Effect of inhibition of synthesis and receptor antagonism of SRS‐ A in cardiac anaphylaxis

Aehringhaus, U.; Peskar, Bernhard A.; Wittenberg, H. R.; Wölbling, R.H.

doi:10.1111/j.1476-5381.1983.tb11051.x

Cited by 40 publications

(16 citation statements)

References 28 publications

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“…USA 84 (1987) 0 anaphylaxis (11)(12)(13)(14). It has also been documented that inhibitors of leukotriene formation can prevent several anaphylactic responses (29)(30)(31) …”

Section: %1mentioning

confidence: 99%

Endogenous leukotriene D4 formation during anaphylactic shock in the guinea pig.

Keppler¹,

Örning²,

Bernström³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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Experiments on the metabolism and excretion of i.v. administered selectively labeled [3H8]1eukotriene C4 in bile duct-cannulated guinea pigs indicated predominantly biliary excretion of tritium. The major leukotriene metabolite in bile was identified as leukotriene D4. By monitoring leukotriene excretion radioimmunochromatographically, it was shown that guinea pigs suffering from anaphylactic shock produce leukotriene D4 endogenously. Immunological challenge of animals sensitized to ovalbumin was accompahied by an increase of biliary leukotriene D4 concentrations from 10 ± 1 to 86 ± 10 nM (mean ± SEM, n = 5, P < 0.001). When considering that bile flow was decreased to abobt half after challenge, the excretion rate of leukotriene D4 in bile increased from 0.88 ± 0.16 before to 3.18 ± 0.38 pmolmin-'-kg-' after challenge (mean ± SEM, n = 5, P < 0.002). It is concluded that systemic anaphylaxis in the guinea pig is associated with endogenous generation of leukotriene C4 (Up to 1 nmol/kg during a 30-min period after the challenge).Leukotriene C4 (LTC4) is a biologically active substance presumed to play major roles as a mediator of allergic and anaphylactic reactions (1, 2). It is formed by basophilic (3) and eosinophilic leukocytes (4), monocytes (5), macrophages (6), and mast cells (7). In cells having IgE receptors, bridging of these receptors by divalent anti-IgE receptor antibodies or by interaction between receptor-bound IgE and anti-IgE will induce LTC4 formation (5-7). Leukotriene formation has also been demonstrated in other in vitro models of immediate hypersensitivity (8-10). The biological actions of LTC4 comprise induction of airway obstruction, constriction of coronary arteries, hypotension, and plasma extravasation (11)(12)(13)(14). Leukotriene formation in vivo may mediate anaphylactic shock symptoms and cause the death of an animal. To prove the presumed mediator role of this substance in anaphylactic reactions, it is necessary to demonstrate its endogenous formation during anaphylaxis. Studies on LTC4 metabolism have revealed rapid catabolism by various transformations of the peptide substituent (15). Three metabolites have been demonstrated to be excreted as end-products: leukotriene E4 (LTE4) (16) in man and N-acetyl-LTE4 plus N-acetyl-11-trans-LTE4 (17) in the rat. By monitoring biliary N-acetyl-LTE4 levels, endogenous leukotriene formation in the rat was demonstrated in vivo after tissue trauma and endotoxin shock (18,19). We now wish to report evidence for endogenous LTC4 production during anaphylactic shock in guinea pigs.

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“…USA 84 (1987) 0 anaphylaxis (11)(12)(13)(14). It has also been documented that inhibitors of leukotriene formation can prevent several anaphylactic responses (29)(30)(31) …”

Section: %1mentioning

confidence: 99%

Endogenous leukotriene D4 formation during anaphylactic shock in the guinea pig.

Keppler¹,

Örning²,

Bernström³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition, electrocardiographic changes have been found that are similar to those observed in man during anaphylaxis (Capurro & Levi, 1975). Furthermore, upon immunological challenge, various mediators, which could be responsible for the observed changes in cardiac function, like histamine (Brocklehurst, 1960;Feigen & Prager, 1969) slowreacting substance of anaphylaxis (SRS-A) (Brocklehurst, 1960;Liebig et al, 1975) or sulphidopeptideleukotrienes (SP-LT) (Aehringhaus et al, 1983), platelet-activating factor (Paf-acether) , prostaglandins (Liebig et al, 1975;Levi et al, 1976;Anhut et al, 1978;Peskar et al, 1979;Allan & Levi, 1981), and thromboxane B2 (TXB2) (Anhut et al, 1977;Allan & Levi, 1981), the stable degradation product of the biologically active TXA2, have been detected in perfusates of anaphylactic guinea-pig hearts.…”

Section: Introductionmentioning

confidence: 71%

“…In fact the validity of the method in this particular system has been repeatedly checked by correlation to bioassay data (Aehringhaus et al, 1983). Relative cross-reaction of LTC, with the anti SP-LT antiserum was 99%.…”

Section: Methodsmentioning

confidence: 96%

“…TXB2 and 6-keto-PGF,6 in the perfusates were also determined radioimmunologically, as described previously (Anhut et al, 1977;Peskar et al, 1979;Aehringhaus et al, 1983 …”

Section: Methodsmentioning

confidence: 99%

“…However, release of A 7-6-keto-PGF1<, the degradation product of PGI3, from human umbilical artery incubated with EPA has been reported (Dyerberg et al, 1981), as well as excretion ofa urinary PGI3 metabolite and release ofTXA3 from human platelets, both from subjects who had ingested large quantities of marine oils (Fischer & Weber, 1983;. As in the guinea-pig lung, thromboxane release predominates during anaphylaxis in guinea-pig hearts (Dawson et al, 1976;Anhut et al, 1977;Allan & Levi, 1981;Aehringhaus et al, 1983), while under basal conditions lungs (Gryglewski et al, 1978) and hearts (Schror et al, 1978) release mainly PGI2. TXA2 is known to induce coronary vasospasm without direct negative inotropic effects in guinea-pig isolated, working hearts (Terashita et al, 1978).…”

Section: Exogenous Sulphidopeptide-leukotrienesmentioning

confidence: 99%

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Effect of exogenous 5, 8, 11, 14, 17‐eicosapentaenoic acid on cardiac anaphylaxis

Juan

Peskar

Simmet

1987

British J Pharmacology

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1 The effects of infusions of eicosapentaenoic acid (EPA) (6 x 10-8 mol min-' and 15 x 10-8 mol min-I) on the coronary constriction and the release of immunoreactive sulphidopeptideleukotrienes (SP-LT), thromboxane B2(TXB2) and 6-keto-prostaglandin F,,(PGF,) from perfused anaphylactic guinea-pig hearts were investigated.2 EPA dose-dependently inhibited the profound early coronary flow reduction after antigen injection. The less pronounced late phase of anaphylactic coronary flow reduction was, however, not significantly affected. EPA (15 x 10-8 molmin') significantly shortened the average duration of antigen-induced arrhythmias. 3 EPA dose-dependently decreased release of immunoreactive TXB2 and 6-keto-PGF,6 from anaphylactic guinea-pig hearts. 4 Release of immunoreactive SP-LT was dose-dependently increased after antigen challenge in the presence of EPA. Inhibition of the release of SP-LT by the lipoxygenase inhibitor esculetin (1 x 10-' mol min ') was accompanied by a significant attenuation of flow reduction during the late phase of anaphylactic vasoconstriction. 5 Reversed phase h.p.l.c. of perfusates from anaphylactic guinea-pig hearts revealed immunoreactivity comigrating with authentic leukotriene C4 (LTC4), LTD4 and LTE4. In perfusates from hearts treated with EPA infusions, additional immunoreactivity was detected comigrating with LTC5, LTD5 and LTE5. In addition to immunoreactivity migrating with LTB4, as observed in control heart perfusates, in perfusates from EPA-treated hearts, a second peak was observed, which coincides with the retention time described for LTB5. 6 Exogenous LTC5 (1 x 10-12 mol min-' and 20 x 10-2 molmin-') induced dose-dependent reductions of coronary flow and was found to be a slightly weaker constrictor than LTC4, but no significant differences were observed. Coronary vasoconstriction elicited by infusion of exogenous LTC4 (20 x 10-12 mol minr') was dose-dependently inhibited by infusions of EPA. Howevet, the negative inotropic effect of LTC4 remained unaffected. 7 Thus, in the isolated anaphylactic heart of the guinea-pig exogenous EPA was effectively metabolized via the 5-lipoxygenase pathway whereas the cyclo-oxygenase pathway of polyunsaturated fatty acid metabolism was found to be inhibited. The results are in agreement with the suggestion that cyclo-oxygenase products are mediators of the early phase of the anaphylactic coronary constriction, while vasoconstrictor SP-LT are involved in the later phase. However, in spite of enhanced release of SP-LT, EPA infusion did not result in increased coronary constriction. Considering the fact that EPA antagonizes LTC4-induced coronary constriction, it seems possible, that EPA might act as a functional antagonist of vasoconstrictor eicosanoids including EPA-derived SP-LT.

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Leukotriene C4 Is Released from the Anaphylactic Heart: A Case for Its Direct Negative Inotropic Effect

Levi

Hattori

Burke

et al. 1985

Prostaglandins, Leukotrienes, and Lipoxins

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Effect of inhibition of synthesis and receptor antagonism of SRS‐ A in cardiac anaphylaxis

Cited by 40 publications

References 28 publications

Endogenous leukotriene D4 formation during anaphylactic shock in the guinea pig.

Endogenous leukotriene D4 formation during anaphylactic shock in the guinea pig.

Effect of exogenous 5, 8, 11, 14, 17‐eicosapentaenoic acid on cardiac anaphylaxis

Leukotriene C4 Is Released from the Anaphylactic Heart: A Case for Its Direct Negative Inotropic Effect

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