral blood flow and systemic and pulmonary vascular resistances were unchanged. Compared to scald only animals, methysergide pretreatment diminished and shortened the femoral vasodilator response to scald (109±14 vs 243±27 ml/min at 5 min; 59±14 vs 191±31 ml/min at 2 h). Pretreatment with ritanserin, BW A1433U83, atropine, ICI 118551, diphenhydramine, ranitidine, meclofenamate, L-nitro-arginine methyl ester, 3-amino-1,2,4-triazine, and U 37883A had no effect on the increased femoral blood flow response to scald, suggesting this vasodilator response is not dependent upon activation of serotonergic2, adenosineAl, muscarinic, l2-adrenergic, histaminergic1 or histaminergic2 receptors, on cyclooxygenase products, endothelium-derived relaxing factor derived from nitric oxide (NO) synthase III, NO derived from NO synthase II, or KATp channels, respectively. Methysergide given after burn immediately reduced the augmented femoral blood flow to preburn levels, suggesting the vasodilator response to scald is mediated through continual activation of local serotonergicl-like receptors, which may be target site(s) for therapeutic interventions to influence burn-induced hemodynamic alterations. (J. Clin.

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“…Furthermore, several recent reports indicate that the stereoisomers of particular HETEs can have distinctly different biological activities. For instance, the R and S isomers of 12-HETE have been shown to have disparate effects on Na+,K+-ATPase activity (Schwartzman et al, 1987;Masferrer et al, 1990), vascular tone (Proctor et al, 1988), and neutrophil chemotaxis (Cunningham and Woolard, 1987). Therefore, knowledge of whether enantiomers of a given HETE are metabolized in a similar fashion by the cerebral endothelium is of interest.…”

Section: Discussionmentioning

confidence: 99%

Differential Metabolism of Hydroxyeicosatetraenoic Acid Isomers by Mouse Cerebromicrovascular Endothelium

Giordano

Mathur

Moore

1992

Journal of Neurochemistry

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Hydroxyeicosatetraenoic acid (HETE) derivatives of arachidonic acid are produced in the brain and have been implicated as pathologic mediators in various types of brain injury. To understand better their fate in the brain, particularly in cerebral microvessels, several HETEs were incubated with cultured mouse cerebromicrovascular endothelium for 1, 2, and 4 h, followed by HPLC analysis of medium and cellular lipids. 5(S)-, 8(RS)-, and 9(RS)-HETE were not metabolized by the cells, but were extensively incorporated, unmodified, into cell lipids. On the other hand, 11(RS)-, 12(S)-, and 15(S)-HETE were extensively metabolized and only minimally incorporated into cell lipids. Previously, the major 12-HETE metabolite was identified as 8-hydroxyhexadecatrienoic acid. In the present study, we identified the major 11-HETE metabolite as 7-hydroxyhexadecatrienoic acid and the major 15-HETE metabolite as 11-hydroxyhexadecatrienoic acid. omega-3 compounds, 15(S)- and 12(S)-hydroxyeicosapentaenoic acids (HEPE), were also metabolized to more polar compounds, but to a lesser extent than their tetraenoic acid, omega-6 counterparts. Comparison of 5-, 12-, and 15-HETE enantiomers revealed no differences in metabolism or incorporation between the R and S stereoisomers. These data suggest that many isomers of HETE and HEPE can be incorporated into cell lipids or metabolized by pathways that do not distinguish between enantiomers. These pathways, however, are sensitive to the position or number of double bonds and are selective based on the position of the hydroxyl group.

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Modulation of arteriolar blood flow by inhibitors of arachidonic acid oxidation after thermal injury: possible role for a novel class of vasodilator metabolites.

Cited by 16 publications

References 27 publications

Brain Micro vessel 12‐Hydroxyeicosatetraenoic Acid Is the (S) Enantiomer and Is Lipoxygenase Derived

Brain Micro vessel 12‐Hydroxyeicosatetraenoic Acid Is the (S) Enantiomer and Is Lipoxygenase Derived

Analysis of regional hemodynamic regulation in response to scald injury.

Differential Metabolism of Hydroxyeicosatetraenoic Acid Isomers by Mouse Cerebromicrovascular Endothelium

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