NITRIC-OXIDE PROMOTES ARTERIOLAR DILATION DURING CORTICAL SPREADING DEPRESSION IN RABBITS

Background and Purpose Pial arterioles transiently dilate during corti cal spreading depression (CSD), although the mechanisms are unclear. W e tested the hypothesis that increased production of nitric oxide (NO) promotes arteriolar dilation. Methods Urethane-anesthetized rabbits w ere equipped with cranial windows, and the diameter (reported in micro meters) of a pial arteriole was determined via intravital microscopy. In each rabbit, a baseline CSD was elicited by microapplication of KCl onto the cortex, and resultant pial arteriolar dilation was measured. Either 100 mu mol/L N-omega-nitro-L-arginine methyl ester (L-NAME) or 50 mu mol/L N-G-nitro-L-arginine (L-NA), both competitive NO synthase inhibitors, was then applied to the brain surface. A CSD was elicited as before. The L-NAME and L-NA were then removed by artificial cerebr ospinal fluid washes. An additional CSD was induced with KCl as before . Results Control CSD in the L-NAME group dilated pial arterioles: bas eline diameter, 66+/-7 mm, with CSD=106+/-8 mm (59% increase). After t opically applied L-NAME, CSD dilated pial arterioles less: baseline di ameter, 61+/-7 mm, with CSD=77+/-6 mm (26% increase), P < .05 compared with control CSD diameter. Topical L-NA had similar effects on CSD: c ontrol CSD dilated pial arterioles 51%; after topical L-NA, only 14% ( P<.05). After removal of L-NAME or L-NA, CSD-induced pial arteriolar d ilation was similar to original control values. Conclusions The revers ible inhibition of CSD-induced pial arteriolar dilation by either L-NA ME or L-NA suggests that NO contributes to arteriolar dilation observe d with CSD.