Nitric oxide inhibition abolishes sleep-wake differences in cerebral circulation

Nitric oxide (NO), being produced by active neurones and also being a cereb ral vasodilator, may couple brain activity and blood flow in sleep, particu larly during active sleep (AS), which is characterized by widespread neural activation and markedly elevated cerebral blood flow (CBF) compared with q uiet wakefulness (QW) and quiet sleep (QS). This study examined CBF and cer ebral vascular resistance (CVR) in lambs (n = 6) during spontaneous sleep-w ake cycles before and after infusion of N-omega-nitro-L- arginine (L-NNA), an inhibitor of NO synthase. L-NNA infusion produced increases in CVR and d ecreases in CBF during all sleep-wake stages, with the greatest changes occ urring in AS (Delta CVR, 88 +/- 19%; Delta CBF -24 +/- 8%). The characteris tic CVR and CBF differences among AS, QS, and QW disappeared within 1-3 h o f L-NNA infusion, but had reappeared by 24 h despite persisting cerebral va soconstriction. These experiments show that NO promotes cerebral vasodilata tion during sleep as well as wakefulness, particularly during AS. Additiona lly, NO is the major, although not sole, determinant of the CBF differences that exist between sleep-wake states.