The mechanism of pial arteriolar constriction during post-cortical spreading depression (CSD) was examined in anesthetized adult rabbits. Using a closed cranial window and intravital microscopy, the diameter of a pial arteriole was determined. A single CSD was induced by KCl micro-injection and its propagation was monitored by recording slow potential changes accompanying CSD. Prostanoid levels in cortical cerebrospinal fluid (CSF) were determined by radioimmunoassay. Pial arteriolar diameter increased significantly from 76 +/- 6 to a maximum of 119 +/- 5 microns (57%, n = 8) for 1.6 +/- 0.1 min when CSD (velocity, 2.8 +/- 0.1 mm/min) reached the cortex just beneath the vessel irrespective of its location. Shortly after CSD expiration from the cortex, pial arteriolar diameter decreased from the pre-CSD level to a minimum of 67 +/- 5 microns (12%, n = 8) for 19.5 +/- 2.1 min. CSD was elicited again in the same animal while the cortical surface under the window was continuously superfused with artificial CSF at a flow rate of 3.2-4.5 ml/min. Pial arteriolar dilation (from 75 +/- 6 to 115 +/- 3 microns, 53 +/- 9%, for 1.6 +/- 0.1 min, n = 8) was observed again during CSD (velocity, 2.7 +/- 0.2 mm/min), however, no constriction of the vessel was seen after CSD expiration. Indomethacin pretreatment (n = 11) to inhibit prostanoid production enhanced the magnitude of CSD-induced vasodilation from the pretreatment levels of 59 +/- 9% (from 82 +/- 5 to 130 +/- 8 microns for 1.7 min) to the post-treatment levels of 82 +/- 13% (from 78 +/- 5 to 142 +/- 12 microns for 1.8 min).(ABSTRACT TRUNCATED AT 250 WORDS)