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Effect of exogenous 5, 8, 11, 14, 17‐eicosapentaenoic acid on cardiac anaphylaxis
Author(s) -
Juan H.,
Peskar B.A.,
Simmet Th.
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb08961.x
Subject(s) - guinea pig , chemistry , anaphylaxis , thromboxane b2 , thromboxane , vasoconstriction , medicine , eicosapentaenoic acid , leukotriene , leukotriene c4 , endocrinology , prostaglandin , pharmacology , biochemistry , fatty acid , immunology , platelet , allergy , polyunsaturated fatty acid , asthma
1 The effects of infusions of eicosapentaenoic acid (EPA) (6 × 10 −8 mol min −1 and 15 × 10 −8 mol min −1 ) on the coronary constriction and the release of immunoreactive sulphidopeptide‐leukotrienes (SP‐LT), thromboxane B 2 (TXB 2 ) and 6‐keto‐prostaglandin F 1α (PGF 1α ) 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 × 10 −8 mol min −1 ) significantly shortened the average duration of antigen‐induced arrhythmias. 3 EPA dose‐dependently decreased release of immunoreactive TXB 2 and 6‐keto‐PGF 1α 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 × 10 −7 mol min −1 ) 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 C 4 (LTC 4 ), LTD 4 and LTE 4 . In perfusates from hearts treated with EPA infusions, additional immunoreactivity was detected comigrating with LTC 5 , LTD 5 and LTE 5 . In addition to immunoreactivity migrating with LTB 4 , 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 LTB 5 . 6 Exogenous LTC 5 (1 × 10 −12 mol min −1 and 20 × 10 −12 mol min −1 ) induced dose‐dependent reductions of coronary flow and was found to be a slightly weaker constrictor than LTC 4 , but no significant differences were observed. Coronary vasoconstriction elicited by infusion of exogenous LTC 4 (20 × 10 −12 mol min −1 ) was dose‐dependently inhibited by infusions of EPA. However, the negative inotropic effect of LTC 4 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 LTC 4 ‐induced coronary constriction, it seems possible, that EPA might act as a functional antagonist of vasoconstrictor eicosanoids including EPA‐derived SP‐LT.