ARGININE NITRIC-OXIDE PATHWAY AND CEREBROVASCULAR REGULATION IN CORTICAL SPREADING DEPRESSION

Nerve cells release nitric oxide (NO) in response to activation of glu tamate receptors of the N-methyl-D-aspartate (NMDA) subtype. We explor ed the hypothesis that NO influences the changes of cerebral blood flo w (CBF) during cortical spreading depression (CSD), which is known to be associated with NMDA receptor activation. CBF was monitored in pari etal cortex by laser-Doppler flowmetry in halothane-anesthetized rats. Under control conditions, CSD induced regular changes of CBF, which c onsisted of four phases: a brief hypoperfusion before the direct curre nt (DC) shift; a marked CBF rise during the DC shift; followed by a sm aller, but protracted increase of CBF; and a prolonged CBF reduction ( the oligemia). NO synthase inhibition by intravenous and/or topical ap plication of N-G-nitro-L-arginine enhanced the brief initial hypoperfu sion, but the CBF increases and the oligemia were unchanged. L-Arginin e prevented the development of the prolonged oligemia after CSD but ha d no influence on the marked rise of CBF during CSD. Animals treated w ith L-arginine recovered the reduced vascular reactivity to hypercapni a after CSD much faster than control rats. Functional denervation of c ortical and pial arterioles by tetrodotoxin accentuated the pre-CSD hy poperfusion and the oligemia but did not affect the CBF increases. The results suggest that NO is important for the changes of cerebrovascul ar regulation following CSD. The observations may have clinical import ance, since CBF changes during migraine may be triggered by CSD.