Negative inotropic effect of leukotrienes: leukotrienes C4 and D4 inhibit calcium-dependent contractile responses in potassium-depolarized guinea-pig myocardium.

摘要: The effects of the sulfidopeptide leukotrienes (LTs) on contractile response electrically paced guinea-pig right ventricular papillary muscles in vitro were studied. LTs caused a concentration-dependent (1 nM-20 microM) negative inotropic effect; order relative potency was LTC4 greater than or equal to LTD4 LTE4. A maximal 30% decrease contractility occurred with 1 microM LTC4. LT-induced force not mediated by cyclooxygenase products arachidonic acid cascade, as it influenced indomethacin (14 microM). On other hand, slow-reacting substance-antagonist compound FPL 55712 (480 nM) marked shift concentration-response curve. Because effect attenuated increasing [Ca++]o, we next assessed under conditions which myocardial depends solely slow inward Ca++ current. As model, used isoproterenol- histamine-induced restoration rendered inexcitable 22 mMK+. (16-480 and (20-600nM) inhibited dose-dependent manner; 90% inhibition 0.48 This reversed an elevation [Ca++]o from 1.8 5.4 mM prevented nM). In maintained at [K+]o, (160 480 shifted force-frequency curve (0.1-2 Hz) downwards parallel fashion; similar alteration obtained lowering mM.