NITRIC-OXIDE AND PROSTAGLANDINS INTERACT TO MEDIATE ARTERIOLAR DILATION DURING CORTICAL SPREADING DEPRESSION

We examined whether blockade of prostaglandin synthesis by indomethaci n could attenuate the effect of nitric oxide synthase (NOS) inhibition on cerebral arteriolar dilation during cortical spreading depression (CSD). CSD was induced by microinjection of 5% (670 mM) KCl onto the c erebral cortex of anesthetized adult rabbits. A closed cranial window and intravital microscopy were used to measure pial arteriolar diamete r, and NOS activity was determined by the conversion assay of [C-14]ar ginine to [C-14]citrulline. CSD dilated pial arterioles by 47 +/- 3% ( baseline = 80-88 mu m) (n = 21, P < 0.05), and inhibition of NOS by NG -nitro-L-arginine (L-NNA) (15 mg/kg iv) reduced dilation during CSD by over one-half(n = 8, P < 0.05) without altering the onset latency to CSD. After indomethacin administration (15 mg/kg iv), CSD dilated arte rioles from 73 +/- 2 to 152 +/- 6 mu m (n = 4, P < 0.05). However, aft er administration of both indomethacin and L-NNA (n = 5), CSD-induced arteriolar dilation was not different from the situation where indomet hacin alone was given. Thus indomethacin completely abolished the inhi bitory effect of L-NNA on CSD-induced dilation. Administration of L-NN A inhibited NOS activity in brain cortex almost completely (n = 8, P < 0.05), whereas indomethacin itself had no effect (n = 8). In addition , L-NNA inhibited topical acetylcholine (10(-5) M)-induced arteriolar dilation (n = 3, P < 0.05), and this effect was not altered by indomet hacin (n = 4). In summary, L-NNA reduced arteriolar dilation during CS D. However, after administration of indomethacin, L-NNA does not reduc e CSD-induced arteriolar dilation.