Influence of intracellular Ca2+-overload in eicosanoid synthesis of the myocardium.
Intracellular Ca2+-overload in the myocardium can be induced not only after readmission of Ca2+-containing fluid to rat hearts previously perfused with a Ca2+-free buffer, a phenomenon called "the calcium paradox", but also during administration of a Ca2+-ionophore to cardiac tissue. In rat hearts, the myocardial damage induced by the Ca2+ paradox was more pronounced than that after administration of the Ca2+-ionophore A23187, as indicated by the amount of lactate dehydrogenase released. The accumulation of NEFA, and especially arachidonic acid, was greater during the Ca2+ paradox than after the administration of the Ca2+-ionophore. Administration of the Ca2+-ionophore resulted in a considerable release of 6-keto-F1 alpha (the stable breakdown product of prostacylclin), and LTD4 and LTE4 (breakdown products of LTC4). In contrast, the formation of eicosanoids was absent during the Ca2+ paradox. It is concluded that the relation between Ca2+-overload and accumulation of arachidonic acid is ambiguous and that there is no close relation between the amount of arachidonic acid accumulated and the formation of eicosanoids in Ca2+-overloaded tissue. The absence of eicosanoid formation during the Ca2+ paradox might be explained by compartmentation of the arachidonic acid accumulation and its converting enzymes or impairment of the enzymatic machinery required for eicosanoid synthesis.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011917:Rats, Inbred Lew
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D016718:Arachidonic Acid; D000001:Calcimycin; D007770:L-Lactate Dehydrogenase; D002118:Calcium