ACTINOMYCIN-D BLOCKS INTERLEUKIN-1-ALPHA-INDUCED PIAL ARTERIOLAR DILATION AND INCREASED PROSTANOID PRODUCTION IN NEWBORN PIGS

Effects of protein synthesis and cyclooxygenase inhibitors on interleukin-1alpha (IL-1alpha)- and histamine-induced pial arteriolar dilation and cerebrospinal fluid (CSF) prostanoid increases were examined in anesthetized piglets using closed cranial windows. Topical IL-1alpha (10.8 mug) increased pial arteriolar diameter from 15 to 30 min after its infusion, and enhanced CSF prostanoids. Topical protein synthesis inhibitor, actinomycin D, at a concentration of 10(-8) M attenuated and 10(-6) M completely blocked both IL-1alpha-induced vasodilation and CSF prostanoid increase. Inhibition of prostaglandin H synthases with indomethacin blocked both vasodilation and CSF prostanoid increase by IL-1alpha. Topical histamine (10(-6) M) also increased pial arteriolar diameter and CSF prostanoids but without the delay seen between IL-1alpha infusion and responses. These histamine effects were not modified by coinfusion of actinomycin D but blocked by indomethacin. These results suggest that, although IL-1alpha and histamine do share the same mechanism insofar as activation of prostaglandin synthesis is concerned, an additional step appears to be involved for IL-1alpha, likely involving de novo protein synthesis.