Nitric oxide inhibition abolishes sleep-wake differences in cerebral circulation.
Nitric oxide (NO), being produced by active neurones and also being a cerebral vasodilator, may couple brain activity and blood flow in sleep, particularly during active sleep (AS), which is characterized by widespread neural activation and markedly elevated cerebral blood flow (CBF) compared with quiet wakefulness (QW) and quiet sleep (QS). This study examined CBF and cerebral vascular resistance (CVR) in lambs (n = 6) during spontaneous sleep-wake 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 decreases in CBF during all sleep-wake stages, with the greatest changes occurring in AS (DeltaCVR, 88 +/- 19%; DeltaCBF -24 +/- 8%). The characteristic CVR and CBF differences among AS, QS, and QW disappeared within 1-3 h of L-NNA infusion, but had reappeared by 24 h despite persisting cerebral vasoconstriction. These experiments show that NO promotes cerebral vasodilatation during sleep as well as wakefulness, particularly during AS. Additionally, NO is the major, although not sole, determinant of the CBF differences that exist between sleep-wake states.
Zoccoli
G
G
Department of Human and General Physiology, University of Bologna, I-40127 Bologna, Italy.
Grant
D A
DA
Wild
J
J
Walker
A M
AM
D000818:Animals; D000831:Animals, Newborn; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001784:Blood Gas Analysis; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D004569:Electroencephalography; D004576:Electromyography; D004585:Electrooculography; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D007262:Infusions, Intravenous; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000008:administration & dosage; D012756:Sheep; D012895:Sleep, REM / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000502:physiology
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase