Abstract

Studies were conducted in Langendorff-perfused rabbit hearts to assess the actions of phorbol myristate acetate (PMA)-stimulated neutrophils on coronary vascular resistance and left ventricular contraction. Whereas PMA or neutrophils alone were without effects in this preparation, PMA-stimulated neutrophils evoked pronounced increases in coronary resistance and decreases in left-ventricular pulse pressure. The changes in coronary resistance and left ventricular pulse pressure induced by PMA-stimulated neutrophils were attenuated by scavengers of superoxide anion (superoxide dismutase), hydrogen peroxide (catalase) and hydroxyl radical (dimethylthiourea), thereby implying a pivotal role for hydroxyl radical. Inasmuch as the increase in coronary resistance could be reversed partially by the nonspecific vasodilator, sodium nitroprusside, and inasmuch as none of the free radical scavengers influenced PMA-induced neutrophil aggregation, the increase in coronary resistance evoked by PMA-stimulated neutrophils is related in part to oxygen radical-mediated coronary vasoconstriction.